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Disrupting folate metabolism reduces the capacity of bacteria in exponential growth to develop persisters to antibiotics
Morgan, Jasmine Smith, Matthew Mc Auley, Mark T. Salcedo-Sora, J. Enrique
Morgan, Jasmine
Smith, Matthew
Mc Auley, Mark T.
Salcedo-Sora, J. Enrique
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Publication Date
2018-11-24
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Abstract
Bacteria can survive high doses of antibiotics through stochastic phenotypic diversification. We present initial evidence that folate metabolism could be involved with the formation of persisters. The aberrant expression of the folate enzyme gene fau seems to reduce the incidence of persisters to antibiotics. Folate-impaired bacteria had a lower generation rate for persisters to the antibiotics ampicillin and ofloxacin. Persister bacteria were detectable from the outset of the exponential growth phase in the complex media. Gene expression analyses tentatively showed distinctive profiles in exponential growth at times when bacteria persisters were observed. Levels of persisters were assessed in bacteria with altered, genetically and pharmacologically, folate metabolism. This work shows that by disrupting folate biosynthesis and usage, bacterial tolerance to antibiotics seems to be diminished. Based on these findings there is a possibility that bacteriostatic antibiotics such as anti-folates could have a role to play in clinical settings where the incidence of antibiotic persisters seems to drive recalcitrant infections.
Citation
Morgan, J., Smith, M., & Mc Auley, M. T., & Salcedo-Sora, E. (2018). Disrupting folate metabolism reduces the capacity of bacteria in exponential growth to develop persisters to antibiotics. Microbiology, 164, pp. 1432-1445. https://dx.doi.org/10.1099/mic.0.000722
Publisher
Microbiology Society
Journal
Microbiology
Research Unit
DOI
10.1099/mic.0.000722
PubMed ID
PubMed Central ID
Type
Article
Language
en
Description
This is an Accepted Manuscript of an article published by Microbiology Society in Microbiology on 1st November 2018, available online: https://dx.doi.org/10.1099/mic.0.000722
Series/Report no.
ISSN
EISSN
1465-2080