IntechOpen

Home > Books > Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods

Open access peer-reviewed chapter

Alternative Approaches to Combat Medicinally Important Biofilm-Forming Pathogens

Written By

Mansab Ali Saleemi, Navindra Kumari Palanisamy and Eng Hwa Wong

Submitted: June 23rd, 2018 Reviewed: July 16th, 2018 Published: November 5th, 2018

DOI: 10.5772/intechopen.80341

Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods IntechOpen
Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods Edited by Sahra Kırmusaoğlu

From the Edited Volume

Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods

Edited by Sahra Kırmusaoğlu

Book Details Order Print

Chapter metrics overview

1,305 Chapter Downloads

View Full Metrics
Advertisement

Abstract

Bacteria have developed the capability to produce structured communities (or cluster of cells) via adherence to surface to form biofilms that facilitate or prolong their survival under extreme environmental condition. Bacterial biomass adheres to inanimate and biotic surfaces in the hospital setting as well as in the environment. In the healthcare system, the biofilm formation on medical devices allows bacteria to sustain as a reservoir and becomes more resistant to antimicrobial agents. However, biofilm formation facilitates pathogens to sabotage the host defenses that are linked to long-term retention within the host cell. Therefore, in this review, we provide some steps leading to the formation of biofilm within the host and on inanimate surfaces, also emphasizing various medically significant pathogens and debate current developments on novel approaches that aimed to prevent biofilm formations and its dispersion to patients.

Keywords

  • biofilm
  • antibiotic resistant
  • distribution
  • control
  • therapeutic strategy

1. Introduction

Biofilm formation is structured accumulation of fastidious microorganisms attached on inanimate objects or compact surfaces that extensively have been examined in the past decades because they particularly cause infections and more often responsible for chronic infections [1, 2, 3]. They are predominantly problematic due to their antimicrobial resistant properties and their ability to evade host defense mechanisms, which substantially hinders disease treatment in the hospital [1, 2, 3, 4]. Bacterial biofilms are ubiquitous in nature and harbor phenotypic adaptations in the environment with respect to broader perspective [1]. The nature of single cell organisms enables them to adhere to each other and form a “complex structure,” which assists to survive under adverse environmental condition. The biofilm formation occurs from planktonic bacteria due to environmental changes and involves in conjugation gene transfer “multiple regulatory network” from one bacterium to another in response to environmental stress [5, 6, 7, 8, 9]. This type of cell-to-cell adhesion and gene transformation changes the expression of surface molecules, virulence factors, and nutrient utilization that enables their survival under unfavorable environmental condition [8, 10, 11, 12, 13, 14, 15, 16, 17].

Bacteria are cocooned within the biofilm and form extracellular matrix, which represents 90% of the biomass [18]. The matrix as a stabilizing scaffold for the three-dimensional structure is composed of extracellular polymeric substance (EPS) along with extracellular DNS and carbohydrate binding protein [19, 20, 21]. Nutrients are trapped by the resident bacteria in the matrix and water is retained efficiently via H-bond interaction with hydrophilic polysaccharides [18, 22]. The composition of extracellular polymeric substance (EPS) is modified in response to alterations in nutrient availability [23, 24] by certain enzyme secretion of bacteria, thus tailoring biofilm formation to the more specific environment [23, 25]. Therefore, the skeletal components of the extracellular matrix are highly hydrated and provide high tensile strength that enables bacteria to exchange their DNA by conjugation and promote cell-to-cell interaction while defending the biomass from predation, radiation, desiccation, oxidizing molecules, and other dangerous agents [18, 26, 27, 28].

The multifaceted nature of biofilms that allow the bacteria to form a community, i.e., division of labor and express their virulence factors in response to local oxygen and nutrient availability, makes them resistant against different antimicrobial agents [29, 30]. Some studies have shown that there are presence of nondividing metabolically inactive recalcitrant bacteria within the biomass [29, 31], which play very crucial role to cause tolerance against broad-spectrum antimicrobial drugs. The matrix protein inside the host cell protects bacterial biofilm against innate immune defenses, i.e., phagocytosis and opsonization [32]. The spread of other virulence factors inside the host cell and drug resistance marker is due to the cell-to-cell interaction [15]. Thus, biofilm-forming pathogens retained and adhere to the infected surface and cause recalcitrant and chronic infection, i.e., upper respiratory tract infection (particularly, Pseudomonas aeruginosa) [33, 34], dental decay (mixed culture of Streptococcus mutans, and other pathogens) [35], ventilated-induced and other device-associated infections (Escherichia coli, Klebsiella spp., Enterococcus faecalis, Staphylococcus aureus, etc.) [36, 37], urinary tract infections [Proteus spp., uropathogenic E. coli (UPEC)] [38]. In particular, immunocompromised patients are the most common target to all these biofilm-forming pathogens, causing a devastating impact on patients, and in many cases, leading to death. Here, we analyze the formation of intracellular and extracellular biofilm which is the underlying factor for various medically important microorganisms. Given the recalcitrance and prevalence of infections caused by biofilm-forming pathogens, we discuss knowledge about the most current progresses in the advancement of novel strategies of biofilm.

Advertisement

2. Extracellular formation of biofilm

2.1 Bacterial attachment on surfaces and what does make it adhere to object surface?

Bacterial biofilm growth, subsequent maturation, and aggregation consist of irreversible and reversible stages, which involve various conserved and species-specific aspects. At the first stage, the bacteria are introduced on the surface; a process of at least a part of stochastic that is driven by gravitational forces and Brownian motion, and usually influenced by nearby hydrodynamic forces [39, 40]. Microorganisms encounter with repelling or attractive forces—within the niche that alter depending on ionic strength, pH, nutrient levels, and temperature. Bacterial cell wall composition, along with medium properties, affects direction and velocity toward or away by the contact surface of pathogens [39]. Motile bacteria utilize flagella in order to overcome repulsive and hydrodynamic forces, by having a competitive advantage. The main function of flagella is to provide motility and initial cell attachment to the surface for various pathogens, including Listeria monocytogenes, E. coli, Vibrio cholerae, and P. aeruginosa [41, 42, 43, 44, 45]. In some species of bacteria, chemotaxis plays very important role in direct attachment to nutrient composition, for instance, mutations arise in CheR1 methyltransferase, which have been observed to vary the response of amino acid of P. aeruginosa and impair maturation of bacterial biofilm and attachment [46]. Some earlier studies have been shown that chemotaxis in E. coli is dispensable [5]; moreover, current observations revealed that the disruption occurs in the chemotaxis methyl accepting protein II and informs biofilm defects particularly in uropathogenic E. coli cells [47]. With respect to intercepting surface, bacterial attachment is facilitated by additional secreted molecules such as adhesin protein and extracellular adhesive appendages.

Initially, the attachment is reversible and dynamic during which pathogens can separate and rejoin planktonic biomass if agitated through repulsive forces [48], hydrodynamic forces—detach bacteria off from the surface. Some bacteria attained irreversible attachment in order to maintain a firm grip on the cell surface. Serotypes of other E. coli and uropathogenic E. coli depend intensely on the type 1 pili [5, 40, 49, 50, 51]. Uropathogenic E. coli harbors several pili systems (means CUP system), which mediate adhering to a specific niche [38]. Attachment on the bacterial surface is facilitated by the adhesion protein (FimH), which identifies mannosylated moieties [50, 51, 52]. The adhesive protein (FimH) plays a critical role in the pathogenesis of uropathogenic E. coli because it facilitates adherence and causes invasion to epithelial cells of bladder in human, adheres to the human uroplakin and is also critical in preclinical murine cystitis model, which causes human disease [51, 53, 54]. FimH is much more consistent to play a critical role in the virulence of human disease under positive selection [52, 53, 54, 55, 56].

