Biofilm In order to evaluate the validity of the hypothesis "catabolite control of S. epidermidis biofilm formation is indirectly regulated by CcpA-dependent of the TCA cycle," a laboratory study was performed and then documented in the article "CcpA coordinates central metabolism and biofilm formation in Staphylococcus epidermidis." Through their research, the authors of the article ultimately determined that CcpA is in fact a positive effecter of biofilm formation of S. epidermidis, along with icaADBC transcription and a repressor of TCA cycle activity.

The general profile of S. epidermidis shows that it is a pathogen that is opportunistic in nature, therefore primarily infecting patients who are immunocompromised. It is often a cause of infections for patients who receive implanted biomedical devices. This pathogen makes itself particularly difficult to treat in these situations due to the formation of a biofilm, which encapsulates the bacteria in an exopolysaccharide matrix. It is therefore valuable to discover a way in which to inhibit the formation of these biofilms in order to have a strong defense against the domination of this pathogen within a patient (Sadykov 2011).

It is a known that the formation of these biofilms, as well as the synthesis of the exopolysaccharides synthesis, is significantly influenced by the availability of nutrients and the environmental conditions. Of particular note pertaining to this study, the formation of the biofilm is enhanced while growing in media that contains glucose. What this fact would suggest is a carbon catabolite-responsive regulator activates the genes that are essential to the formation of biofilm, and/or it represses the genes that inhibit the formation of the biofilm (Sadykov 2011).

The authors of this article used many methods to conduct their examinations of the role of the CcpA in the ability of the pathogen to create a biofilm. This included constructing a S. epidermidis mutant, which contained an inactive CcpA. They then observed the effects that it had upon growth, biofilm formation, and virulence. Based on the data, the...

These findings are supported by another similar study, which point out that inactivation of the TCA cycle inhibits the bacterial growth. In both studies the mutant, which had been altered to depress or inactivate the TCA cycle, caused there to be noticeably less growth than with the wild type strain. The effect on the TCA cycle (and subsequent metabolic activity) was significant enough to alter growth patterns (Sandykov 2008). Vuong (2005) found that when they cultured S. epidermidis with a low concentration of fluorocitrate (a TCA cycle inhibitor), PIA production was significantly increased yet there was no effect on glucose catabolism, growth rate or growth yields. Their speculation based on this data was that one way in which staphylococci perceives changes in its external environment is through any alterations in TCA cycle activity. These alterations produce changes of biosynthetic intermediates in the intracellular level, ATP, or the status of redox of the cell. The result of these changes in the bacteria's metabolic status is attenuation or augmentation of PIA production. Results from the Fluckiger (2005) study agree upon PIA being an important virulence factor for S. epidermidis. However, what seems to be a point of contention is exactly which components are the ones with the most effect on the metabolic process. For example, Sadykov (2008) concludes that it is the CcpA (catabolite control protein A) which coordinates the central metabolism. Seidl (2008) concluded from their data that deleting ccpA (which is coding for the CcpA and regulates gene expression based on the carbon source) completely incapacitates biofilm formation under static and flow conditions. However, it still allowed for primary attachment to polystyrene surfaces. Still, this shows the crucial role that CcpA plays in whether or not there is biofilm formation. With CcpA as the regulator of transcriptions of genes involved in PIA synthesis and its ability to affect TCA cycle activity, it seems to be the key component that needs to…