Delineating the Role of the Operon in Staphylococcal Overflow Metabolism.

is an important human pathogen that can infect almost every organ system, resulting in a high incidence of morbidity and mortality. The operon is an important regulator of several staphylococcal phenotypes, including biofilm development, cell wall crosslinking, antibiotic resistance, oxidative stress, and acute and chronic implant-associated osteomyelitis. Our previous study showed that, by modulating murein hydrolase activity, the operon negatively regulates the proteases that govern cell death. Here, we report further elucidation of the mechanism of cell death, which is regulated by the operon at the molecular level in the USA300 LAC strain. We showed that deletion of enhances weak-acid-dependent cell death, because, in the biofilm microenvironment, this mutant strain consumes glucose and produces acetate and acetoin at higher rates than wild-type USA300 LAC strain. We proposed the increased intracellular acidification leads to increased cell death. MsaB, a dual-function transcription factor and RNA chaperone, is a negative regulator of the regulon, which has been shown to play an important role in overflow metabolism and programmed cell death during biofilm development in . We found that MsaB binds directly to the promoter, which represses expression of the regulon and prevents transcription of the and operons. In addition, we observed that pyruvate induced expression of the operon (MsaB). The results reported here have enabled us to decipher the role of the operon in staphylococcal metabolic adaption during biofilm development.