Furthermore, antigen 43, curli fibers, and type 1 pili have been observed to facilitate attachment and cell-to-cell interaction on inanimate surfaces [57]. Curli fiber also mediates attachment to the extracellular matrix components in eukaryotes such as plasminogen, fibronectin, and laminin [58]. Pseudomonas aeruginosa, for instance, uses various additional organelles, which assist in adherence to the surface, irreversibly. Contrary to UPEC and P. aeruginosa, Gram-positive bacteria (Enterococci) are lactose producing, nonmotile, and recently identified to contain nonadhesive (pili) that mediate attachment to the extracellular matrix components in eukaryotes. Examples of these include Ace (E. faecalis) and SagA (E. faecium), which attach to the collagen protein [59] and surface protein (Esp). This has been observed to stimulate abiotic formation of biofilm on the contact surface specifically in E. faecalis [60]. Current studies showed the existent of biofilm-associated pili (Ebp) and also confirmed their contribution toward urinary tract infections, endocarditis, and biofilm formation and attachment [61].

2.2 Maturation of biofilm

Cell-to-cell interaction triggers specific intrinsic responses that cause changes in the gene expression, upregulating factors favorable to sessility especially for those involved in extracellular matrix protein formation [40]. However, relatively very little information is obtained about the matrix constituents with respect to E. coli pathogen. Initially, cellulose was recognized as essential components in E. coli pellicle biofilms and later on expressed with curli fibers in gastrointestinal E. coli strains [62]. Curli fiber plays a critical role in pellicles, for instance, curli fiber (amyloid) that leads to the pellicle biofilm formation. It also acts as a curlicide to prevent pellicle formation, and some of them have deficient to form pellicles (known as curli mutants) [63]. Further studies revealed that colonic acid and polyglucosamine (PGA) take part in biofilm architecture [64], while the PGA being predominant among the clinical strains, particularly in UPEC isolates. Thus, more detailed investigations are required for further characterization of extracellular matrix protein in E. coli. The composition of extracellular matrix protein has been extensively analyzed in P. aeruginosa and varies depending on external environmental conditions [65]. The primary components of EPS are Psl and Pel [25]. Psl enhances the attachment of P. aeruginosa to epithelial cells [66] and mucin, while the expression of Pel increased in small colony variants (SCV) isolated from the cystic fibrosis patients associated with Pseudomonas persistence in the airways of lung [67]. Moreover, intercellular interactions and biofilm stabilizations in P. aeruginosa are critical in response to environmental DNA (eDNA) [68].

Mature P. aeruginosa biofilm formations are more resistant to treatment with DNase as compared to young biofilms, demonstrating that eDNA remains stable because the components of EPS are not abundant during the initial stage of biofilm when the bacterial cells come to attach each other. In contrast, the concentration of eDNA increases during biofilm maturation stage due to the occurrence of bacterial cell lysis in response to quorum sensing mechanism of Pseudomonas quinolone signal (Pqs) [69]. In Pseudomonas, type IV pili play an essential role in the migrating pathogens to form aggregation in the area of high eDNA binding attraction [70]. The amount of eDNA to form biofilm structure has already been observed in E. faecalis. Some reports identified that biofilm formation in this organism is influenced by the affected autolysis of cells and intracellular release of DNA [71, 72]. Initial study reported that the mutant reduced the biofilm formation by 30% due to the lack of autolysin gene, Atn [59]. In another study investigated, it showed that specific stage of bacterial biofilm formation required temporal regulation by Atn for the release of DNA [73].

2.3 Matrix escape mechanisms

Bacterial mature biofilm provides a suitable living environment to the resident microorganisms for making compact surface adherence community, so as to share products and actively exchange their genetic materials by conjugation. Moreover, as biofilms mature, dispersal becomes a choice. In addition to passive dispersal caused by shear stress, the pathogen develops different ways to recognize environmental changes, which make it to stay within the biofilm. Bacterial biofilm dispersal occurs as a result of various clues such as oxygen fluctuations, modifications in nutrient availability, and increases in toxic products [74]. Biofilm dispersal is induced by the increase of extracellular iron in uropathogenic E. coli [75], while in Pseudomonas spp., it is due to the increased quantities of various nitrogen and carbon source [76]. The amounts of small molecules such as alterations in environment and changes in gene expression are monitored by various sensory systems [77]. Among various other signals, for instance, universal cyclic-di-GMP has been used in P. aeruginosa and E. coli causing implication in a shift between motility and sessility. Typically, an increase in the level of cyclic-di-GMP is favorable to sessility, while a reduction in cyclic-di-GMP induces upregulation of motility [78].

Recently, some results reported the factors responsible for such changes such as downregulation of extracellular polymeric substance, reduction of cyclic-di-GMP in bacterial biofilm communities, and upregulation of swarming and swimming motility [25]. Certain type of enzymes (such as alginate lyase) also participates in pathogen detachment from surface especially in P. aeruginosa [79], whereas in E. coli, the enzyme (CsrA) is responsible to repress the synthesis of PGA [80]. Along with that downregulation of EPS, certain molecules of surfactant are produced causing a reduction in cell-to-cell interaction. Moreover, studies identified that flagellated populations within the biofilms of P. aeruginosa migrate to other void surface in order to make colonies [65]. Initially, these colonies loosely attach to compact surface, but after maturation process, they make a hard shell in the surrounding and use the infected surface as a source of nutrient. Sometimes, live cells use dead cells as a source of carbon. When bacteria become dead, then live cells accumulate on it, bind to each other by sharing their genetic materials and form a compact layer that is usually very hard to break. Dead cells are also responsible for creating cavity within the bacterial biomass. The bacteria within the biofilm can be scattered by applying dispersal mechanism.

Due to dispersing nature of bacteria, they may have the ability to restart the biofilm formation process after encountering a favorable environmental condition [81]. This is another sophisticated mechanism of dispersal revealed by using B. subtilis, which could be prevalent among the bacterial species. Researchers reported that the pathogen (B. subtilis) lost its cellular integrity within 5–8 days and also found that disassembly of biofilm is associated with a mixture of different amino acids (D-tyrosine, D-methionine, etc.) that are formed during bacterial stationary growth phase [82]. These D-types of amino acids interfere with bacterial attachment to cell surface and perturbation to fiber dissociation, without influencing matrix component expression or bacterial growth [83]. In B. subtilis, the performance of biofilm is disrupted by the addition of D-type amino acid mixture [83]. Further studies showed that another factor such as norspermidine, which is produced by B. subtilis, works together with D-type amino acid leading to biofilm disassembly [84]. So, this type of association—norspermidine/D-type amino acid—is essential for the eradication of bacterial biofilm and makes them vulnerable to antimicrobial agents used in the hospital.

Advertisement

3. Bacterial intracellular biofilms

Gathering evidence have showed that numerous bacterial pathogenic species formerly considered as extracellular can retain within the host cell by adapting intracellular bacterial lifestyle that includes the bacterial communities having biofilm-like properties. First, a murine model of infection was used to assess the bacterial communities for UPEC [85]. Type 1 pili in uropathogenic E. coli bind to the receptor on superficial bladder cells [86], triggering to induce bacterial internalization. Toll-like receptor-4 (TLR-4)-dependent process used to expel out from inside the UPEC [87], but certain bacteria elude exocytic procedure and leave out from the cytoplasm of host cell, where they duplicate into intracellular bacterial communities (IBCs) [85]. Several developmental stages lead to the process of IBCs that indicate distinct morphological features [85]. After passing first 6 h ensuing bladder inoculation, UPEC rapidly divides (replication time 30–35 min) causing small clusters associated with loosely attached rods (during early IBCs), having a coccoid shape and an average bacterial length of about 0.7 mm. The bacterial exponential growth rate dramatically drops between 6 and 8 h, exceeding replication time to 60 min. This is the second stage where bacteria accumulate and are tightly packed within the biofilm and organized a compact sphere-shaped structure (mature-stage IBCs) (Figure 1).

