Rapid conversion of Pseudomonas aeruginosa to a spherical cell morphotype facilitates tolerance to carbapenems and penicillins but increases susceptibility to antimicrobial peptides

Monahan, Leigh G., Turnbull, Lynne, Osvath, Sarah R., Birch, Debra, Charles, Ian G. and Whitchurch, Cynthia B. ORCID: https://orcid.org/0000-0003-2296-3791 (2014) Rapid conversion of Pseudomonas aeruginosa to a spherical cell morphotype facilitates tolerance to carbapenems and penicillins but increases susceptibility to antimicrobial peptides. Antimicrobial Agents and Chemotherapy, 58 (4). pp. 1956-1962. ISSN 0066-4804

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Abstract

The Gram-negative human pathogen Pseudomonas aeruginosa tolerates high concentrations of β-lactam antibiotics. Despite inhibiting the growth of the organism, these cell wall-targeting drugs exhibit remarkably little bactericidal activity. However, the mechanisms underlying β-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 β-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.

Item Type: Article
Uncontrolled Keywords: pharmacology (medical),pharmacology,infectious diseases,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2736
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 11 Jun 2019 16:30
Last Modified: 22 Oct 2022 04:49
URI: https://ueaeprints.uea.ac.uk/id/eprint/71331
DOI: 10.1128/AAC.01901-13

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