Abstract

Staphylococcus aureus is a highly successful pathogen due to its wide range of antibiotic and immune resistance mechanisms. One unique and concerning resistance factor involves S. aureus resistance to the antimicrobial radical nitric oxide (NO·). NO· is a membrane permeable gas produced by activated phagocytes to function as an antimicrobial agent against pathogens. NO· is usually an effective defense against bacteria; however, S. aureus is unique in that it is still able to replicate under nitrosative stress. The capability to persist under high levels of NO· is complex and hinges on the use of various genes and metabolic enzymes. FtsH is an ATP-dependent, zinc-binding metalloprotease located in the cell membrane of S. aureus and is critical for survival under environmental stressors. FtsH, as well as other proteolysis enzymes, play important roles in the elimination of misfolded and non- functional proteins. Although it has been implicated in NO· resistance with the use of deep sequencing of transposon junctions, its specific role during NO· stress is unknown. FtsH modulates levels of proteins potentially involved in both heme synthesis and respiration such as cydA, cyoE, and hemeA. NO· is capable of damaging heme and respiratory enzymes by reacting with iron, which temporarily inhibits respiration in S. aureus, so we hypothesized that ftsH plays a role in regulating damage to the electron transport chain. Here, we utilize a modified allelic exchange method to create an ftsH deletion mutant. Future studies will define the role of ftsH during NO·, specifically how it impacts recovery of respiration

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