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

Jasmine Morgan, Matthew Smith, Mark T. Mc Auley, View ORCID ProfileJ. Enrique Salcedo-Sora
doi: https://doi.org/10.1101/335505
Jasmine Morgan
1Department of Biology, Edge Hill University, St. Helens Road, Ormskirk, Lancashire, L39 4QP, UK
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Matthew Smith
2School of Health Sciences, Liverpool Hope University, Hope Park, L16 9JD, Liverpool, UK
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Mark T. Mc Auley
3Chemical Engineering Department, University of Chester, Thronton Science Park, CH2 4NU, Chester, UK
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J. Enrique Salcedo-Sora
4School of Health Sciences, Liverpool Hope University, Hope Park, L16 9JD, Liverpool, UK. Tel: (+44) 0151 2912184
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  • ORCID record for J. Enrique Salcedo-Sora
  • For correspondence: salcede@hope.ac.uk
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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.

Abbreviations
OCFM
folate one-carbon metabolism
5-FCL
5-formyltetrahydrofolate cyclo-ligase
TMP
trimethoprim
SMX
sulfamethoxazole
DMSO
dimethylsulfoxide
MIQE
Minimum information for publication of quantitative real-time PCR experiments;
GCV
glycine cleavage complex;
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Posted May 31, 2018.
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Disrupting folate metabolism alters the capacity of bacteria in exponential growth to develop persisters to antibiotics
Jasmine Morgan, Matthew Smith, Mark T. Mc Auley, J. Enrique Salcedo-Sora
bioRxiv 335505; doi: https://doi.org/10.1101/335505
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Disrupting folate metabolism alters the capacity of bacteria in exponential growth to develop persisters to antibiotics
Jasmine Morgan, Matthew Smith, Mark T. Mc Auley, J. Enrique Salcedo-Sora
bioRxiv 335505; doi: https://doi.org/10.1101/335505

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