Specialized phosphate transport is essential for Staphylococcus aureus nitric oxide resistance

Staphylococcus aureus is a major human pathogen capable of causing a variety of diseases ranging from skin and soft tissue infections to systemic presentations such as sepsis, endocarditis, and osteomyelitis. For S. aureus to persist as a pathogen in these environments, it must be able to resist the host immune response, including the production of reactive oxygen and nitrogen species (e.g., nitric oxide, NO). Extensive work from our lab has shown that S. aureus is highly resistant to NO, especially in the presence of glucose. RNA-seq performed on S. aureus exposed to NO in the presence and absence of glucose showed a new system important for NO resistance-phosphate transport. The phosphate transport systems pstSCAB and nptA are both upregulated upon NO-exposure, particularly in the presence of glucose. Both are key for phosphate transport at an alkaline pH, which the cytosol of S. aureus becomes under NO stress. Accordingly, the Delta pstS Delta nptA mutant is attenuated under NO stress in vitro as well as in macrophage and murine infection models. This work defines a new role in infection for two phosphate transporters in S. aureus and provides insight into the complex system that is NO resistance in S. aureus.

Automated summary

Staphylococcus aureus is highly resistant to nitric oxide (NO), especially in the presence of glucose. A new system of phosphate transport, involving pstSCAB and nptA, has been discovered to play a key role in NO resistance at alkaline pH conditions. The Delta pstS Delta nptA mutant shows attenuation under NO stress.