1887

Abstract

When cultured together under standard laboratory conditions has been shown to be an effective inhibitor of . However, and are commonly observed in coinfections of individuals with cystic fibrosis (CF) and in chronic wounds. Previous work from our group revealed that isolates from CF infections are able to persist in the presence of strain PAO1 with a range of tolerances with some isolates being eliminated entirely and others maintaining large populations. In this study, we designed a serial transfer, evolution experiment to identify mutations that allow to survive in the presence of . Using USA300 JE2 as our ancestral strain, populations of were repeatedly cocultured with fresh PAO1. After eight coculture periods, populations that survived better in the presence of PAO1 were observed. We found two independent mutations in the highly conserved aspartate transporter, , that were unique to evolved -tolerant isolates. Subsequent phenotypic testing demonstrated that mutants have reduced uptake of glutamate and outcompeted wild-type when glutamate was absent from chemically defined media. These findings together demonstrate that the presence of exerts selective pressure on to alter its uptake and metabolism of key amino acids when the two are cultured together.

Funding
This study was supported by the:
  • Swiss National Science Foundation (Award PZ00P3_202186)
    • Principle Award Recipient: Simonvan Vliet
  • Cystic Fibrosis Foundation (Award GOLDBE19I0)
    • Principle Award Recipient: JoannaB Goldberg
  • National Institutes of Health (Award R21AI148847)
    • Principle Award Recipient: JoannaB Goldberg
  • National Institutes of Health (Award T32AI138952)
    • Principle Award Recipient: AshleyAlexander
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2024-03-01
2024-04-27
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