Figure 1.

Schematic diagram of the development of IBC cascade in uropathogenic E. coli (UPEC), taken by scanning electron microscope (SEM) images indicating different structural changes from attachment to dispersion and fluxing.

The amount of IBCs is found between 3 and 700 in an infected patient’s bladder—IBCs are composed of 104–105 bacterial cells [88]. There are numerous fibers surrounded on IBC bacteria that originate from the surface of pathogen and enclose pathogens in individualized sections. One of the main components present on the surface of IBCs called polysaccharide (sialic acid) that provides protection from the attack of immune system and environmental stress. The heterogeneous nature of IBCs, such as extracellular bacterial biofilm, composed of different subpopulation having distinct gene expression systems [89]. As IBCs expand, they induce the bacterial biofilm to cause interruption against cell membrane of host, producing a pod-like structure on the infected cell surface. Ultimately, UPEC detaches as filament or single rod at the IBC boundary and the infected cells are flux out into the lumen of bladder where can invade epithelial cells and restart the process through binding [85]. The inhibitor (SuIA) of cell division has been observed to be crucial for dispersal and filamentation of UPEC from the bacterial biofilm. The patients suffered from urinary tract infections (UTIs) are more likely observed with the UPEC filaments in their urine, but not in comparison with healthy controls [90].

The formation of IBC is prevented by intense molecular blockages and during acute infection—development of chronic cystitis—the IBC numbers are higher, representing the significance of intracellular pathways in the pathogenesis of UTIs [88]. The cycle of IBC is dependent on FimH, causing interruption in the expression of type-1 pili after invasion to host cell, and disrupts normal development of IBC due to attenuation of UPEC [54]. The two-component system (QseBC) is a key factor influencing curli expression, formation of IBC and type-1 pili. Some studies indicated that the intracellular pathway of UPEC is necessary for the TCA cycle completion [47]. The techniques such as qPCR and DNA microarray analyses interpreting the UPEC expression patterns within IBC pathogen exposed that acquisition of iron in bacteria is upregulated, representing the significance of system biomass formation [91]. While in clinical isolates of UPEC, the iron acquisition patterns are prevalent [92]. Moreover, the pathogen Klebsiella pneumoniae is more commonly seen in community- and hospital-acquired infection. About up to 5% forms intracellular communities and is more predominant in hospitalized diabetic patients [93]. Likewise to UPEC, the Klebsiella pneumoniae invasion is mediated by type-1 pili and formation of IBC, although the differences occur in the expression kinetic of pili and filaments [90]. The ability to occupy an intracellular niche and persist within the host cell through transitioning from single microbial cell to the multicellular community is not confined to uropathogens. Researchers showed that by using different animal models and cell line of acute lung infection, the cluster formation occurs inside the lung airways due to P. aeruginosa, morphology similar to Klebsiella and UPEC (IBCs) [94]. The biofilm formation ability could be evolutionary adaptation of pathogens that enable the bacteria to persist within the host cell. All these findings represent the formation of IBC, a process that enables the bacteria to rapidly expand inside the host cell and take part in bacterial persistence.

Advertisement

4. Postantibiotic period: treatment strategy for biofilm

Broad-spectrum antibiotics are the drug of choice for the treatment of bacterial infections. Conventional antibiotics act as either killing the bacterial cell (bactericidal) or inhibiting the cell division (bacteriostatic). Numerous evidence shows that the use of antibiotics extensively causes damage to the host microbiota, producing a condition where invading bacteria can prevail and enhance the selective pressure against drug resistance [95]. Furthermore, surgery proceeded by administering antibiotics is highly successful in order to minimize the infection prophylactically. In certain cases, the perfect treatment of choice for foreign material associated with biofilm infections is the removal of infectious device. In some cases like pacemakers, cardiac implants and implantable prostheses, device removal is difficult [37]. Biofilm formation nature of bacteria that make them recalcitrant against different antimicrobial drugs is a result of prolonged treatment. There is a need for the irradiation or complete removal of these kinds of pathogens. Antibiotic resistance is not only due to increased resistance markers transmitted within the bacterial biofilm community, but also due to high metal ion concentration, low pH, and the presence of persistent cells that are metabolically inactive and inactivate the antibiotics [31]. All these characteristics make bacterial biofilm more tolerant/resistant to antimicrobial drugs up to 1000-fold more when compared to planktonic bacterial cells [96]. Therefore, an alternative strategy must be investigated to combat the antibiotic resistant strains and make them vulnerable to antimicrobial drugs. Here below, we have mentioned some of the recent developments in strategies that are considered to prevent formation of biofilm by bactericidal mechanism or targeting distinct developmental stages of biofilm (Figure 2).

Figure 2.

Schematic diagram about the different stages in the development of biofilm and indicating the strategies to preventing and damaging the bacterial biofilm production at particular stages.

Advertisement

5. Bacterial killing strategies

5.1 Elimination of foreign material (indwelling devices) and abscess

There are studies that have reported that the presence of any foreign body (indwelling medical devices such as implants or prostheses or catheters) in low inoculums of Staphylococcus aureus (102 CFU/ml) in animal tissues was sufficient to form abscesses in the patients (95%) despite significant existence of leukocytes. In fact, this could be associated with the existence of any foreign material considerably intracellular bactericidal effects of body immune cells (leukocytes) and downregulated the mechanism of phagocytosis [97]. The polymorphonuclear leukocytes cannot perform well in the presence of any foreign body because it provides a surface ideal for the bacterial attachment. Therefore, the existence of any foreign material considerably increases the chances of bacterial biofilm formation. This leads to the pathogen becoming more persistent and resistant against conventional antibiotics. Thus, potential therapeutic strategy is required for the elimination of such type of bacterial biofilm formations. Certain precautionary measures could be employed, for instance, to replace the infected devices used for medical purposes in the patients with a new one. Otherwise, it would be hard to overcome the problem regardless of applying various effective antimicrobial drugs in response to fastidious pathogens. Changing dialysis catheter if it is infected by the pathogens is another measure that could be taken. When pathogen forms biomass on the catheter, it could be the source of bacterial colonization leading to bacteremia which may be caused by a deadly bacterial strain. For the cure of catheter-associated infections caused by bacterial biofilm formation, it is important to change the catheter infected with pathogens along with administration of antibiotic intravenously during a short time in order to eradicate the pathogen before it invades into the bloodstream. However, in some cases, it is hard to change the catheter temporarily; therefore, antimicrobial drugs and other alternative therapy may be the best option for the minimal release of pathogens from the infected site.

5.2 Phage therapy

An alternative approach to antibiotic treatment is phage therapy [98]. Phages are present in a wide range in the environment. It can be isolated easily and ubiquitous in nature. Their host ranges from specific to narrow, they are able to self-replicate, and therefore, a small dosage may be sufficient to disturb the host microorganisms. Furthermore, high mutation rate of phage facilitates adaptation as conforming bacterial host aggregate mutations to fix in a specific environment. Phage therapy has various advantages during lytic cycle phage that does not enter prophage cycle and rarely transfers or contains a virulence gene, thus causing destruction of bacterial cell rapidly. Many phages are associated with EPS degrading protein [99] or spread during stationary growth phase; these features allow to persist inside the bacterial biofilm [100].

