Accumulation of Succinyl Coenzyme A Perturbs the Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA) Succinylome and Is Associated with Increased Susceptibility to Beta-Lactam Antibiotics
Christopher Campbell, Claire Fingleton, Merve S. Zeden, Emilio Cendejas‐Bueno, Laura A. Gallagher, Dhananjay Shinde, Jongsam Ahn, Heather Olson, Thomas Fillmore, Joshua Adkins, Fareha Razvi, Kenneth W. Bayles, Paul D. Fey, Vinai C. Thomas, Felipe Cava, Gérémy Clair, James P. O’Gara
Abstract
, increased susceptibility to β-lactam antibiotics and was accompanied by significant accumulation of succinyl-CoA, which in turn perturbed lysine succinylation in the proteome. Although cell wall structure and cross-linking were unchanged, significantly increased succinylation of the major autolysin Atl, which was the most succinylated protein in the proteome, was accompanied by near complete repression of autolytic activity. These findings link central metabolism and levels of succinyl-CoA to the regulation of β-lactam antibiotic resistance in MRSA through succinylome-mediated control of two interlinked cell wall phenotypes. Drug-mediated interference of the SucCD-controlled succinylome may help overcome β-lactam resistance.