Carotenoid-Related Alteration of Cell Membrane Fluidity ImpactsStaphylococcus aureusSusceptibility to Host Defense Peptides

Abstract

ABSTRACTCarotenoid pigments ofStaphylococcus aureusprovide integrity to its cell membrane (CM) and limit oxidative host defense mechanisms. However, the role of carotenoids in staphylococcal resistance to nonoxidative host defenses has not been characterized. The current study examined the relationship among CM carotenoid content, membrane order, andin vitrosusceptibility to daptomycin or to prototypic neutrophil-derived, platelet-derived, or bacterium-derived cationic antimicrobial peptides (human neutrophil defensin-1 [hNP-1], platelet microbicidal proteins [PMPs], or polymyxin B, respectively). A previously characterized methicillin-susceptibleStaphylococcus aureus(MSSA) isogenic clinical strain set was used, including a parental isolate with an intact carotenoid biosynthetic operon (crtOPQMN) containing thecrtMgene encoding early steps in staphyloxanthin biosynthesis, acrtMdeletion mutant, and acrtMNmulticopy plasmid-complemented variant. Compared to the parental andcrtMknockout strains, thecrtMN-complemented strain exhibited (i) increased carotenoid production, (ii) increased CM rigidity (P< 0.001), and (iii) uniformly reduced susceptibility to killing by the above-mentioned range of cationic peptides (statistically significant for hNP-1 [20 μg/ml];P= 0.0037). There were no significant differences in phospholipid composition and asymmetry, fatty acid profiles, surface charge, or cell wall thickness among the strain set. Collectively, these data support the concept that carotenoid biosynthesis can contribute to the ability ofS. aureusto subvert nonoxidative host defenses mediated by cationic peptides, potentially by increasing target membrane rigidity.