The suf iron-sulfur cluster biosynthetic system is essential for staphylococcus aureus viability and decreased suf function results in global metbolic defects and decreased survival in human neutrophils
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Roberts, Christina. The suf iron-sulfur cluster biosynthetic system is essential for staphylococcus aureus viability and decreased suf function results in global metbolic defects and decreased survival in human neutrophils. Retrieved from https://doi.org/doi:10.7282/T3W37ZMH
TitleThe suf iron-sulfur cluster biosynthetic system is essential for staphylococcus aureus viability and decreased suf function results in global metbolic defects and decreased survival in human neutrophils
DescriptionStaphylococcus aureus remains a causative agent for morbidity and mortality worldwide. This is in part a result of antimicrobial resistance highlighting the need to uncover novel antibiotic targets and discover new therapeutic agents. In this study we explored the possibility of iron-sulfur (FeS) cluster synthesis as a viable antimicrobial target. RNA interference studies verified that Suf-dependent FeS cluster synthesis was essential in S. aureus. Two S. aureus strains were characterized that contained transposon insertions between suf genes (suf*) resulting in decreased transcription of genes downstream of the insertions. We found that the sufCDSUB genes were cotranscribed and suf transcription was positively influenced by general stress sigma factor B. The suf* strains had decreased activities of FeS cluster-requiring enzymes and decreased growth in media lacking metabolites that require FeS proteins for synthesis. Decreased FeS cluster synthesis also resulted in sensitivity to reactive oxygen and reactive nitrogen species. Decreased Suf function resulted in increased DNA damage and defective DNA repair. It also resulted in decreased flux though the TCA cycle and decreased cellular respiration. The suf* mutants had perturbed intracellular non-chelated Fe pools. Defective FeS cluster synthesis did not alter exoprotein production or biofilm formation, but it did result in decreased survival upon challenge with human polymorphonuclear leukocytes. The results presented suggest that FeS cluster synthesis is a viable target for antimicrobial development. The strains and DNA constructs described provide a genetic toolbox for further examination of FeS cluster synthesis in S. aureus.