Biofilm
Abstracts & Commentary
Joseph F. John, Jr., MD , Chief, Medical Subspecialty Services, Ralph H. Johnson Veterans Administration Medical Center; Professor of Medicine, Medical University of South Carolina, Charleston, SC, is Co-Editor for Infectious Disease Alert
Synopsis: Growth in biofilm is associated with dramatic changes in gene expression by S. epidermidis.
Sources: Yao Y, et al. Genomewide Analysis of Gene Expression in Staphylococcus epidermidis Biofilms: Insights into the Pathophysiology of S. epidermidis Biofilms and the Role of Phenol-Soluble Modulins in Formation of Biofilms. J Infect Dis. 2005;191:289-298; Kocianova S, et al. Key Role of Poly-Gamma- DL-Glutamic Acid in Immune Evasion and Virulence of Staphylococcus epidermidis. J Clin Invest. 2005;115:688-694.
Staphylococcus epidermidis continues to be a troublesome pathogen, mainly due to its ability to form biofilms that protect this species and allow it to express unique features that guarantee its survival. The main molecules involved in biofilm formation are under intense study. In the present study, the group at the Rocky Mountain NIH laboratory used a microarray representing all the known S. epidermidis genes in a strain known as 1457 to determine the gene usage in planktonic versus biofilm stages. Two types of non-biofilm experiments were done, and the expression values averaged. The first involved planktonic bacteria grown in flasks. The second used non-adherent bacteria recovered from the statically grown cultures in polytstyrene dishes.
Analysis of gene usage involves a complex software analysis. In all the open reading frames (ORFs) of 2633 S. epidermidis genes were annotated. RNA was extracted from planktonic and biofilm bacteria, reverse transcribed into cDNA and displayed on a microarray.
Microarray experiments yield an immense amount of data. The results of this large undertaking using just one strain of biofilm-forming S. epidermidis produced some expected and unexpected results. Planktonic cells generally behave in an aggressive, proinflamatory, metabolically active manner and use aerobic respiration. Biofilm cells behave the opposite: nonagressive, avoiding immune responses, and using a low metabolic quotient.
So as might be expected in these staphylococcal biofilms, down-regulated genes include those of global regulatory systems, adhesion factors, and aerobic production of energy. Many other proteins, some hypothetical, are also downregulated.
Of note from this study, is a family of proteins called phenol-soluble modulins (PSMs) that are upregulated in planktonic bacteria and downregulated in biofiilms. Yao and colleagues also measured PSMs in planktonic versus biofilm bacteria and found the PSMs many times higher in the former.
Upregulated genes include those of osmoprotection, one global regulator, fermentation, chaperone or stress response, and several others. Some of the more interesting ones were Drp35, an antibiotic resistant determinant, a zinc resistance protein CzrB, and the CapC, one of the proteins of the poly-gamma glutamate biosynthesis complex. These data suggest that S. epidermidis sees the biofilm as a hostile environment and mobilizes genes that allow it to resist that hostile environment.
In a related article also by Yao et al, the organism is the focus. There is an anionic, extracellular polymer known to be secreted by strains of Bacillus known as poly- -DL-glutamic acid (PGA). In this accompanying, exhaustive work, PGA was shown to shelter S. epidermidis from high salt concentration. There are a series of genes known as the cap genes, and the sequence of capBcapCcapAcapD that is present in Bacillus anthrasis has the same sequence in S. epidermidis. Yao et al showed that PGA can be seen by immunoscanning electron microscopy to stick to the surface of the bacteria and helps the bacterium resist high salt concentrations, up to 2 M NaCl.
They showed further that the cap products helped the staphylococci stick to subcutaneous catheters and that PGA assists in resisting innate immune attack by bacterial peptides. The capB and capD genes were present in a wide variety of coagulase-negative staphylococcal strains, including S. simulans, S. caprae, S. warneri, S. capitis, S. haemolyticus, and S. hominis.
Comment by Joseph F. John, Jr., MD
The work by Yao et al, and that of other groups around the world, is leading to a holistic view of the bacterial biofilm. Biofilms are important medically, since they form an apparently protective environment for pathogenic bacteria.
That biofilms protect bacteria within the biofilm is too simplistic a view that does not take into account the response of the bacteria to the biofilm environment. The current papers demonstrates that biofilms develop through a multistep process in which the bacterium in question alters its viability traits to survive the biofiolm enviornment. Aggressive metabolically active genes are turnes off, immune evasion, and fermentation genes are turned on. If this sounds like the production of a spore in spore-forming bacteria, the ring is true. Gene products, like PSMs, may even inhibit biofilm formation and, thus, must be downregulated, either directly or through global regulators like agr.
At the same time, the paper by Kocianova and colleagues. shows that the coagulase-negative staphylococci have some newly found weapons, namely PGA. It sounds like PGA may be so central to infections with these particularly sticky bacteria that pharmacologic or immune tools to block PGA or the genes that encode it should be developed soon. S. epidermidis continues to be the no. 1 isolate from blood in hospitalized patients. We are starting to understand much better the molecular pathogenesis of these pesky commensals as evidenced by these 2 sophisticated papers.
Staphylococcus epidermidis continues to be a troublesome pathogen, mainly due to its ability to form biofilms that protect this species and allow it to express unique features that guarantee its survival. The main molecules involved in biofilm formation are under intense study.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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