Prevalence of RND efflux pump regulator variants associated with tigecycline resistance in carbapenem-resistant Acinetobacter baumannii from a worldwide survey
| Autor: | Julia Wille, Kyriaki Xanthopoulou, Kai Lucaßen, Harald Seifert, Paul G. Higgins, Carina Müller, Meredith Hackel |
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| Rok vydání: | 2021 |
| Předmět: |
Acinetobacter baumannii
Microbiology (medical) Microbial Sensitivity Tests Tigecycline medicine.disease_cause Bacterial Proteins Drug Resistance Multiple Bacterial Prevalence medicine Pharmacology (medical) Insertion sequence Gene Pharmacology Genetics Mutation biology Broth microdilution Membrane Transport Proteins biology.organism_classification Stop codon Anti-Bacterial Agents Infectious Diseases Carbapenems Efflux Cell Division medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 76:1724-1730 |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkab079 |
| Popis: | Objectives To determine the most common tigecycline resistance mechanisms in carbapenem-resistant Acinetobacter baumannii isolates obtained during the global Tigecycline Evaluation Surveillance Trial (TEST). Methods Tigecycline MICs were determined by broth microdilution. WGS was used to screen for the previously identified tigecycline resistance mechanisms, as well as mutations in resistance-nodulation-cell division (RND)-type efflux pump regulators. Results From a total 313 isolates, 113 genetically unique tigecycline-resistant isolates were analysed. The most frequent and worldwide distributed mechanism associated with tigecycline resistance was disruption of adeN, which encodes the repressor of the RND efflux pump AdeIJK, either by IS elements or nucleotide deletions causing premature stop codons. However, mutations leading to amino acid substitutions and disruption by IS elements within the two-component regulatory system adeRS, which regulates expression of the AdeABC efflux pump, correlate with higher tigecycline MICs, but these were found less frequently and were mainly restricted to Southern European countries. Furthermore, an altered version of tviB was identified in several tigecycline-resistant isolates that did not have putative resistance mutations within RND-type regulators. The resistance determinants tet(A) and tet(X), as well as resistance mutations in putative resistance determinants trm, plsC, rrf, msbA and genes encoding 30S ribosomal proteins, were not identified in any isolate. Conclusions The most prevalent tigecycline resistance mechanisms were caused by alterations in the regulators of RND-type efflux pumps. These data provide the basis for further characterization of regulator alterations and their contribution to increased efflux and tigecycline resistance, and also should be taken into account in drug discovery programmes to overcome the contribution of efflux pumps. |
| Databáze: | OpenAIRE |
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