5.3 Antimicrobial peptides

This is another alternative approach used for the improvement of new type of antimicrobial drug, usually produced by innate immune response mechanism [101]. Contrary to that, their mechanism of action and antimicrobial spectrum activity must be defined more accurately before applying as a therapeutic strategy. Cathelicidin, for instance, possesses most essential type of antibacterial peptides. The biofilm formation of multidrug-resistant Pseudomonas strains, isolated from cystic fibrosis (CF) patients, is reduced considerably by BMAP-28, BMAP-27, and BMAP-29 [102]. According to a recent study by Pompilio et al. [102], antimicrobial activity of tobramycin against multidrug-resistant strains is less than cathelicidin peptides. This study indicates that the multidrug-resistant strains are vulnerable to cathelicidins due to antibiofilm agents. Another important group that can be used to assess the inhibitory effects is called lytic peptides. These peptides assist in attachment of lipopolysaccharides (LPS) to the cell membrane of pathogen and cause cell membrane disruption. The study on Staphylococcus aureus indicated that in vitro formation of biofilm is prohibited by the lytic peptide (PTP-7) and easily penetrates the bacterial biofilm causing death of the bacteria at a rate of 99.9%. This peptide has the capacity to bear extreme acidic environment and inhibit the biofilm formation of Staphylococcus aureus [103].

5.4 Silver nanoparticles

Many researchers have done research on the antimicrobial property of silver nanoparticles. Fey [37] found that the silver nanoparticles are the best alternative strategy to combat the bacterial biofilms. For example, antimicrobial agents (silver nanoparticles) have been incorporated with medical devices and have showed to inhibit the device-associated bacterial biofilms. Silver was frequently used as an antimicrobial agent for different pathogens over a 100 years; for instance, during World War 1, it was extensively used to sterilize the wound infections [104]. The antimicrobial activity of silver nanoparticles depends on the positively charged ions of metal and electrostatic interactions between negatively charged cell membrane of bacteria [105]. The thiol group in silver is the main cause of death in bacteria that play an important role in the inactivation of enzyme [106]. This is the reason why silver nanoparticles are increasingly used in response to various bacterial infections. The antimicrobial agents contain different properties such as high aspect ratios, nonimmunogenic, biocompatible, nonbiodegradable, ultralight weight, and easy cell membrane penetration. Due to such remarkable properties, we can apply silver nanoparticles in various applications such as infection therapy, gene therapy, and as antioxidants. The size of silver nanoparticles is typically smaller than 100 nm. The mechanism of action of silver nanoparticle is to interrupt the cell membrane of bacteria, generate the reactive oxygen species (ROS), interrupt the metabolic pathway, prevent the replication of DNA, disrupt the bacterial electron transport chain (ETC) [106], and release the toxic ions outside the bacterial cells that lead to the death of bacteria. There are large numbers of studies conducted regarding toxicity mechanism of silver nanoparticles in rabbits. There is a study that showed that silver nanoparticles inhibited bacterial biofilm formation against Staphylococcus aureus, without accumulating inside the host tissue [106, 107].

5.5 Polysaccharides

Bacterial cell-to-cell interaction mediated by the exopolysaccharides is a serious threat to the formation of biofilm and stabilization. Mutants incapable to export or synthesize such exopolysaccharides are usually deficient in the formation of biofilm and adherence and hence are extremely sensitive to killing through host immune defenses and antimicrobial drugs [108]. Recent studies showed that certain bacterial exopolysaccharides destabilize or prevent biofilm formation by some pathogenic species. For instance, the existence of Pseudomonas aeruginosa prevented biofilm formation of S. epidermidis in in vitro experiments [109]. Polysaccharides along with nonbactericidal antibiofilm characteristics have been separated from acellular biofilm (or biomass) extracts of various species [108]. The antibiofilm properties of Pseudomonas aeruginosa have the ability to act as signaling molecules that effect the expression of genes in susceptible pathogens, change the physical features of isolated bacterial cells, and prevent the protein-carbohydrate interactions. Most polysaccharides with antibiofilm properties allow a broad-spectrum inhibition of biofilm, while some are proficient of scattering preformed biofilms. So far, there are evidence suggests that polysaccharide with antibiofilm features acts as a surfactant molecule that alters the physical properties of abiotic surfaces and bacterial cells. Some results also show that polysaccharides might modulate the expression of genes of the recipient pathogenic bacteria by acting as signaling molecules [110]. Another potential mode of action of polysaccharide is to prevent competitively the multivalent protein-carbohydrate interactions [66]. As a result, polysaccharides with antibiofilm properties might block tip adhesins of pili and fimbriae, or block sugar or lectin-binding proteins that are present on the outer surface of pathogens. In pathogen P. aeruginosa, for instance, lectin-dependent adhesion to human cell is proficiently repressed by galactomannans [111]. This kind of polysaccharides that inhibit the biofilm could be a prominent strategy appropriate for the prevention of bacterial infections. Some scientist showed that antibiofilm polysaccharides can be used as an adjuvant because of enhancing antibiotic drug functions [108].

5.6 Interference with signal transference

Many studies have been carried out on biofilm inhibition caused by interruption of the pathogen signaling cascades. This is possible provided that the two-component systems in bacteria establish a dominant means of translating and intercepting the environmental changes. Signal transduction inhibition system plays a critical role in response to antimicrobial therapy because of this type of signaling cascade interruption. Not only does it kill the pathogen, but it also interferes with the gene expression. Two-component system (QseBC) is the best alternative candidate for targeting the drugs, particularly in Gram-negative biofilm-forming pathogens [112]. QseC/QseB establishes a significant association between the bacterial environmental signaling and the host stress response. The pathogen (E. coli) responds to autoinducer-3 in the intestine that is formed by the human stress hormones (such as epinephrine and norepinephrine) and gut flora. The cascade of signaling transduction comprises chemotaxis by activation of QseC and by using the serine receptor Tsr. In the quest for novel antimicrobial drugs and therapeutic targets, two-component system (QseBC) can play an important role to inhibit biofilm formation by blocking the binding of epinephrine or norepinephrine to QseC, as a result to reduce QseB/QseC signaling and decrease virulence and motility [113]. Studies have also suggested that the removal of QseC in EHEC and UPEC causes an excessive activation of response regulator QseB, owing to particular QseC phosphatase activity required for deactivation of QseB. The optimal strategy behind targeting the phosphate activity is to interfere with common gene expression in QseC containing pathogens [47]. Some other studies focused on the FsrATC/FsrA inhibitors in E. faecalis. The expression of gelE-sprE and FsrBDC control by the FsrC/FsrA leads to increase in the production of serine protease and gelatinase, both are crucial for the proper eDNA production [71].

5.7 Antimatrix agents

Apart from that, extracellular matrix with disrupting components is also very important to target the bacterial aggregates. Various observations exploited the inhibiting enzymes potentially involved in the modification or synthesis of cell wall-secreted or associated with EPS components. In these studies, use of engineered or naturally occurring enzyme and use of phage therapy as an enzyme delivery vehicle or to interrupt with matrix integrity by taking benefits from metal chelators have been recommended.

5.8 Chelating agents

Metal cations such as iron, magnesium, and calcium have been associated with stabilizing the matrix integrity [114]. Chelating agents indicated to cause interruption in the bacterial cell membrane stability besides disrupting the bacterial biomass structure [39]. In vitro study showed that biofilm formation was inhibited in various Staphylococcus species by sodium citrate [115]. Furthermore, eradication of bacterial biofilms in in vitro experiments is also facilitated by tetrasodium EDTA, while disodium EDTA only reduced the bacterial biofilm formations in P. aeruginosa and Staphylococcus species [116]. Current reports suggested that the solution of minocycline-EDTA was used to inhibit indwelling catheter-associated infections especially in children. There were no adverse side effects observed in patients treated with the solution of minocycline-EDTA but only a limited number (21%) of untreated group (control) developed infections [117]. Moreover, in hemodialysis patients, catheter-associated bloodstream infections were observed after applying minocycline-EDTA [118].

