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Abstract

We identified a small colony variant (SCV) of an amoxicillin/clavulanic acid-resistant derivative of a clinical isolate of from Malawi, which was selected for in a subinhibitory concentration of gentamicin. The SCV was auxotrophic for hemin and had impaired biofilm formation compared to the ancestral isolates. A single novel nucleotide polymorphism (SNP) in , which encodes a glutamyl-tRNA reductase that catalyses the initial step of porphyrin biosynthesis leading to the production of haem, was responsible for the SCV phenotype. We showed the SNP in resulted in a significant fitness cost to the isolate, which persisted even in the presence of hemin. However, the phenotype quickly reverted during sequential sub-culturing in liquid growth media. As is not found in mammalian cells, and disruption of the gene results in a significant fitness cost, it represents a potential target for novel drug development specifically for the treatment of catheter-associated urinary tract infections caused by .

Funding
This study was supported by the:
  • National Institute for Health Research (Award NIHR200632)
    • Principle Award Recipient: Adam P Roberts
  • Medical Research Council (Award MR/S004793/1)
    • Principle Award Recipient: Adam P Roberts
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/content/journal/micro/10.1099/mic.0.000962
2020-08-07
2024-04-23
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