Authors

R. P. Lamers; C. R. Eade; A. J. Waring; A. L. Cole;A. M. Cole

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Abbreviated Journal Title

Antimicrob. Agents Chemother.

Keywords

RHESUS-MACAQUE LEUKOCYTES; THETA-DEFENSINS; HEMODIALYSIS-PATIENTS; CARRIAGE; INFECTION; PEPTIDE; HIV-1; OINTMENT; STRAIN; VIRUS; Microbiology; Pharmacology & Pharmacy

Abstract

Nasal colonization of Staphylococcus aureus is a risk factor for pathogenic autoinfection, particularly in postoperative patients and the immunocompromised. As such, standardized preoperative nasal decolonization of S. aureus has become a major consideration for the prevention of nosocomial infection. However, only a few treatment options for nasal decolonization are currently available, with resistance to these approaches already a concern. Here we have identified the macrocyclic theta-defensin analogue RC-101 as a promising anti-S. aureus agent for nasal decolonization. RC-101 exhibits bactericidal effects against S. aureus with the use of in vitro epithelium-free systems, while also preventing the pathogen's proliferation and attachment in an ex vivo human nasal epithelial cell adhesion model and an organotypic model of human airway epithelia. Peptide concentrations as low as 2.5 mu M elicited significant reductions in S. aureus growth in epithelium-free systems, with 10 mu M concentrations being completely bactericidal for all strains tested, including USA300. In ex vivo nasal colonization models, RC-101 significantly reduced adherence, survival, and proliferation of S. aureus on human nasal epithelia. Reductions in S. aureus viability were evident in these assays, with as little as 1 mu g of peptide per tissue, while 10 mu g of RC-101 completely prevented adhesion of all strains tested. Furthermore, RC-101 did not exhibit cellular toxicity to human nasal epithelia at concentrations up to 200 mu M, nor did it induce a proinflammatory response in these cells. Collectively, the findings of this study identify RC-101 as a potential preventative of S. aureus nasal colonization.

Journal Title

Antimicrobial Agents and Chemotherapy

Volume

55

Issue/Number

11

Publication Date

1-1-2011

Document Type

Article

Language

English

First Page

5338

Last Page

5346

WOS Identifier

WOS:000296375600054

ISSN

0066-4804

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