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A novel hemA mutation is responsible for a small-colony-variant phenotype in Escherichia coli

Hubbard, Alasdair ORCID:, Bulgasim, Issra and Roberts, Adam ORCID: (2021) 'A novel hemA mutation is responsible for a small-colony-variant phenotype in Escherichia coli'. Microbiology, Vol 167, Issue 3.

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We identified a small colony variant (SCV) of an amoxicillin/clavulanic acid-resistant derivative of a clinical isolate of Escherichia coli from Malawi, which was selected for in vitro 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 hemA, 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 hemA 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 hemA 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 E. coli.

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 450 General Works
QU Biochemistry > Genetics > QU 500 Genetic phenomena
QV Pharmacology > Anti-Bacterial Agents. Tissue Extracts > QV 350 Anti-bacterial agents (General or not elsewhere classified)
QW Microbiology and Immunology > Bacteria > QW 138 Enterobacteriaceae
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):
Depositing User: Cathy Waldron
Date Deposited: 10 Aug 2020 16:25
Last Modified: 06 Apr 2021 14:10


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