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Published on: March 24, 2023
A large chromosomal inversion affects antimicrobial sensitivity of Escherichia coli to sodium deoxycholate
Vuong Van Hung Le1,2,3, Rayén Ignacia León-Quezada1, Patrick J Biggs1,4
1School of Natural Sciences, Massey University, Palmerston North, New Zealand.
Abstract:
Resistance to antimicrobials is normally caused by mutations in the drug targets or genes involved in antimicrobial activation or expulsion. Here we show that an Escherichia coli strain, named DOC14, selected for increased resistance to the bile salt sodium deoxycholate, has no mutations in any ORF, but instead has a 2.1 Mb chromosomal inversion. The breakpoints of the inversion are two inverted copies of an IS5 element. Besides lowering deoxycholate susceptibility, the IS5-mediated chromosomal inversion in the DOC14 mutant was found to increase bacterial survival upon exposure to ampicillin and vancomycin, and sensitize the cell to ciprofloxacin and meropenem, but does not affect bacterial growth or cell morphology in a rich medium in the absence of antibacterial molecules. Overall, our findings support the notion that a large chromosomal inversion can benefit bacterial cells under certain conditions, contributing to genetic variability available for selection during evolution. The DOC14 mutant paired with its isogenic parental strain form a useful model as bacterial ancestors in evolution experiments to study how a large chromosomal inversion influences the evolutionary trajectory in response to various environmental stressors.
Insights
A large chromosomal inversion in Escherichia coli, driven by IS5 elements, conferred resistance to bile salts and some antibiotics. This genetic rearrangement offers evolutionary advantages without impacting growth.
Area of Science:
- Microbiology
- Genetics
- Evolutionary Biology
Background:
- Antimicrobial resistance typically arises from mutations in drug targets or genes regulating drug metabolism.
- Chromosomal rearrangements, such as inversions, are less commonly recognized as a primary mechanism for antimicrobial resistance.
Purpose of the Study:
- To investigate the genetic basis of increased resistance to the bile salt sodium deoxycholate in an Escherichia coli strain.
- To determine the impact of a novel chromosomal inversion on antimicrobial susceptibility and bacterial fitness.
Main Methods:
- Selection of a resistant Escherichia coli strain (DOC14) to sodium deoxycholate.
- Whole-genome sequencing and comparative genomic analysis to identify genetic alterations.
- Phenotypic characterization of antimicrobial susceptibility and growth in vitro.
Main Results:
- A 2.1 Mb chromosomal inversion, flanked by inverted IS5 elements, was identified as the sole genetic difference in the DOC14 strain.
- The inversion reduced susceptibility to sodium deoxycholate, ampicillin, and vancomycin, while increasing susceptibility to ciprofloxacin and meropenem.
- No significant effect on bacterial growth or cell morphology was observed in rich medium without antibiotics.
Conclusions:
- Large chromosomal inversions can confer significant adaptive advantages, including altered antimicrobial resistance profiles.
- IS element-mediated rearrangements represent an important source of genetic variation driving bacterial evolution.
- The DOC14 mutant and its parent strain provide a valuable model for studying the evolutionary consequences of chromosomal inversions under selective pressures.
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