title: Staphylococcus aureus hijacks a skin commensal to intensify its virulence: immunization targeting β-hemolysin and CAMP factor.
abstract: The need for a new anti-Staphylococcus aureus therapy that can effectively cripple bacterial infection, neutralize secretory virulence factors, and lower the risk of creating bacterial resistance is undisputed. Here, we propose what is, to our knowledge, a previously unreported infectious mechanism by which S. aureus may commandeer Propionibacterium acnes, a key member of the human skin microbiome, to spread its invasion and highlight two secretory virulence factors (S. aureus β-hemolysin and P. acnes CAMP (Christie, Atkins, Munch-Peterson) factor) as potential molecular targets for immunotherapy against S. aureus infection. Our data demonstrate that the hemolysis and cytolysis by S. aureus were noticeably augmented when S. aureus was grown with P. acnes. The augmentation was significantly abrogated when the P. acnes CAMP factor was neutralized or β-hemolysin of S. aureus was mutated. In addition, the hemolysis and cytolysis of recombinant β-hemolysin were markedly enhanced by recombinant CAMP factor. Furthermore, P. acnes exacerbated S. aureus-induced skin lesions in vivo. The combination of CAMP factor neutralization and β-hemolysin immunization cooperatively suppressed the skin lesions caused by coinfection of P. acnes and S. aureus. These observations suggest a previously unreported immunotherapy targeting the interaction of S. aureus with a skin commensal.
authors.affiliation: Division of Dermatology, Department of Medicine, University of California, San Diego, San Diego, California 92121, USA.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Lo
authors.forename: Yiu-Kay
authors.initials: YK
authors.lastname: Lai
authors.forename: Yu-Tsueng
authors.initials: YT
authors.lastname: Liu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Huang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006460:Hemolysin Proteins / Q000276:immunology* / Q000378:metabolism; D006461:Hemolysis / Q000502:physiology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D054892:Metagenome / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D011425:Propionibacterium acnes / Q000378:metabolism / Q000472:pathogenicity*; D012867:Skin / Q000382:microbiology* / Q000473:pathology; D013108:Sphingomyelin Phosphodiesterase / Q000276:immunology* / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus