It has been demonstrated in a wide variety of bacteria that death and lysis of a subpopulation of cells can facilitate biofilm formation due to the release of DNA into the extracellular environment (eDNA) [17–22]. Likewise, cell death and lysis have been implicated in dispersal of cells from a mature biofilm [23–25]. In Staphylococcus

aureus, the Cid/Lrg system has been shown to be involved in the regulation of cell death, autolysis, and biofilm formation [17, 21, 26–28]. Characterization of S. aureus cid and lrg mutants has revealed that these operons have opposing effects on cell death and murein hydrolase activity [27, 29]. These observations, combined with the fact that LrgA and CidA share structural features with JQ-EZ-05 nmr the bacteriophage lambda family of holin proteins [29], have led to the hypothesis that CidA and LrgA control cell death and lysis in a manner analogous to effector and inhibitor holins, respectively [26, 30]. Bacteriophage holins are small membrane proteins that oligomerize Luminespib in vivo in the cell membrane, acting as “molecular clocks” that regulate the timing and lysis

of the host cell during lytic infection [31]. For example, the lambda S holin regulates cell death and lysis by the formation of large lipid-excluding “rafts” that promote cytosolic leakage as well as access of the phage-encoded endolysin (murein hydrolase) to the cell wall [32–34]. S. aureus CidA and LrgA have recently been shown to oligomerize into high-molecular-mass complexes in a cysteine disulfide Combretastatin A4 molecular weight bond-dependent manner, a biochemical feature also shared with holin proteins

[35]. Although the molecular details of how Cid and Lrg function to control cell death and lysis have not yet been completely elucidated, the fact that cid and lrg homologues have been identified in a wide variety of bacterial and archeal genomes supports a fundamental and conserved role for this system in cell physiology C59 mw [30, 36]. In previous work it was determined that expression of potential cidAB and lrgAB homologues in S. mutans is highly responsive to carbohydrate availability [12, 37] and oxygenation [11]. Given the potential importance of these genes to biofilm development in S. mutans, we previously characterized a panel of S. mutans cid and lrg isogenic mutants and found that a subset of these genes did indeed influence biofilm formation, production of glucosyltransferases (enzymes that synthesize extracellular glucan polymers that contribute to biofilm adhesion), and oxidative stress tolerance [37]. In this study it was also found that, as demonstrated previously in S. aureus[38, 39], the S. mutans LytST two-component system was required for activation of lrgAB expression, but not cidAB expression [37].