Journal
NATURE MEDICINE
Volume 19, Issue 3, Pages 364-367Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3047
Keywords
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Funding
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID)
- US National Institutes of Health (NIH) [ZIA AI000904-10]
- National Natural Science Foundation of China [30900026, 81171623, 81261120387]
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Widespread antibiotic resistance among important bacterial pathogens such as Staphylococcus aureus(1) calls for alternative routes of drug development. Interfering with crucial virulence determinants is considered a promising new approach to control bacterial infection(2). Phenol-soluble modulins (PSMs) are peptide toxins with multiple key roles in pathogenesis(3-5) and have a major impact on the ability of highly virulent S. aureus to cause disease(3,6). However, targeting PSMs for therapeutic intervention is hampered by their multitude and diversity. Here we report that an ATP-binding cassette transporter with previously unknown function is responsible for the export of all PSMs, thus representing a single target for complete obstruction of PSM production. The transporter had a strong effect on virulence phenotypes, such as neutrophil lysis, and the extent of its effect on the development of S. aureus infection was similar to that of the sum of all PSMs. Notably, the transporter was essential for bacterial growth. Furthermore, it contributed to producer immunity toward secreted PSMs and defense against PSM-mediated bacterial interference. Our study reveals a noncanonical, dedicated secretion mechanism for an important class of toxins and identifies this mechanism as a comprehensive potential target for the development of drugs to efficiently inhibit the growth and virulence of pathogenic staphylococci.
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