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Lookup NU author(s): Professor Tracy Palmer FRS FRSE FMedSciORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The cell envelope of Gram-negative bacteria consists of two membranes surrounding the periplasm and peptidoglycan layer. β-lactam antibiotics target the periplasmic penicillin binding proteins that synthesize peptidoglycan resulting in cell death. The primary means by which bacterial species resist the effects of β-lactam drugs is to populate the periplasmic space with β-lactamases. Resistance to β-lactam drugs is spread by lateral transfer of genes encoding β-lactamases from one species of bacteria to another. However, the resistance phenotype depends in turn on these “alien” protein sequences being recognised and exported across the cytoplasmic membrane by either the Sec or Tat protein translocation machinery of the new bacterial host. Here we examine BKC-1, a carbapenemase from an unknown bacterial source that has been identified in a single clinical isolate of Klebsiella pneumoniae. BKC-1 was shown to be located in the periplasm, and functional in both K. pneumoniae and Escherichia coli. Sequence analysis revealed the presence of an unusual signal peptide with a twin arginine motif and a duplicated hydrophobic region. Biochemical assays showed that this signal peptide directs BKC-1 for translocation by both Sec and Tat translocons. This is one of the few descriptions of a periplasmic protein that is functionally translocated by both export pathways in the same organism, and we suggest it represents a snapshot of evolution for a b-lactamase adapting to functionality in a new host.
Author(s): Bharathwaj M, Webb CT, Vadlamani G, Stubenrauch CJ, Palmer T, Lithgow T
Publication type: Article
Publication status: Published
Journal: mBio
Year: 2021
Volume: 12
Issue: 3
Pages: e01302-21
Online publication date: 22/06/2021
Acceptance date: 11/05/2021
Date deposited: 14/05/2021
ISSN (print): 2161-2129
ISSN (electronic): 2150-7511
Publisher: American Society for Microbiology
URL: https://doi.org/10.1128/mBio.01302-21
DOI: 10.1128/mBio.01302-21
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