Hua, Xiaoting ORCID: 0000-0001-8215-916X, He, Jintao, Wang, Jingfen, Zhang, Linghong, Zhang, Linyue, Xu, Qingye, Shi, Keren, Leptihn, Sebastian ORCID: 0000-0002-4847-4622, Shi, Yue, Fu, Xiaoting, Zhu, Pengfei, Higgins, Paul G. ORCID: 0000-0001-8677-9454 and Yu, Yunsong (2021). Novel tigecycline resistance mechanisms in Acinetobacter baumannii mediated by mutations in adeS, rpoB and rrf. Emerg. Microbes Infect., 10 (1). S. 1404 - 1418. ABINGDON: TAYLOR & FRANCIS LTD. ISSN 2222-1751

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Abstract

Acinetobacter baumannii is an important pathogen in hospital acquired infections. Although tigecycline currently remains a potent antibiotic for treating infections caused by multidrug resistant A. baumannii (MDRAB) strains, reports of tigecycline resistant isolates have substantially increased. The resistance mechanisms to tigecycline in A. baumannii are far more complicated and diverse than what has been described in the literature so far. Here, we characterize in vitro-selected MDRAB strains obtained by increasing concentrations of tigecycline. We have identi?ed mutations in adeS, rrf and rpoB that result in reduced susceptibility to tigecycline. Using in situ complementation experiments, we confirm that mutations in rrf, rpoB, and two types of mutations in adeS correlate with tigecycline resistance. By Western blot and polysome profile analysis, we demonstrate that the rrf mutation results in decreased expression of RRF, which affects the process of ribosome recycling ultimately leading to increased tigecycline tolerance. A transcriptional analysis shows that the mutated rpoB gene plays a role in regulating the expression of the SAM-dependent methyltransferase (trm) and transcriptional regulators, to confer moderate tigecycline resistance. This study provides direct in vitro evidence that mutations in the adeS, rpoB and rrf are associated with tigecycline resistance in A. baumannii.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hua, XiaotingUNSPECIFIEDorcid.org/0000-0001-8215-916XUNSPECIFIED
He, JintaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, JingfenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, LinghongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, LinyueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xu, QingyeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shi, KerenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leptihn, SebastianUNSPECIFIEDorcid.org/0000-0002-4847-4622UNSPECIFIED
Shi, YueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fu, XiaotingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, PengfeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Higgins, Paul G.UNSPECIFIEDorcid.org/0000-0001-8677-9454UNSPECIFIED
Yu, YunsongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-592088
DOI: 10.1080/22221751.2021.1948804
Journal or Publication Title: Emerg. Microbes Infect.
Volume: 10
Number: 1
Page Range: S. 1404 - 1418
Date: 2021
Publisher: TAYLOR & FRANCIS LTD
Place of Publication: ABINGDON
ISSN: 2222-1751
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RIBOSOME RECYCLING FACTOR; DECREASED SUSCEPTIBILITY; ESCHERICHIA-COLI; STRUCTURAL BASIS; EF-G; PROTEIN; IDENTIFICATION; INFECTIONS; EXPRESSION; RIFAMPICINMultiple languages
Immunology; Infectious Diseases; MicrobiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59208

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