Work

Inner-membrane transporter genotype shapes susceptibility to non-lytic antimicrobials and bacterial fitness in Escherichia coli

Year: 2026

Type: preprint

Abstract: Intracellularly acting antibacterials must cross the bacterial inner membrane to reach their targets. Using an isogenic Escherichia coli MG1655 panel carrying single and double deletions of sbmA, ygdD and mdtM , we assessed susceptibility to bleomycin, Oncocin, Api88 and Bac7(1–17), together with growth in vitro and competitive colonisation in the streptomycin-treated mouse intestine. SbmA was the dominant susceptibility determinant, whereas YgdD contributed most strongly to bleomycin and Api88 susceptibility. Deletion of ygdD or sbmA increased the bleomycin MIC four- and sixteenfold, respectively, while loss of both increased it 128-fold. Either single deletion also increased the Api88 MIC by more than 32-fold, whereas deletion of mdtM caused an eightfold increase. Single mutants grew similarly to wild type, whereas Δ ygdD Δ sbmA and Δ ygdD Δ mdtM had significantly longer doubling times; the largest effect was a 37% increase in Δ ygdD Δ sbmA . In mice, Δ sbmA and Δ mdtM showed reduced late competitive persistence. These findings support a compound-specific network of inner-membrane proteins whose fitness consequences depend on genetic background and environment.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.64898/2026.09.04.749474

Authors: Elisabeth Dohmann Chang, Juliane Marie Jürgensen Engberg, Henrik Franzyk, Anders Løbner-Olesen, Jakob Frimodt-Møller

Institution: University of Copenhagen

Language: English

Topic: Bacterial Genetics and Biotechnology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: Villum Fonden