When less is more: shortening the Lpp protein leads to increased vancomycin resistance in Escherichia coli.

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dc.citation.issue12
dc.citation.volume76
dc.contributor.authorWykes H
dc.contributor.authorLe VVH
dc.contributor.authorOlivera C
dc.contributor.authorRakonjac J
dc.coverage.spatialEngland
dc.date.accessioned2024-07-18T01:37:19Z
dc.date.available2024-07-18T01:37:19Z
dc.date.issued2023-12-01
dc.description.abstractVancomycin 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.
dc.description.confidentialfalse
dc.edition.editionDecember 2023
dc.format.pagination746-750
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/37749219
dc.identifier.citationWykes 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).
dc.identifier.doi10.1038/s41429-023-00658-3
dc.identifier.eissn1881-1469
dc.identifier.elements-typejournal-article
dc.identifier.issn0021-8820
dc.identifier.pii10.1038/s41429-023-00658-3
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/70223
dc.languageeng
dc.publisherSpringer Nature Limited
dc.publisher.urihttps://www.nature.com/articles/s41429-023-00658-3
dc.relation.isPartOfJ Antibiot (Tokyo)
dc.rights(c) 2023 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectVancomycin
dc.subjectEscherichia coli
dc.subjectVancomycin Resistance
dc.subjectFurazolidone
dc.subjectMicrobial Sensitivity Tests
dc.subjectAnti-Bacterial Agents
dc.subjectBacterial Outer Membrane Proteins
dc.subjectLipoproteins
dc.subjectEscherichia coli Proteins
dc.titleWhen less is more: shortening the Lpp protein leads to increased vancomycin resistance in Escherichia coli.
dc.typeJournal article
pubs.elements-id480625
pubs.organisational-groupOther
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