Universität zu Köln

Gerson, Stefanie, Nowak, Jennifer, Zander, Esther, Ertel, Julia, Wen, Yurong ORCID: 0000-0001-8730-5197, Krut, Oleg, Seifert, Harald and Higgins, Paul G. ORCID: 0000-0001-8677-9454 (2018). Diversity of mutations in regulatory genes of resistance-nodulationcell division efflux pumps in association with tigecycline resistance in Acinetobacter baumannii. J. Antimicrob. Chemother., 73 (6). S. 1501 - 1509. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

Objectives: To investigate the mechanisms of tigecycline resistance in isogenic Acinetobacter baumannii isolate pairs as well as 65 unique clinical A. baumannii isolates obtained during the MagicBullet clinical trial from Greece, Italy and Spain. Methods: A. baumannii isolates were subjected to WGS and the regulatory genes of resistance-nodulation-cell division (RND)-type efflux pumps were analysed. MICs were determined by agar dilution and the expression of RND-type efflux pumps was measured by semi-quantitative RT-PCR. Results: In isolate pairs, disruption of adeS or adeN by ISs increased adeB or adeJ expression and conferred increased resistance to at least three antimicrobial classes, respectively. The insertion of ISAba1 in adeN was observed in more than 30% of tested isolates and was the most prevalent IS. Furthermore, the insertion of ISAba125 and ISAba27 into adeN was observed for the first time in A. baumannii isolates. Besides ISs, several different mutations were observed in adeN (e.g. deletions and premature stop codons), all of which led to increased tigecycline MICs. Moreover, several amino acid substitutions were detected in AdeRS, AdeN and AdeL. Of note, the substitutions D21V, G25S and D26N in AdeR were found in multiple sequences and suggest a mutational hotspot. Conclusions: This study provides an insight into the different mechanisms associated with tigecycline resistance using a genomic approach and points out the importance of considering adeRS and adeN as markers for tigecycline-resistant A. baumannii isolates.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gerson, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Nowak, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Esther UNSPECIFIED UNSPECIFIED UNSPECIFIED Ertel, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Wen, Yurong UNSPECIFIED orcid.org/0000-0001-8730-5197 UNSPECIFIED Krut, Oleg UNSPECIFIED UNSPECIFIED UNSPECIFIED Seifert, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED Higgins, Paul G. UNSPECIFIED orcid.org/0000-0001-8677-9454 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-183400
DOI:	10.1093/jac/dky083
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	73
Number:	6
Page Range:	S. 1501 - 1509
Date:	2018
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ADERS 2-COMPONENT SYSTEM; DECREASED SUSCEPTIBILITY; ANTIMICROBIAL RESISTANCE; ANTIBIOTIC-RESISTANCE; MULTIDRUG-RESISTANCE; ADEABC; EXPRESSION; ISABA1; OVEREXPRESSION; MECHANISMS Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18340