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Mechanisms involved in the active secretion of CTX-M-15 β-lactamase by pathogenic Escherichia coli ST131
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Rangama, Severine, Lidbury, Ian, Holden, Jennifer, Borsetto, Chiara, Murphy, Andrew, Hawkey, Peter and Wellington, E. M. H. (2021) Mechanisms involved in the active secretion of CTX-M-15 β-lactamase by pathogenic Escherichia coli ST131. Antimicrobial Agents and Chemotherapy, 65 (10). e0066321. doi:10.1128/AAC.00663-21
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WRAP-mechanisms-involved-active-secretion-CTX-M-15-β-lactamase-pathogenic-Escherichia-coli-ST131-2021.pdf - Accepted Version - Requires a PDF viewer. Download (1304Kb) | Preview |
Official URL: http://dx.doi.org/10.1128/AAC.00663-21
Abstract
Infections caused by antimicrobial-resistant bacterial pathogens are fast becoming an important global health issue. Strains of Escherichia coli are common causal agents of urinary tract infection and can carry multiple resistance genes. This includes the gene blaCTX-M-15, which encodes an extended-spectrum beta-lactamase (ESBL). While studying antimicrobial resistance (AMR) in the environment, we isolated several strains of E. coli ST131 downstream of a wastewater treatment plan (WWTP) in a local river. These isolates were surviving in the river sediment, and characterization proved that a multiresistant phenotype was evident. Here, we show that E. coli strain 48 (river isolate ST131) provided a protective effect against a third-generation cephalosporin (cefotaxime) for susceptible E. coli strain 33 (river isolate ST3576) through secretion of a functional ESBL into the growth medium. Furthermore, extracellular ESBL activity was stable for at least 24 h after secretion. Proteomic and molecular genetic analyses identified CTX-M-15 as the major secreted ESBL responsible for the observed protective effect. In contrast to previous studies, outer membrane vesicles (OMVs) were not the route for CTX-M-15 secretion. Indeed, mutation of the type I secretion system led to a significant reduction in the growth of the ESBL-producing strain as well as a significantly reduced ability to confer protective effect. We speculate that CTX-M-15 secretion, mediated through active secretion using molecular machinery, provides a public goods service by facilitating the survival of otherwise susceptible bacteria in the presence of cefotaxime.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
| Library of Congress Subject Headings (LCSH): | Escherichia coli, Escherichia coli -- Genetics, Escherichia coli infections , Drug resistance in microorganisms, Beta lactamases, Beta lactamases -- Inhibitors | ||||||
| Journal or Publication Title: | Antimicrobial Agents and Chemotherapy | ||||||
| Publisher: | American Society for Microbiology | ||||||
| ISSN: | 0066-4804 | ||||||
| Official Date: | 17 September 2021 | ||||||
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| Volume: | 65 | ||||||
| Number: | 10 | ||||||
| Article Number: | e0066321 | ||||||
| DOI: | 10.1128/AAC.00663-21 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||
| RIOXX Funder/Project Grant: |
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