Inner-membrane transporter genotype shapes susceptibility to non-lytic antimicrobials and bacterial fitness in Escherichia coli
Intracellularly acting antibacterials must cross the bacterial inner membrane to reach their targets in the cytoplasm. Using a panel of isogenic Escherichia coli strains with single, double and triple deletions of sbmA, ygdD and mdtM the susceptibility to bleomycin, Oncocin, Api88 and Bac7(1-17), was assessed together with bacterial fitness in vitro and in vivo during mouse intestinal…
Bacterial susceptibility to non-lytic antimicrobials is influenced by the genotype of inner-membrane transporters, according to a study on Escherichia coli. Researchers examined the impact of sbmA, ygdD, and mdtM gene deletions on the bacterium's response to bleomycin, Oncocin, Api88, and Bac7(1-17). SbmA emerged as the primary susceptibility factor, while ygdD significantly impacted bleomycin and Api88 resistance, and moderately influenced Oncocin and Bac7(1-17) resistance.
The combined absence of both sbmA and ygdD led to a substantial 128-fold increase in bleomycin MIC and a 37% rise in doubling time. Although single mutants exhibited no visible growth defect, certain triple mutants displayed significant growth issues. In mice models, sbmA and mdtM deletions reduced late competitive persistence, suggesting a context-dependent fitness cost for inner-membrane susceptibility determinants.
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