5.9 Enzyme

The main mechanism of active dispersal of bacterial biofilm is through the formation of extracellular enzymes (proteins) that act on several structural components (such as exopolysaccharides, surface proteins, and extracellular DNA) of the extracellular polymeric substances. These enzymes play an important role in the cell separation from the bacterial biofilm colonies and facilitate their planktonic discharge into the environment [119]. Through purifying and isolating these enzymes, therapist can apparently add them to preformed bacterial biofilms exogenously at raised concentrations, in order to make biofilm-associated bacteria more susceptible to antimicrobials/antibiotics and to achieve interventional dispersal of biofilms. For this purpose, several classes of enzymes (specifically proteases, glycoside hydrolases, and deoxyribonucleases) have been explored for the eradication of bacterial biofilms [119]. The enzymes dispersin-B and DNase-I have gained greater attention as possible antibiofilm agents, especially in response to Gram-positive bacteria. The DNase effect depends on its capability to interrupt the eDNA that is established within the bacterial biomass structure [73]. The treatment of DNase prevents biofilm formation in Enterococcus and Staphylococcus and dispersed bacterial biofilm [73]. For the treatment of patients with cystic fibrosis (CF), a recombinant enzyme (pulmozyme) is used in some cases [37]. However, treatment with dispersin-B represented to be more effective in response to S. aureus and S. epidermidis [77]. In vitro studies indicated that engineered dispersin-B used bacteriophage machinery in order to replicate during the stationary phase of cell growth, hence causing disruption of complete E. coli biofilms [120].

Advertisement

6. Conclusion

Currently, the removal of bacterial biofilm is the most challenging task for the clinicians and microbiologists. Antibiotics are not the best choice for the treatment of infections caused by bacteria forming biofilm. Biofilm formation allows the pathogen to adhere to the host surface under extreme condition and is resistant against a wide range of antibiotics. The choice of drug depends on the characteristics of the biofilm such as composition, age, solidity, and type of pathogens. These are the major components influencing the microbial susceptibility. As the bacterial biofilm matures, it enhances the accumulation of exopolymeric substance (EPS), attaches with the oxygen and nutrient gradients that effect bacterial growth rates and metabolism of cells, becomes impermeable, and reduces the activity of antimicrobial agents. This leads to resistance to most antibiotic regime. Therefore, novel potential therapeutic strategies should be considered to curb bacterial biofilm formation at specific stage without harming the pathogen. Antiadhesion and antimatrix agents are exciting strategies that may be used pending further investigation. Advertisement

