Universität zu Köln

Nowak, Jennifer, Schneiders, Thamarai ORCID: 0000-0002-7758-7925, Seifert, Harald and Higgins, Paul G. ORCID: 0000-0001-8677-9454 (2016). The Asp20-to-Asn Substitution in the Response Regulator AdeR Leads to Enhanced Efflux Activity of AdeB in Acinetobacter baumannii. Antimicrob. Agents Chemother., 60 (2). S. 1085 - 1091. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-6596

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Abstract

Overexpression of the resistance-nodulation-cell division-type efflux pump AdeABC is often associated with multidrug resistance in Acinetobacter baumannii and has been linked to mutations in the genes encoding the AdeRS two-component system. In a previous study, we reported that the Asp20 -> Asn amino acid substitution in the response regulator AdeR is associated with adeB overexpression and reduced susceptibility to the antimicrobials levofloxacin, tigecycline, and trimethoprim-sulfamethoxazole. To further characterize the effect of the Asp20 -> Asn substitution on antimicrobial susceptibility, the expression of the efflux genes adeB, adeJ, and adeG, and substrate accumulation, four plasmid constructs [containing adeR(Asp20) S, adeR(Asn20) S, adeR(Asp20) SABC, and adeR(Asn20) SABC] were introduced into the adeRSABC-deficient A. baumannii isolate NIPH 60. Neither adeRS construct induced changes in antimicrobial susceptibility or substrate accumulation from that for the vector-only control. The adeR(Asp20) SABC transformant showed reduced susceptibility to 6 antimicrobials and accumulated 12% less ethidium than the control, whereas the Asn20 variant showed reduced susceptibility to 6 of 8 antimicrobial classes tested, and its ethidium accumulation was only 72% of that observed for the vector-only construct. adeB expression was 7-fold higher in the adeR(Asn20) SABC transformant than in its Asp20 variant. No changes in adeG or adeJ expression or in acriflavine or rhodamine 6G accumulation were detected. The antimicrobial susceptibility data suggest that AdeRS does not regulate any resistance determinants other than AdeABC. Furthermore, the characterization of the Asp20 -> Asn20 substitution proves that the reduced antimicrobial susceptibility previously associated with this substitution was indeed caused by enhanced efflux activity of AdeB.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nowak, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneiders, Thamarai UNSPECIFIED orcid.org/0000-0002-7758-7925 UNSPECIFIED Seifert, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED Higgins, Paul G. UNSPECIFIED orcid.org/0000-0001-8677-9454 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-286070
DOI:	10.1128/AAC.02413-15
Journal or Publication Title:	Antimicrob. Agents Chemother.
Volume:	60
Number:	2
Page Range:	S. 1085 - 1091
Date:	2016
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-6596
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MULTIPLE ANTIBIOTIC-RESISTANCE; MULTIDRUG-RESISTANCE; ESCHERICHIA-COLI; 2-COMPONENT SYSTEM; PUMP; ADEABC; TIGECYCLINE; SUSCEPTIBILITY; MECHANISM; OVEREXPRESSION Multiple languages Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28607