Document Detail


Rapid conversion of Pseudomonas aeruginosa to a spherical cell morphotype facilitates tolerance to carbapenems and penicillins but increases susceptibility to antimicrobial peptides.
MedLine Citation:
PMID:  24419348     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The Gram negative human pathogen Pseudomonas aeruginosa is able to tolerate 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 therapeutics to combat bacterial infections.
Authors:
Leigh G Monahan; Lynne Turnbull; Sarah R Osvath; Debra Birch; Ian G Charles; Cynthia B Whitchurch
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-13
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  -     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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