Crucial Role for Lipoteichoic Acid Assembly in the Metabolic Versatility and Antibiotic Resistance of Staphylococcus aureus

• DOI: 10.1128/iai.00550-22
• Publication Date: 2023-06-23T05:24:15Z
• Authors: Troy A. Burtchett; John C. Shook; Laura E. Hesse; Philip C. Delekta; Robert S. Brzozowski; Alhakam Nouri; Alexa J. Calas; Catherine M. Span...; Prahathees J. Eswara; Neal D. Hammer
• Keywords: Lipoteichoic acid

Staphylococcus aureus is a public health threat due to the prevalence of antibiotic resistance and capacity this organism infect numerous organs in vertebrates. To generate energy needed proliferate within tissues, S. transitions between aerobic respiration fermentation. Fermentation results distinct colony morphology called small-colony variant (SCV) decreased membrane potential ATP production. These traits promote increased aminoglycoside antibiotics. Consequently, SCVs are associated with persistent infections. We hypothesize that dedicated physiological pathways support fermentative growth represent targets for treatment resistant Lipoteichoic acid (LTA) an essential component Gram-positive cell envelope functions maintain ion homeostasis, resist osmotic stress, regulate autolytic activity. Previous studies revealed perturbation LTA reduces viability metabolically restricted aureus, but mechanism by which supports metabolic versatility unknown. Though essential, enzyme synthesizes modified lipid anchor, YpfP, dispensable. However, ypfP mutants produce altered LTA, leading elongation polymer association. demonstrate significantly reduced upon environmental genetic induction This anaerobic defect correlates restored cation supplementation. Additionally, suppressor exhibiting harbor compensatory mutations biosynthetic pathway restore potential. Overall, these maintains during proliferation promotes versatility.