title: Beta-hemolysin promotes skin colonization by Staphylococcus aureus.
abstract: Colonization by Staphylococcus aureus is a characteristic feature of several inflammatory skin diseases and is often followed by epidermal damage and invasive infection. In this study, we investigated the mechanism of skin colonization by a virulent community-acquired methicillin-resistant S. aureus (CA-MRSA) strain, MW2, using a murine ear colonization model. MW2 does not produce a hemolytic toxin, beta-hemolysin (Hlb), due to integration of a prophage, Sa3mw, inside the toxin gene (hlb). However, we found that strain MW2 bacteria that had successfully colonized murine ears included derivatives that produced Hlb. Genome sequencing of the Hlb-producing colonies revealed that precise excision of prophage Sa3mw occurred, leading to reconstruction of the intact hlb gene in their chromosomes. To address the question of whether Hlb is involved in skin colonization, we constructed MW2-derivative strains with and without the Hlb gene and then subjected them to colonization tests. The colonization efficiency of the Hlb-producing mutant on murine ears was more than 50-fold greater than that of the mutant without hlb. Furthermore, we also showed that Hlb toxin had elevated cytotoxicity for human primary keratinocytes. Our results indicate that S. aureus Hlb plays an important role in skin colonization by damaging keratinocytes, in addition to its well-known hemolytic activity for erythrocytes.
authors.affiliation: Department of Bacteriology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katayama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Baba
authors.forename: Miwa
authors.initials: M
authors.lastname: Sekine
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramatsu
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004423:Ear; D005260:Female; D016680:Genome, Bacterial; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology / Q000473:pathology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation; D039002:Prophages / Q000502:physiology; D017422:Sequence Analysis, DNA; D012867:Skin / Q000382:microbiology*; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D013204:Staphylococcus Phages / Q000502:physiology; D014775:Virus Activation
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus