期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 58, 期 4, 页码 1956-1962出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01901-13
关键词
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资金
- Australian National Health and Medical Research Council [571905]
- ithree institute Postdoctoral Fellowship
- UTS Chancellor's Postdoctoral Fellowship
- National Health and Medical Research Council of Australia [571905] Funding Source: NHMRC
The Gram-negative human pathogen Pseudomonas aeruginosa tolerates high concentrations of beta-lactam antibiotics. Despite inhibiting the growth of the organism, these cell wall-targeting drugs exhibit remarkably little bactericidal activity. However, the mechanisms underlying beta-lactam tolerance are currently unclear. Here, we show that P. aeruginosa undergoes a rapid en masse transition from normal rod-shaped cells to viable cell wall-defective spherical cells when treated with beta-lactams from the widely used carbapenem and penicillin classes. When the antibiotic is removed, the entire population of spherical cells quickly converts back to the normal bacillary form. Our results demonstrate that these rapid population-wide cell morphotype transitions function as a strategy to survive antibiotic exposure. Taking advantage of these findings, we have developed a novel approach to efficiently kill P. aeruginosa by using carbapenem treatment to induce en masse transition to the spherical cell morphotype and then exploiting the relative fragility and sensitivity of these cells to killing by antimicrobial peptides (AMPs) that are relatively inactive against P. aeruginosa bacillary cells. This approach could broaden the repertoire of antimicrobial compounds used to treat P. aeruginosa and serve as a basis for developing new therapeutic agents to combat bacterial infections.
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