When less is more: shortening the Lpp protein leads to increased vancomycin resistance in Escherichia coli.
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Date
2023-12-01
Open Access Location
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Publisher
Springer Nature Limited
Rights
(c) 2023 The Author/s
CC BY 4.0
CC BY 4.0
Abstract
Vancomycin is a naturally occurring cell-wall-targeting glycopeptide antibiotic. Due to the low potency of this antibiotic against Gram-negative pathogens, such as Escherichia coli, there is a limited knowledge about interactions between vancomycin and this group of bacteria. Here, we show that an in-frame 63 bp deletion of the lpp gene caused a fourfold increase in vancomycin resistance in E. coli. The resulting protein, LppΔ21, is 21 amino acids shorter than the wild-type Lpp, a helical structural lipoprotein that controls the width of the periplasmic space through its length. The mutant remains susceptible to synergistic growth inhibition by combination of furazolidone and vancomycin; with furazolidone decreasing the vancomycin MIC by eightfold. These findings have clinical relevance, given that the vancomycin concentration required to select the lpp mutation is reachable during typical vancomycin oral administration for treating Clostridioides difficile infections. Combination therapy with furazolidone, however, is likely to prevent emergence and outgrowth of the lpp-mutated Gram-negative coliforms, avoiding exacerbation of the patient's condition during the treatment.
Description
Keywords
Humans, Vancomycin, Escherichia coli, Vancomycin Resistance, Furazolidone, Microbial Sensitivity Tests, Anti-Bacterial Agents, Bacterial Outer Membrane Proteins, Lipoproteins, Escherichia coli Proteins
Citation
Wykes H, Le VVH, Olivera C, Rakonjac J. (2023). When less is more: shortening the Lpp protein leads to increased vancomycin resistance in Escherichia coli.. J Antibiot (Tokyo). 76. 12. (pp. 746-750).