Disrupting folate metabolism reduces the capacity of bacteria in exponential growth to develop persisters to antibiotics

Morgan, Jasmine and Smith, Matthew and Mc Auley, Mark T and Salcedo-Sora, J. Enrique (2018) Disrupting folate metabolism reduces the capacity of bacteria in exponential growth to develop persisters to antibiotics. Microbiology, 164 (11). pp. 1432-1445. ISSN 1350-0872

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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
both antibiotics ampicillin and ofloxacin. Persister bacteria were detectable from the outset of
the exponential growth phase in the complex media. Gene expression analyses showed
tentatively 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 antifolates could have a role to play
in clinical settings where the incidence of antibiotic persisters seem to drive recalcitrant
infections.

Item Type: Article
Additional Information and Comments: This is the author's version of an article that has been accepted for publication in Microbiology. The final, published version is available from http://mic.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.000722
Keywords: Antibiotic persistence, Recurrent infections, Folate, Antifolates, ampicillin, ofloxacin
Faculty / Department: Faculty of Science > School of Health Sciences
Depositing User: Enrique Salcedo-Sora
Date Deposited: 21 Sep 2018 10:46
Last Modified: 13 Nov 2018 10:15
URI: https://hira.hope.ac.uk/id/eprint/2603

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