Impact of Deficiencies in Branched-Chain Fatty Acids and Staphyloxanthin inStaphylococcus aureus

Abstract

Staphylococcus aureusis a well-known human pathogen with the ability to cause mild superficial skin infections to serious deep-tissue infections, such as osteomyelitis, pneumonia, and infective endocarditis. A key toS. aureusinfections and its pathogenicity is its ability to survive in adverse environments, especially at lower temperatures, by regulation of its cell membrane. Branched-chain fatty acids (BCFAs) and staphyloxanthin have been shown to regulate membrane fluidity and staphylococcal virulence. This study was conducted with the hypothesis that the simultaneous lack of BCFAs and staphyloxanthin will have a far greater implication on environmental survival and virulence ofS. aureus. Lack of a functional branched-chainα-keto acid dehydrogenase (BKD) enzyme because of a mutation in thelpdAgene led to a decrease in the production of BCFAs, membrane fluidity, slower growth, and poorin vivosurvival ofS. aureus. A mutation in thecrtMgene eliminated the production of staphyloxanthin but it did not affect membrane BCFA levels, fluidity, growth, orin vivosurvival. AcrtM:lpdAdouble mutant showed much slower growth and attenuation compared to individual mutants. The results of this study suggest that simultaneous targeting of the BCFA and staphyloxanthin biosynthetic pathways can be a strategy to controlS. aureusinfections.