subtilis mutants defective in the cardiolipin synthase gene [30]. MIC values of vancomycin or cycloserine inhibiting late and early stages of peptidogylcan synthesis were not affected in cpoA mutants, an indication that the cell wall biochemistry is not affected. Interestingly, cpoA mutants were ten-fold more susceptible to bacitracin, which targets the lipid molecule bactoprenol. The cpoA mutants expressed an altered transcription profile compared to that of the R6 strain, mainly by genes encoding

membrane proteins such as PTS systems or ABC transporters Trametinib mouse that represent minor components of the bacterial cell. On the other hand, we could not detect significant changes of the protein profile of cytoplasmic or PSI-7977 concentration membrane proteins on SDS-polyacrylamide gels, i.e. no major protein components were affected in terms of quantity (not shown). It is conceivable that the transcriptional changes might be an indirect effect of the altered membrane composition. We recently reported that a higher susceptibility to bacitracin was also noted in S. pneumoniae containing a mutated ABC transporter [31]. It is possible that the altered lipid composition of the cpoA mutants indirectly affects the ABC transporter function and thus bacitracin MIC. Glycolipids as anchor molecules in Gram-positive bacteria Glycolipids represent the membrane anchor of important membrane-bound cell wall polymers in Gram-positive bacteria. They function as the lipid anchor for LTA

and also for another class of membrane-associated cell wall glycopolymers, lipoglycans, which seem to replace LTA in the high GC division of Gram-positive bacteria [32, 33]. Listeria contain the same glycolipids as S. pneumoniae, whereas GlcDAG and GlcGlcDAG represent the major glycolipids in Bacillus, Staphylococcus and Enterococcus. However, these species differ in their biosynthetic enzymes. In Sapanisertib manufacturer Bacillus and Staphylococcus, both glycolipids are synthesized by one single GT YpfP [34–36], whereas two putative GTs are involved in glycolipid biosynthesis in Listeria, Streptococcus and Enterococcus[9, 10, 37, 38]. In this context it is remarkable that the structure

of the cpoA operon which includes obg and several putative small peptide encoding genes is only maintained within Streptococcus spp., and that other Gram-positive bacteria contain cpoA (plus spr0982 in case of Listeria and Enterococcus) and obg homologues at Carbachol distinct positions in the genome. The reason for this is not clear. Several studies revealed that Obg proteins play a role in many important processes, including DNA replication, chromosome segregation, and regulation of stress responses, but their actual function remains unknown [for review, see [19]]. Most of the species mentioned above contain a polyglycerophosphate LTA backbone which is anchored to the di-glycosyl-DAG lipid. Thus, interference of the biosynthesis of this glycolipid severely affects LTA and accordingly cell wall integrity as was shown for mutants in the S.