Carotenoid-related alteration of cell membrane fluidity impacts Staphylococcus aureus susceptibility to host defense peptides.
Carotenoid pigments of Staphylococcus aureus provide 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, and in vitro susceptibility 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-susceptible Staphylococcus aureus (MSSA) isogenic clinical strain set was used, including a parental isolate with an intact carotenoid biosynthetic operon (crtOPQMN) containing the crtM gene encoding early steps in staphyloxanthin biosynthesis, a crtM deletion mutant, and a crtMN multicopy plasmid-complemented variant. Compared to the parental and crtM knockout strains, the crtMN-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 of S. aureus to subvert nonoxidative host defenses mediated by cationic peptides, potentially by increasing target membrane rigidity.
Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA 90502, USA. nmishra@labiomed.org
Nagendra N
NN
Mishra
George Y
GY
Liu
Michael R
MR
Yeaman
Cynthia C
CC
Nast
Richard A
RA
Proctor
James
J
McKinnell
Arnold S
AS
Bayer
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects; D017576:Daptomycin / Q000494:pharmacology; D023082:Defensins / Q000378:metabolism / Q000494:pharmacology; D005227:Fatty Acids / Q000032:analysis; D006801:Humans; D008560:Membrane Fluidity / Q000187:drug effects* / Q000502:physiology; D008826:Microbial Sensitivity Tests; D009876:Operon / Q000235:genetics / Q000502:physiology; D010743:Phospholipids / Q000032:analysis; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D024341:Xanthophylls / Q000096:biosynthesis / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D023082:Defensins; D005227:Fatty Acids; D010743:Phospholipids; D024341:Xanthophylls; C031841:staphyloxanthin; D017576:Daptomycin