VINAI C. THOMAS, PhD
My laboratory studies metabolic adaptations of staphylococci in response to various biologically relevant stresses. We have recently demonstrated that acetic acid, a byproduct of glucose catabolism, induces a novel programmed cell death (PCD) pathway in staphylococci. Although our studies have shown that acetic acid mediates its effects through intracellular acidification, the role of the acetate anion itself is unclear and an area of active research. In addition, we are currently identifying the molecular components of the PCD pathway and how PCD impacts the bacterial population's fitness. These projects touch upon multiple aspects of bacterial redox metabolism and physiology. Another area of active research involves understanding the physiological significance of staphylococcal nitric oxide synthase. NO is usually toxic to bacterial respiration, and it is unclear why pathogens like Staphylococcus aureus and Staphylococcus epidermidis would carry an enzyme (NOS) that makes NO. We have recently shown that endogenous NO produced by staphylococci is rapidly oxidized to nitrite and the latter species is the physiologically relevant effector of NOS function. We have determined that nitrite stimulates staphylococcal aerobic respiration and growth. How nitrite accomplishes this task is unknown and a topic that is currently being pursued in my laboratory.
Mazharul Islam M, Thomas VC*, Van Beek M, Ahn JS, Alqarzaee AA, Zhou C, Fey PD, Bayles KW, Saha R. An integrated computational and experimental study to investigate Staphylococcus aureus metabolism. NPJ Syst Biol Appl. 2020 Jan 30;6(1):3. doi: 10.1038/s41540-019-0122-3. PMID: 32001720; PMCID: PMC6992624. * Co-corresponding author
Hutfless EH, Chaudhari SS, Thomas VC. Emerging roles of nitric oxide synthase in bacterial physiology. Adv Microb Physiol. 2018;72:147-191. doi: 10.1016/bs.ampbs.2018.01.006. Epub 2018 Feb 26. PMID: 29778214.
Chaudhari SS, Kim M, Lei S, Razvi F, Alqarzaee AA, Hutfless EH, Powers R, Zimmerman MC, Fey PD, Thomas VC. Nitrite derived from endogenous bacterial nitric oxide synthase activity promotes aerobic respiration. mBio. 2017 Aug 1;8(4):e00887-17. doi: 10.1128/mBio.00887-17. PMID: 28765220; PMCID: PMC5539425.
Chaudhari SS, Thomas VC, Sadykov MR, Bose JL, Ahn DJ, Zimmerman MC, Bayles KW. The LysR-type transcriptional regulator, CidR, regulates stationary phase cell death in Staphylococcus aureus. Mol Microbiol. 2016 Sep;101(6):942-53. doi: 10.1111/mmi.13433. Epub 2016 Jul 4. PMID: 27253847; PMCID: PMC5014633.
Thomas VC, Sadykov MR, Chaudhari SS, Jones J, Endres JL, Widhelm TJ, Ahn JS, Jawa RS, Zimmerman MC, Bayles KW. A central role for carbon-overflow pathways in the modulation of bacterial cell death. PLoS Pathog. 2014 Jun 19;10(6):e1004205. doi: 10.1371/journal.ppat.1004205. PMID: 24945831; PMCID: PMC4063974.
Thomas VC, Kinkead LC, Janssen A, Schaeffer CR, Woods KM, Lindgren JK, Peaster JM, Chaudhari SS, Sadykov M, Jones J, AbdelGhani SM, Zimmerman MC, Bayles KW, Somerville GA, Fey PD. A dysfunctional tricarboxylic acid cycle enhances fitness of Staphylococcus epidermidis during β-lactam stress. mBio. 2013 Aug 20;4(4):e00437-13. doi: 10.1128/mBio.00437-13. Erratum in: MBio. 2014;5(3):e01307-14. Chittezham Thomas, Vinai [corrected to Thomas, Vinai C]. PMID: 23963176; PMCID: PMC3747581.