I felt of discussing something entirely new and challenging and came out with the biofilms. This is very extraordinary understanding and currently many researchers are working on understanding biofilm production by certain species and particularly in Staphylococcus spp, which is known to cause nosocomial infections (hospital acquired). Although the topic may be not new to you but better understanding of how they form and why they form may lead to some new knowledge uptake. You can also add comments below this article to make it more understanding to the readers.
So what are biofilms? – Biofilms are adherent communities of bacteria containing within a complex matrix. The adherents are known to be embedded inside the extracellular polymeric substances (EPS) which is commonly known as EPS matrix. Biofilms are found on both living as well as non-living surfaces. Biofilm EPS or slime generally composed of extracellular DNA, polysaccharides and proteins. There are varied reasons why biofilms are produced by certain bacteria. It is known that Staphylococcal biofilms can escape immune recognition, because of their chronic and indolent nature. Biofilms serve to be very useful for Staphylococcus in many ways including development of antibiotic resistance, and as mentioned to escape immune reponse.
Development of biofilms starts with the initial weak reversible adhesion on to a surface with van der Waals forces. Some motile bacteria anchor themselves more permanently using cell adhesion structures, pili. Secondly, hydrophobicity plays role to determine the bacteria able to form biofilms, since increased hydrophobicity have reduced repulsion between extracellular matrix and the bacteria. Recently, quorum sensing also sound to play major role, where cells communicate among themselves, transmitting signals (using products like AHL) during colonization. Once the colonization has started, biofim grows with the cell division. Dispersion is the final stage of the development of biofilm where the biofilm changes only its shape and size.
Quorum sensing – An accessory gene regulator(agr) is thought to play an important role in quorum sensing system in causing serious biofilm associated diseases by Staphylococcus aureus. In an experiment by Yarwood (2004) and his colleagues, from University of Lowa examined the agr dependent transcription in biofilms. The observation of their research draws much significant conclusion. While disruption of agr expression, there is no significant influence in biofilm formation, but where this the presence of agr , there is an enhanced biofilm formation. Under those conditions where agr expression enhanced biofilm formation, biofilms of an agr signaling mutant were particularly sensitive to rifampin but not to oxacillin. Time lapse confocal scanning laser microscopy showed that, similar to the expression of an agr-independent fluorescent reporter, biofilm expression of an agr-dependent reporter was in patches within cell clusters and oscillated with time. In some cases, loss of fluorescence appeared to coincide with detachment of cells from the biofilm. Their studies indicates that biofilm development and behavior depends on environmental conditions. It also gives suggestion that detachment of cells expressing agr from biofilms may have important clinical implications. In 2006, Kong et al., highlights that along with agr, the post translationally modified peptide has an autoinducing signal towards quorum sensing. This second quorum sensing system, called luxS is found in variety of gram positive and gram negative bacteria. Both agr and luxS has different role, agr enhances biofilm detachment by up-regulation of the expression of detergent-like peptides, whereas luxS reduces cell-to-cell adhesion by down-regulating expression of biofilm exopolysaccharide.
Targeting quorum sensing has been now a potential target. While promising reports exist about quorum-sensing blockers in gram-negative bacteria, the use of the Staphylococcal quorum-sensing system as a drug target is now seen in an increasingly critical way. Inhibition of quorum-sensing in Staphylococcus has been shown to enhance biofilm formation. Furthermore, down-regulation or mutation of the Staphylococcus quorum-sensing system increases bacterial persistence in device-related infection, suggesting that interference with quorum-sensing would enhance rather than suppress this important type of Staphylococcal disease. The chemical nature and biological function of another proposed Staphylococcal quorum-sensing inhibitor, named “RIP”, are insufficiently characterized. Targeting quorum-sensing systems might in principle constitute a reasonable way to find novel antibacterial drugs.
ica Operon – The ability to form a biofilm affords at least two properties: the adherence of cells to a surface and accumulation to form multilayered cell clusters. A trademark is the production of the slime substance Polysaccharide Intercellular Adhesin (PIA), a polysaccharide composed of beta-1,6-linked N-acetylglucosamines with partly deacetylated residues, in which the cells are embedded and protected against the host’s immune defence and antibiotic treatment. Mutations in the corresponding biosynthesis genes (ica operon) lead to a pleiotropic phenotype; the cells are biofilm and haemagglutination negative, less virulent and less adhesive on hydrophilic surfaces. ica expression is modulated by various environmental conditions, appears to be controlled by SigB and can be turned on and off by insertion sequence (IS) elements. A number of biofilm-negative mutants have been isolated in which polysaccharide intercellular adhesin (PIA) production appears to be unaffected.
Other factors- Along with quorum sensing and ica operon, there are other proteins have been identified that are also involved in biofilm formation, such as the accumulation-associated protein (AAP), the clumping factor A (ClfA), the staphylococcal surface protein (SSP1) and the biofilm-associated protein (Bap).
Multidrug tolerance or antibiotic tolerance is the ability of the disease causing microbe to resist killing by antibiotics. This multidrug tolerance in biofilms is caused by a small subpopulation of microbial cells called persister cells. Persisters are not mutants but rather dormant cells that can survive the antimicrobial treatments that kill majority of their genetically identical siblings. Persisters enter into a slow growing physiological state which makes them insensitive to the action of antimicrobial drungs.
While concluding this article, I must say that this article is based on totally on Staphylococcus sp. and not highlighting any cure mechanisms against biofilms. I just have highlighted the major artifacts about biofim formation by Staphs. Please do comment and add some of your ideas over biofilms.
- Jeremy M. Yarwood, Dauglas J. Bartels, Esther M. Volper, E. Peter Greenberg. 2004.Quorum sensing in Staphylococcus aureus biofilms. Journal of bacteriology. 186(6): 1838-1850.
- Kong KF, Vuong C, Otto M. 2006. Staphylococcus quorum sensing in biofilm formation and infection. International Journal of Medical Microbiology. 296: 133-139.
- Otto M. 2004. Quorum-sensing control in Staphylococci — a target for antimicrobial drug therapy? – Review Article. FEMS Microbiology letters. 241(2): 135-141.
- Götz F. 2002. Staphylococcus and Biofilms. Molecular Mirobiology. 43(6): 1367-1378.