When less is more: shortening the Lpp protein leads to increased vancomycin resistance in Escherichia coli
File(s)
Published version
Author(s)
Wykes, Hannah
Le, Vuong Van Hung
Olivera, Catrina
Rakonjac, Jasna
Type
Journal Article
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.
Date Issued
2023-12-01
Date Acceptance
2023-09-11
Citation
The Journal of Antibiotics, 2023, 76 (12), pp.746-750
ISSN
0021-8820
Publisher
Springer Science and Business Media LLC
Start Page
746
End Page
750
Journal / Book Title
The Journal of Antibiotics
Volume
76
Issue
12
Copyright Statement
© The Author(s) 2023. This article is published with open access Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Publication Status
Published
Date Publish Online
2023-09-25