List of abbreviations

EPS

extracellular polymeric substance

DNS

deoxyribonuclease

CBP

carbohydrate-binding protein

DNA

deoxyribonucleic acid

CUP

chaperone-usher pathway

UPEC

uropathogenic E. coli

PGA

polyglucosamine

SCV

small colony variants

eDNA

environmental deoxyribonucleic acid

PQS

Pseudomonas quinolone signal

c-di-GMP

cyclic di-GMP

AL

alginate lyase

BS

Bacillus subtilis

TLR-4

toll-like receptor-4

IBC

intracellular bacterial communities

UTIs

urinary tract infections

SEM

scanning electron microscope

TCA

tricarboxylic acid

qPCR

quantitative polymerase chain reaction

HAIs

hospital-acquired infections

CFU

colony forming unit

MDR

multidrug resistant

LPS

lipopolysaccharides

ETC

electron transport chain

ROS

reactive oxygen species

EHEC

enterohemorrhagic E. coli

EDTA

ethylene-diamine-tetra-acetic acid

CF

cystic fibrosis

References

  1. 1. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: From the natural environment to infectious diseases. Nature Reviews. Microbiology. 2004;2:95-108
  2. 2. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: A common cause of persistent infections. Science. 1999;284:1318-1322
  3. 3. O’Toole G, Kaplan HB, Kolter R. Biofilm formation as microbial development. Annual Review of Microbiology. 2000;54:49-79
  4. 4. Kolter R. Biofilms in lab and nature: A molecular geneticist’s voyage to microbial ecology. International Microbiology. 2010;13:1-7
  5. 5. Pratt LA, Kolter R. Genetic analysis of Escherichia coli biofilm formation: Roles of flagella, motility, chemotaxis and type I pili. Molecular Microbiology. 1998;30:285-293
  6. 6. Prigent-Combaret C, Brombacher E, Vidal O, Ambert A, Lejeune P, Landini P, et al. Complex regulatory network controls initial adhesion and biofilm formation in Escherichia coli via regulation of the csgD gene. Journal of Bacteriology. 2001;183:7213-7223
  7. 7. Parsek MR, Singh PK. Bacterial biofilms: An emerging link to disease pathogenesis. Annual Review of Microbiology. 2003;57:677-701
  8. 8. Lenz AP, Williamson KS, Pitts B, Stewart PS, Franklin MJ. Localized gene expression in Pseudomonas aeruginosa biofilms. Applied and Environmental Microbiology. 2008;74:4463-4471
  9. 9. Monds RD, O’Toole GA. The developmental model of microbial biofilms: Ten years of a paradigm up for review. Trends in Microbiology. 2009;17:73-87
  10. 10. Whiteley M, Bangera MG, Bumgarner RE, Parsek MR, Teitzel GM, Lory S, et al. Gene expression in Pseudomonas aeruginosa biofilms. Nature. 2001;413:860-864
  11. 11. Stanley NR, Britton RA, Grossman AD, Lazazzera BA. Identification of catabolite repression as a physiological regulator of biofilm formation by Bacillus subtilis by use of DNA microarrays. Journal of Bacteriology. 2003;185:1951-1957
  12. 12. Schembri MA, Kjaergaard K, Klemm P. Global gene expression in Escherichia coli biofilms. Molecular Microbiology. 2003;48:253-267
  13. 13. Bagge N, Hentzer M, Andersen JB, Ciofu O, Givskov M, Hoiby N. Dynamics and spatial distribution of beta lactamase expression in Pseudomonas aeruginosa biofilms. Antimicrobial Agents and Chemotherapy. 2004;48:1168-1174
  14. 14. Beloin C, Valle J, Latour-Lambert P, Faure P, Kzreminski M, Balestrino D, et al. Global impact of mature biofilm lifestyle on Escherichia coli K-12 gene expression. Molecular Microbiology. 2004;51:659-674
  15. 15. Vuong C, Voyich JM, Fischer ER, Braughton KR, Whitney AR, DeLeo FR, et al. Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system. Cellular Microbiology. 2004;6:269-275
  16. 16. Zhang L, Mah TF. Involvement of a novel efflux system in biofilm-specific resistance to antibiotics. Journal of Bacteriology. 2008;190:4447-4452
  17. 17. Klebensberger J, Birkenmaier A, Geffers R, Kjelleberg S, Philipp B. SiaA and SiaD are essential for inducing auto aggregation as a specific response to detergent stress in Pseudomonas aeruginosa. Environmental Microbiology. 2009;11:3073-3086
  18. 18. Flemming HC, Wingender J. The biofilm matrix. Nature Reviews. Microbiology. 2010;8:623-633
  19. 19. Tielker D, Hacker S, Loris R, Strathmann M, Wingender J, Wilhelm S, et al. Pseudomonas aeruginosa lectin LecB is located in the outer membrane and is involved in biofilm formation. Microbiology. 2005;151:1313-1323
  20. 20. Branda SS, Chu F, Kearns DB, Losick R, Kolter R. A major protein component of the Bacillus subtilis biofilm matrix. Molecular Microbiology. 2006;59:1229-1238
  21. 21. Diggle SP, Stacey RE, Dodd C, Camara M, Williams P, Winzer K. The galactophilic lectin, LecA, contributes to biofilm development in Pseudomonas aeruginosa. Environmental Microbiology. 2006;8:1095-1104
  22. 22. Conrad A, Suutari MK, Keinanen MM, Cadoret A, Faure P, Mansuy-Huault L, et al. Fatty acids of lipid fractions in extracellular polymeric substances of activated sludge flocs. Lipids. 2003;38:1093-1105
  23. 23. Sauer K, Cullen MC, Rickard AH, Zeef LA, Davies DG, Gilbert P. Characterization of nutrient-induced dispersion in Pseudomonas aeruginosa PAO1 biofilm. Journal of Bacteriology. 2004;186:7312-7326
  24. 24. Gjermansen M, Ragas P, Sternberg C, Molin S, Tolker Nielsen T. Characterization of starvation-induced dispersion in Pseudomonas putida biofilms. Environmental Microbiology. 2005;7:894-906
  25. 25. Ma L, Conover M, Lu H, Parsek MR, Bayles K, Wozniak DJ. Assembly and development of the Pseudomonas aeruginosa biofilm matrix. PLoS Pathogens. 2009;5:e1000354
  26. 26. Walters MC 3rd, Roe F, Bugnicourt A, Franklin MJ, Stewart PS. Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Antimicrobial Agents and Chemotherapy. 2003;47:317-323
  27. 27. Jefferson KK, Goldmann DA, Pier GB. Use of confocal microscopy to analyze the rate of vancomycin penetration through Staphylococcus aureus biofilms. Antimicrobial Agents and Chemotherapy. 2005;49:2467-2473
  28. 28. Mai-Prochnow A, Lucas-Elio P, Egan S, Thomas T, Webb JS, Sanchez-Amat A, et al. Hydrogen peroxide linked to lysine oxidase activity facilitates biofilm differentiation and dispersal in several gram-negative bacteria. Journal of Bacteriology. 2008;190:5493-5501
  29. 29. Lewis K. Persister cells and the riddle of biofilm survival. Biochemistry (Mosc). 2005;70:267-274
  30. 30. Domka J, Lee J, Bansal T, Wood TK. Temporal gene expression in Escherichia coli K-12 biofilms. Environmental Microbiology. 2007;9:332-346
  31. 31. Lewis K. Multidrug tolerance of biofilms and persister cells. Current Topics in Microbiology and Immunology. 2008;322:107-131
  32. 32. Cerca N, Jefferson KK, Oliveira R, Pier GB, Azeredo J. Comparative antibody-mediated phagocytosis of Staphylococcus epidermidis cells grown in a biofilm or in the planktonic state. Infection and Immunity. 2006;74:4849-4855
  33. 33. Koch C, Hoiby N. Pathogenesis of cystic fibrosis. Lancet. 1993;341:1065-1069
  34. 34. Govan JR, Deretic V. Microbial pathogenesis in cystic fibrosis: Mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiological Reviews. 1996;60:539-574
  35. 35. Kuramitsu HK, Wang BY. The whole is greater than the sum of its parts: Dental plaque bacterial interactions can affect the virulence properties of cariogenic Streptococcus mutans. American Journal of Dentistry. 2011;24:153-154
  36. 36. Venditti M, Biavasco F, Varaldo PE, Macchiarelli A, De Biase L, Marino B, et al. Catheter-related endocarditis due to glycopeptide-resistant Enterococcus faecalis in a transplanted heart. Clinical Infectious Diseases. 1993;17:524-525
  37. 37. Fey PD. Modality of bacterial growth presents unique targets: How do we treat biofilm-mediated infections? Current Opinion in Microbiology. 2010;13:610-615
  38. 38. Foxman B. The epidemiology of urinary tract infection. Nature Reviews. Urology. 2010;7:653-660
  39. 39. Donlan RM. Biofilms: Microbial life on surfaces. Emerging Infectious Diseases. 2002;8:881-890
  40. 40. Beloin C, Roux A, Ghigo JM. Escherichia coli biofilms. Current Topics in Microbiology and Immunology. 2008;322:249-289
  41. 41. Toutain CM, Caizza NC, Zegans ME, O’Toole GA. Roles for flagellar stators in Biofilm formation by Pseudomonas aeruginosa. Research in Microbiology. 2007;158:471-477
