Universität zu Köln

Lucassen, Kai ORCID: 0000-0002-6335-7731, Mueller, Carina, Wille, Julia, Xanthopoulou, Kyriaki ORCID: 0000-0001-8591-8184, Hackel, Meredith, Seifert, Harald and Higgins, Paul G. ORCID: 0000-0001-8677-9454 (2021). Prevalence of RND efflux pump regulator variants associated with tigecycline resistance in carbapenem-resistant Acinetobacter baumannii from a worldwide survey. J. Antimicrob. Chemother., 76 (7). S. 1724 - 1731. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lucassen, Kai UNSPECIFIED orcid.org/0000-0002-6335-7731 UNSPECIFIED Mueller, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wille, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Xanthopoulou, Kyriaki UNSPECIFIED orcid.org/0000-0001-8591-8184 UNSPECIFIED Hackel, Meredith UNSPECIFIED UNSPECIFIED UNSPECIFIED Seifert, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED Higgins, Paul G. UNSPECIFIED orcid.org/0000-0001-8677-9454 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-575558
DOI:	10.1093/jac/dkab079
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	76
Number:	7
Page Range:	S. 1724 - 1731
Date:	2021
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DECREASED SUSCEPTIBILITY; ANTIBIOTIC-RESISTANCE; MUTATION; ADEN Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57555