title: A novel chimeric lysin shows superiority to mupirocin for skin decolonization of methicillin-resistant and -sensitive Staphylococcus aureus strains.
abstract: Staphylococcus aureus is a major human pathogen responsible for a number of serious and sometimes fatal infections. One of its reservoirs on the human body is the skin, which is known to be a source of invasive infection. The potential for an engineered staphylococcus-specific phage lysin (ClyS) to be used for topical decolonization is presented. We formulated ClyS into an ointment and applied it to a mouse model of skin colonization/infection with S. aureus. Unlike the standard topical antibacterial agent mupirocin, ClyS eradicated a significantly greater number of methicillin-susceptible S. aureus (MSSA) and -resistant S. aureus (MRSA) bacteria: a 3-log reduction with ClyS as opposed to a 2-log reduction with mupirocin in our model. The use of ClyS also demonstrated a decreased potential for the development of resistance by MRSA and MSSA organisms compared to that from the use of mupirocin in vitro. Because antibodies may affect enzyme function, we tested antibodies developed after repeated ClyS exposure for their effect on ClyS killing ability. Our results showed no inhibition of ClyS activity at various antibody titers. These data demonstrate the potential of developing ClyS as a novel class of topical antimicrobial agents specific to staphylococcus.
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY 10065, USA. mpastagia@rockefeller.edu
authors.forename: Mina
authors.initials: M
authors.lastname: Pastagia
authors.forename: Chad
authors.initials: C
authors.lastname: Euler
authors.forename: Peter
authors.initials: P
authors.lastname: Chahales
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Fischetti
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D005260:Female; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D051379:Mice; D008807:Mice, Inbred BALB C; D009088:Mucoproteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D016712:Mupirocin / Q000494:pharmacology / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D012867:Skin / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology; D013204:Staphylococcus Phages; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D009088:Mucoproteins; D011993:Recombinant Fusion Proteins; C010393:lysin, gastropoda; D016712:Mupirocin