  42. 42. Lemon KP, Higgins DE, Kolter R. Flagellar motility is critical for Listeria monocytogenes biofilm formation. Journal of Bacteriology. 2007;189:4418-4424
  43. 43. Klausen M, Aaes-Jorgensen A, Molin S, Tolker-Nielsen T. Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms. Molecular Microbiology. 2003a;50:61-68
  44. 44. Klausen M, Heydorn A, Ragas P, Lambertsen L, Aaes-Jorgensen A, Molin S, et al. Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants. Molecular Microbiology. 2003b;48:1511-1524
  45. 45. Watnick PI, Kolter R. Steps in the development of a Vibrio cholerae El Tor biofilm. Molecular Microbiology. 1999;34:586-595
  46. 46. Schmidt J, Musken M, Becker T, Magnowska Z, Bertinetti D, Moller S, et al. The Pseudomonas aeruginosa chemotaxis methyltransferase CheR1 impacts on bacterial surface sampling. PLoS One. 2011;6:e18184
  47. 47. Hadjifrangiskou M, Kostakioti M, Chen SL, Henderson JP, Greene SE, Hultgren SJ. A central metabolic circuit controlled by QseC in pathogenic Escherichia coli. Molecular Microbiology. 2011;80:1516-1529
  48. 48. Dunne WM Jr. Bacterial adhesion: Seen any good biofilms lately? Clinical Microbiology Reviews. 2002;15:155-166
  49. 49. Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, et al. Induction and evasion of host defenses by type-1-piliated uropathogenic Escherichia coli. Science. 1998;282:1494-1497
  50. 50. Hung CS, Bouckaert J, Hung D, Pinkner J, Widberg C, DeFusco A, et al. Structural basis of tropism of Escherichia coli to the bladder during urinary tract infection. Molecular Microbiology. 2002;44:903-915
  51. 51. Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ. Type 1 pilus-Mediated bacterial invasion of bladder epithelial cells. The EMBO Journal. 2000;19:2803-2812
  52. 52. Nilsson LM, Yakovenko O, Tchesnokova V, Thomas WE, Schembri MA, Vogel V, et al. The cysteine bond in the Escherichia coli FimH adhesin is critical for adhesion under flow conditions. Molecular Microbiology. 2007;65:1158-1169
  53. 53. Garofalo CK, Hooton TM, Martin SM, Stamm WE, Palermo JJ, Gordon JI, et al. Escherichia coli from urine of female patients with urinary tract infections is competent for intracellular bacterial community formation. Infection and Immunity. 2007;75:52-60
  54. 54. Wright KJ, Seed PC, Hultgren SJ. Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili. Cellular Microbiology. 2007;9:2230-2241
  55. 55. Chen SL, Hung CS, Xu J, Reigstad CS, Magrini V, Sabo A, et al. Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: A comparative genomics approach. Proceedings of the National Academy of Sciences. 2006;103:5977-5982
  56. 56. Chen SL, Hung CS, Pinkner JS, Walker JN, Cusumano CK, Li Z, et al. Positive selection identifies an in vivo role for FimH during urinary tract infection in addition to mannose binding. Proceedings of the National Academy of Sciences. 2009;106:22439-22444
  57. 57. Hasman H, Chakraborty T, Klemm P. Antigen-43 mediated auto aggregation of Escherichia coli is blocked by fimbriation. Journal of Bacteriology. 1999;181:4834-4841
  58. 58. Uhlich GA, Cooke PH, Solomon EB. Analyses of the red-dry-rough phenotype of an Escherichia coli O157:H7 strain and its role in biofilm formation and resistance to antibacterial agents. Applied and Environmental Microbiology. 2006;72:2564-2572
  59. 59. Mohamed JA, Teng F, Nallapareddy SR, Murray BE. Pleiotrophic effects of 2 Enterococcus faecalis sagA-like genes, salA and salB, which encode proteins that are antigenic during human infection, on biofilm formation and binding to collagen type I and fibronectin. The Journal of Infectious Diseases. 2006;193:231-240
  60. 60. Toledo-Arana A, Valle J, Solano C, Arrizubieta MJ, Cucarella C, Lamata M, et al. The enterococcal surface protein, Esp, is involved in Enterococcus faecalis biofilm formation. Applied and Environmental Microbiology. 2001;67:4538-4545
  61. 61. Kemp KD, Singh KV, Nallapareddy SR, Murray BE. Relative contributions of Enterococcus faecalis OG1RF sortase-encoding genes, srtA and bps (srtC), to biofilm formation and a murine model of urinary tract infection. Infection and Immunity. 2007;75:5399-5404
  62. 62. Kai-Larsen Y, Luthje P, Chromek M, Peters V, Wang X, Holm A, et al. Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37. PLoS Pathogens. 2010;6:e1001010
  63. 63. Cegelski L, Pinkner JS, Hammer ND, Cusumano CK, Hung CS, Chorell E, et al. Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation. Nature Chemical Biology. 2009;5:913-919
  64. 64. Wang X, Preston JF 3rd, Romeo T. The pgaABCD locus of Escherichia coli promotes the synthesis of a polysaccharide adhesin required for biofilm formation. Journal of Bacteriology. 2004;186:2724-2734
  65. 65. Harmsen M, Yang L, Pamp SJ, Tolker-Nielsen T. An update on Pseudomonas aeruginosa biofilm formation, tolerance, and dispersal. FEMS Immunology and Medical Microbiology. 2010;59:253-268
  66. 66. Wittschier N, Lengsfeld C, Vorthems S, Stratmann U, Ernst JF, Verspohl EJ, et al. Large molecules as anti-adhesive compounds against pathogens. The Journal of Pharmacy and Pharmacology. 2007;59:777-786. [PubMed]
  67. 67. Starkey M, Hickman JH, Ma L, Zhang N, DeLong S, Hinz A, et al. Pseudomonas aeruginosa rugose small-colony variants have adaptations that likely promote persistence in the cystic fibrosis lung. Journal of Bacteriology. 2009;191:3492-3503
  68. 68. Yang L, Barken KB, Skindersoe ME, Christensen AB, Givskov M, Tolker-Nielsen T. Effects of iron on DNA release and biofilm development by Pseudomonas aeruginosa. Microbiology. 2007;153:1318-1328
  69. 69. Allesen-Holm M, Barken KB, Yang L, Klausen M, Webb JS, Kjelleberg S, et al. A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms. Molecular Microbiology. 2006;59:1114-1128
  70. 70. Barken KB, Pamp SJ, Yang L, Gjermansen M, Bertrand JJ, Klausen M, et al. Roles of type IV pili, flagellum-mediated motility and extracellular DNA in the formation of mature multicellular structures in Pseudomonas aeruginosa biofilms. Environmental Microbiology. 2008;10:2331-2343
  71. 71. Thomas VC, Thurlow LR, Boyle D, Hancock LE. Regulation of autolysis-dependent extracellular DNA release by Enterococcus faecalis extracellular proteases influences biofilm development. Journal of Bacteriology. 2008;190:5690-5698
  72. 72. Thomas VC, Hiromasa Y, Harms N, Thurlow L, Tomich J, Hancock LE. A fratricidal mechanism is responsible for eDNA release and contributes to biofilm development of Enterococcus faecalis. Molecular Microbiology. 2009;72:1022-1036
  73. 73. Guiton PS, Hung CS, Kline KA, Roth R, Kau AL, Hayes E, et al. Contribution of autolysin and Sortase A during Enterococcus faecalis DNA-dependent biofilm development. Infection and Immunity. 2009;77:3626-3638
  74. 74. Hong SH, Lee J, Wood TK. Engineering global regulator Hha of Escherichia coli to control biofilm dispersal. Microbial Biotechnology. 2010;3:717-728
  75. 75. Rowe MC, Withers HL, Swift S. Uropathogenic Escherichia coli forms biofilm aggregates under iron restriction that disperse upon the supply of iron. FEMS Microbiology Letters. 2010;307:102-109
  76. 76. Karatan E, Watnick P. Signals, regulatory networks, and materials that build and break bacterial biofilms. Microbiology and Molecular Biology Reviews. 2009;73:310-347
  77. 77. Kaplan JB. Biofilm dispersal: Mechanisms, clinical implications, and potential therapeutic uses. Journal of Dental Research. 2010;89:205-218
  78. 78. Wood TK, Hong SH, Ma Q. Engineering biofilm formation and dispersal. Trends in Biotechnology. 2010;29:87-94
  79. 79. Boyd A, Chakrabarty AM. Role of alginate lyase in cell detachment of Pseudomonas aeruginosa. Applied and Environmental Microbiology. 1994;60:2355-2359
  80. 80. Wang X, Dubey AK, Suzuki K, Baker CS, Babitzke P, Romeo T. CsrA post-transcriptionally represses pgaABCD, responsible for synthesis of a biofilm polysaccharide adhesin of Escherichia coli. Molecular Microbiology. 2005;56:1648-1663
  81. 81. Webb JS, Thompson LS, James S, Charlton T, Tolker-Nielsen T, Koch B, et al. Cell death in Pseudomonas aeruginosa biofilm development. Journal of Bacteriology. 2003;185:4585-4592
