aureus and C. albicans[23]. Enhancement of biofilms, increased catheter infection and dissemination of S. epidermidis in mixed species biofilms in vivo may partly explain clinical therapeutic failures and contribute to increased mortality and morbidity in polymicrobial infections. We performed microarrays to delineate changes in staphylococcal gene expression that lead to increased catheter infection and dissemination in mixed species biofilms with C. albicans. We noted that the lrg operon comprising lrgA and lrgB was highly down regulated (36 fold and 27 fold change respectively) in mixed species biofilms. Lrg selleck screening library operon along

with the cidR operon represents the molecular elements of programmed cell death or apoptosis in Staphylococcus aureus[25–27]. The lrg operon is a repressor of murein BIBW2992 purchase hydrolase activity that hydrolyzes components of the cell wall, involved in autolysis. Lrg protein has also been shown to affect antibiotic tolerance, biofilm formation (by release of eDNA which is a structural component of the biofilm) and acetoin production in S. aureus[25, 26, 28, 29]. Lrg operon is regulated by the LytSR two component regulatory

system in S. aureus and transcriptional regulators agr and sar that regulate virulence also influence the lrg operon [28, 29]. Down regulation of the lrg operon (autolysis repressors) in mixed species biofilms is associated with enhanced release of eDNA possibly by autolysis [25, 30]. Extracellular DNA plays a significant role in biofilm aggregation [18, 19] and it is conceivable that increased eDNA enhances aggregation of mixed species biofilms of S. epidermidis and C. albicans. Most bacteria have cardiolipin synthases that convert

bacterial membrane phosphatidyl glycerol to cardiolipin, during the transition from logarithmic phase to the stationary phase and may help survival during prolonged Aprepitant high salt stress conditions [31]. S. aureus and S. epidermidis have 2 ORFs cls1 and cls2[32] and we found cardiolipin synthetase (cls2) was significantly down regulated. Other down regulated genes included those associated with carbohydrate, amino acid and nucleotide metabolism, transporters and other proteins. Biofilm as a whole may be metabolically less active compared to actively dividing planktonic organisms and that may explain the down regulation of metabolic processes and overall more down regulated genes (6%) than upregulated genes (2.7%) [33]. Genes upregulated in mixed species biofilms include transcriptional regulators (sarR and hrcA the heat inducible transcriptional repressor), genes associated with nucleic acid metabolism, some transporters and other proteins. sarR is known inhibitor of sarA, a transcriptional regulator that represses extracellular proteases and that may influence virulence determinants in S. aureus[34–36] but its role in S. epidermidis is not known.