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An extended reservoir of class-D beta-lactamases in non-clinical bacterial strains
Open accessPreprint — published as 10.1128/spectrum.00315-22
Abstract
Bacterial genes coding for antibiotic resistance represent a major issue in the fight against bacterial pathogens. Among those, genes encoding beta-lactamases target penicillin and related compounds such as carbapenems, which are critical for human health. Beta-lactamases are classified into classes A, B, C and D, based on their amino acid sequence. Class D enzymes are also known as OXA beta-lactamases, due to the ability of the first enzymes described in this class to hydrolyze oxacillin. While hundreds of class D beta-lactamases with different activity profiles have been isolated from clinical strains, their nomenclature remains very uninformative. In this work, we have carried out a comprehensive survey of a reference database of 80,490 genomes and identified 24,916 OXA-domain containing proteins. These were deduplicated and their representative sequences clustered into 45 non-singleton groups derived from a phylogenetic tree of 1413 OXA-domain sequences, including five clusters that include the C-terminal domain of the BlaR membrane receptors. Interestingly, 801 known class D beta-lactamases fell into only 18 clusters. To probe the unknown diversity of the class, we selected ten protein sequences in ten uncharacterized clusters and studied the activity profile of the corresponding enzymes. A beta-lactamase activity could be detected for seven of them. Three enzymes were active against oxacillin and two against imipenem. These results indicate that, as already reported, environmental bacteria constitute a large reservoir of resistance genes that can be transferred to clinical strains, whether through plasmid exchange or hitchhiking with the help of transposase genes. Importance: The transmission of genes coding for resistance factors from environmental to nosocomial strains is a major component in the development of bacterial resistance towards antibiotics. Our survey of class D beta-lactamase genes in genomic databases highlighted the high sequence diversity of the enzymes that are able to recognize and/or hydrolyze beta-lactam antibiotics. Among those, we could also identify new beta-lactamases that are able to hydrolyze carbapenems, one of the last resort antibiotic families used in human chemotherapy. Therefore, it can be expected that the use of this antibiotic family will fuel the emergence of new beta-lactamases into clinically relevant strains.
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Metadata
- Authors
- Lupo, V., Mercuri, P. S., Frère, J.-M., Joris, B., Galleni, M., Baurain, D., & Kerff, F.
- Affiliations
- University of Liège (BE)
- Corresponding author
- Baurain, Denis
- Kerff, Frédéric
- Venue
- Microbiology Spectrum
- Publisher
- openRxiv
- Published
- 2022-01-21
- Volume
- 10
- Issue
- 2
- Pages
- e0031522-e0031522
- ISSN
- 2165-0497 (ISSN-L)
- PMC
- PMC9045261
- OpenAlex
- W4221037386
- Cited by
- 17
- References
- 1
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 1
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Microbiology Spectrum (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORBi (University of Liège) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fonds De La Recherche Scientifique - FNRS (CDR J.0080.15)
- Université de Liège (SFRD-12/04)
- FOD Volksgezondheid, Veiligheid van de Voedselketen en Leefmilieu (RF 17/6317 RU-BLA-ESBL-CPE)
- Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture
- Topics
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Physical Sciences › Environmental Science › Pollution › Pharmaceutical and Antibiotic Environmental Impacts
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- class D beta-lactamase, carbapenemase, beta-lactam resistance, environmental bacteria, horizontal gene transfer, sequence diversity, carbapenem resistance, antimicrobial resistance, nosocomial transmission
- MeSH terms
- Anti-Bacterial Agents, Bacteria, Bacterial Proteins, beta-Lactamases, Humans, Microbial Sensitivity Tests, Oxacillin, Phylogeny, Carbapenems
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