Staphylococcus aureus persisters exhibit increased tolerance to oxygen and nitrogen species 3097

Abstract Description Staphylococcus aureus is an opportunistic pathogen responsible for a number of infections, many of which are biofilm-mediated and relapsing. Recently, we demonstrated S. aureus biofilms are primarily composed of persister cells. Additionally, we found interruption of the tricarboxylic acid cycle, specifically a fumC knockout (fumC::NΣ), increased persister cell formation and led to an increased tolerance to antimicrobial peptides. Given the fumC knockout exhibited increased tolerance to a component of innate immunity, we hypothesized persisters would exhibit increased survival to other components of the innate immune system. When examining persister survival in a macrophage cell line (RAW 264.7), fumC::NΣ exhibited a 1-log increase in survival compared to wild type S. aureus. Given this, persister survival to antimicrobial components found within macrophages was investigated further. Paraquat and sodium nitrite (NaNO2) were used to induce reactive oxygen and nitrogen species (RONS). Wild type S. aureus and fumC::NΣ were challenged with sublethal and lethal concentrations of NaNO2 and paraquat. Following sublethal challenge, fumC::NΣ exhibited an increased growth rate to RONS compared to wild type S. aureus. Similarly, following lethal challenge with NaNO2 (96mM) and paraquat (10mM), fumC::NΣ exhibited a 1 log increase in survival compared to the wild type. These data suggest persisters have a survival advantage to compounds within macrophages. Funding Sources Supported by the National Institute of General Medical Science of the National Institutes of Health (NIH) under award number GM103427. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)