  82. 82. Lam H, Oh DC, Cava F, Takacs CN, Clardy J, de Pedro MA, et al. D-amino acids govern stationary phase cell wall remodeling in bacteria. Science. 2009;325:1552-1555
  83. 83. Kolodkin-Gal I, Romero D, Cao S, Clardy J, Kolter R, Losick R. D-amino acids trigger biofilm disassembly. Science. 2010;328:627-629
  84. 84. Kolodkin-Gal I, Cao S, Chai L, Bottcher T, Kolter R, Clardy J, et al. A self-produced trigger for biofilm disassembly that targets exopolysaccharide. Cell. 2012;149:684-692
  85. 85. Justice SS, Hung C, Theriot JA, Fletcher DA, Anderson GG, Footer MJ, et al. Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis. Proceedings of the National Academy of Sciences. 2004;101:1333-1338
  86. 86. Eto DS, Jones TA, Sundsbak JL, Mulvey MA. Integrin mediated host cell invasion by type 1-piliated uropathogenic Escherichia coli. PLoS Pathogens. 2007;3:e100
  87. 87. Bishop BL, Duncan MJ, Song J, Li G, Zaas D, Abraham SN. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nature Medicine. 2007;13:625-630
  88. 88. Schwartz DJ, Chen SL, Hultgren SJ, Seed PC. Population dynamics and niche distribution of uropathogenic Escherichia coli during acute and chronic urinary tract infection. Infection and Immunity. 2011;79:4250-4259
  89. 89. Anderson GG, Martin SM, Hultgren SJ. Host subversion by formation of intracellular bacterial communities in the urinary tract. Microbes and Infection. 2004;6:1094-1101
  90. 90. Rosen DA, Hooton TM, Stamm WE, Humphrey PA, Hultgren SJ. Detection of intracellular bacterial communities in human urinary tract infection. PLoS Medicine. 2007;4:e329
  91. 91. Reigstad CS, Hultgren SJ, Gordon JI. Functional genomic studies of uropathogenic Escherichia coli and host urothelial cells when intracellular bacterial communities are assembled. The Journal of Biological Chemistry. 2007;282:21259-21267
  92. 92. Henderson JP, Crowley JR, Pinkner JS, Walker JN, Tsukayama P, Stamm WE, et al. Quantitative metabolomics reveals an epigenetic blueprint for iron acquisition in uropathogenic Escherichia coli. PLoS Pathogens. 2009;5:e1000305
  93. 93. Hansen DS, Gottschau A, Kolmos HJ. Epidemiology of Klebsiella bacteremia: A case control study using Escherichia coli bacteremia as control. The Journal of Hospital Infection. 1998;38:119-132
  94. 94. Garcia-Medina R, Dunne WM, Singh PK, Brody SL. Pseudomonas aeruginosa acquires biofilm-like properties within airway epithelial cells. Infection and Immunity. 2005;73:8298-8305
  95. 95. Ubeda C, Taur Y, Jenq RR, Equinda MJ, Son T, Samstein M, et al. Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. The Journal of Clinical Investigation. 2010;120:4332-4341
  96. 96. Hoiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. International Journal of Antimicrobial Agents. 2010;35:322-332
  97. 97. Zimmerli W, Lew PD, Waldvogel FA. Pathogenesis of foreign body infection. Evidence for a local granulocyte defect. The Journal of Clinical Investigation. 1984;73(4):1191-1200
  98. 98. Donlan RM. Preventing biofilms of clinically relevant organisms using bacteriophage. Trends in Microbiology. 2009;17:66-72
  99. 99. Sutherland IW, Hughes KA, Skillman LC, Tait K. The interaction of phage and biofilms. FEMS Microbiology Letters. 2004;232:1-6
  100. 100. Burrowes B, Harper DR, Anderson J, McConville M, Enright MC. Bacteriophage therapy: Potential uses in the control of antibiotic-resistant pathogens. Expert Review of Anti-Infective Therapy. 2011;9:775-785
  101. 101. Yang D, Biragyn A, Kwak LW, Oppenheim JJ. Mammalian defensins in immunity: More than just microbicidal. Trends in Immunology. 2002;23:291-296
  102. 102. Pompilio A, Scocchi M, Pomponio S, Guida F, Di Primio A, Fiscarelli E, et al. Antibacterial and anti-biofilm effects of cathelicidin peptides against pathogens isolated from cystic fibrosis patients. Peptides. 2011;32:1807-1814
  103. 103. Kharidia R, Liang JF. The activity of a small lytic peptide PTP-7 on Staphylococcus aureus biofilms. Journal of Microbiology. 2011;49:663-668
  104. 104. Chen X, Schluesener HJ. Nanosilver: A nanoproduct in medical application. Toxicology Letters. 2008;176:1-12
  105. 105. Kim JS, Kuk E, Yu KN, Kim JH, Park SJ, Lee HJ, et al. Antimicrobial effects of silver nanoparticles. Nanomedicine. 2007;3:95-101
  106. 106. Feng QL, Wu J, Chen GQ , Cui FZ, Kim TN, Kim JO. A mechanistic study of the anti-bacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. Journal of Biomedical Materials Research. 2000;52:662-668
  107. 107. Secinti KD, Ozalp H, Attar A, Sargon MF. Nanoparticle silver ion coatings inhibit biofilm formation on titanium implants. Journal of Clinical Neuroscience. 2011;18:391-395
  108. 108. Rendueles O, Kaplan JB, Ghigo JM. Antibiofilm polysaccharides. Environmental Microbiology. 2012;15(2):334-346. DOI: 10.1111/j.14622920.2012.02810.x
  109. 109. Pihl M, Davies JR, Chavez de Paz LE, Svensater G. Differential effects of Pseudomonas aeruginosa on biofilm formation by different strains of Staphylococcus epidermidis. FEMS Immunology and Medical Microbiology. 2010;59:439-446
  110. 110. Kim Y, Oh S, Kim SH. Released exopolysaccharide (r-EPS) produced from probiotic bacteria reduce biofilm formation of enterohemorrhagic Escherichia coli O157:H7. Biochemical and Biophysical Research Communications. 2009;379:324-329. [PubMed]
  111. 111. Zinger-Yosovich KD, Gilboa-Garber N. Blocking of Pseudomonas aeruginosa and Ralstonia solanacearum lectins by plant and microbial branched polysaccharides used as food additives. Journal of Agricultural and Food Chemistry. 2009;57:6908-6913. [PubMed]
  112. 112. Wang X, Wang Q , Yang M, Xiao J, Liu Q , Wu H, et al. QseBC controls flagellar motility, fimbrial hemagglutination and intracellular virulence in fish pathogen Edwardsiella tarda. Fish & Shellfish Immunology. 2011;30:944-953
  113. 113. Prüß BM. Involvement of Two-Component Signaling on Bacterial Motility and Biofilm Development. Journal of Bacteriology. 2017;199(18):e00259-e00217
  114. 114. Raad II, Fang X, Keutgen XM, Jiang Y, Sherertz R, Hachem R. The role of chelators in preventing biofilm formation and catheter-related bloodstream infections. Current Opinion in Infectious Diseases. 2008;21:385-392
  115. 115. Shanks RM, Sargent JL, Martinez RM, Graber ML, O’Toole GA. Catheter lock solutions influence staphylococcal biofilm formation on abiotic surfaces. Nephrology, Dialysis, Transplantation. 2006;21:2247-2255
  116. 116. Bookstaver PB, Williamson JC, Tucker BK, Raad II, Sherertz RJ. Activity of novel antibiotic lock solutions in a model against isolates of catheter-related bloodstream infections. The Annals of Pharmacotherapy. 2009;43:210-219
  117. 117. Chatzinikolaou I, Zipf TF, Hanna H, Umphrey J, Roberts WM, Sherertz R, et al. Minocycline-ethylene-diaminetetraacetate lock solution for the prevention of implantable port infections in children with cancer. Clinical Infectious Diseases. 2003;36:116-119
  118. 118. Bleyer AJ, Mason L, Russell G, Raad II, Sherertz RJ. A randomized, controlled trial of a new vascular catheter flush solution (minocycline-EDTA) in temporary hemodialysis access. Infection Control and Hospital Epidemiology. 2005;26:520-524
  119. 119. Fleming D, Rumbaugh KP. Approaches to dispersing medical biofilm. Microorganisms. 2017;5:15. DOI: 10.3390/microorganisms5020015
  120. 120. Lu TK, Collins JJ. Dispersing biofilms with engineered enzymatic bacteriophage. Proceedings of the National Academy of Sciences. 2007;104:11197-11202

Written By

Mansab Ali Saleemi, Navindra Kumari Palanisamy and Eng Hwa Wong

Submitted: June 23rd, 2018 Reviewed: July 16th, 2018 Published: November 5th, 2018

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Continue reading from the same book

View All
Chapter 4 Origin and Control Strategies of Biofilms in the C...

By Laura E. Castrillón Rivera, Alejandro Palma Ramos,...

1761 downloads

Chapter 5 Antimicrobial Agents: Antibacterial Agents, Anti-b...

By Yaw Duah Boakye, Newman Osafo, Cynthia Amaning Dan...

2078 downloads

Chapter 6 The Methods for Detection of Biofilm and Screening...

By Sahra Kırmusaoğlu

9934 downloads