@article{e02a017551f0450a8f222ae8a83ec6c6,
title = "Ser253Leu substitution in PmrB contributes to colistin resistance in clinical Acinetobacter nosocomialis",
abstract = "Infections caused by extensively drug-resistant (XDR) Acinetobacter nosocomialis have become a challenging problem. The frequent use of colistin as the last resort drug for XDR bacteria has led to the emergence of colistin-resistant A. nosocomialis (ColRAN) in hospitals. The mechanism of colistin resistance in A. nosocomialis remains unclear. This study aimed to investigate the mechanisms underlying colistin resistance in clinical ColRAN isolates. We collected 36 A. nosocomialis isolates from clinical blood cultures, including 24 ColRAN and 12 colistin-susceptible A. nosocomialis (ColSAN). The 24 ColRAN isolates clustered with ST1272 (13), ST433 (eight), ST1275 (two), and ST410 (one) by multilocus sequence typing. There was a positive relationship between pmrCAB operon expression and colistin resistance. Further analysis showed that colistin resistance was related to an amino acid substitution, Ser253Leu in PmrB. By introducing a series of recombinant PmrB constructs into a PmrB knockout strain and protein structural model analyses, we demonstrated that the association between Ser253Leu and Leu244 in PmrB was coupled with colistin resistance in ColRAN. To the best of our knowledge, this is the first study demonstrating that the key amino acid Ser253Leu in PmrB is associated with overexpression of the pmrCAB operon and hence colistin resistance. This study provides insight into the mechanism of colistin resistance in A. nosocomialis.",
author = "Yang, {Ya Sung} and Jeng, {Wen Yih} and Lee, {Yi Tzu} and Hsu, {Chi Ju} and Chou, {Yu Ching} and Kuo, {Shu Chen} and Chen, {Cheng Cheung} and Hsu, {Wei Jane} and {the ACTION study group}, {ACTION study group} and Chen, {Hsing Yu} and Sun, {Jun Ren}",
note = "Funding Information: This work was supported by Ministry of National Defense: [Grant Number MND-MAB-107-090,MND-MAB-110-065,MND-MAB-D-111104]; Ministry of Science and Technology (MOST, Taiwan): [Grant Number MOST 107-2314-B-016-051-MY3,MOST 107-2314-B-075-066-MY3,MOST 108-2314-B-016-029,MOST 108-2320-B-016-009,MOST 108-2320-B038-053,MOST 109-2327-B-016-002,MOST 110-2314-B-016-062]; Taipei City Hospital: [Grant Number TPCH-109-20,TPCH-110-14]; Taipei Veterans General Hospital: [Grant Number V107C-037,V108C-012,VTA107-T-3-2,VTA108-T-2-2,VTA108-T-2-3]; Tri-Service General Hospital: [Grant Number TSGH-C109-144,TSGH-E-110204]. The members of the ACTION study group included Te-Li Chen (Graduate Institute of Life Sciences, NDMC), Yuag-Meng Liu (CCH), Po-Liang Lu (Kaoshiung Medical University Hospital), Chang-Pan Liu (MMH), Ya-Sung Yang (TSGH), Shu-Chen Kuo (the National Institute of Infectious Diseases and Vaccinology of the National Health Research Institute), Aristine Cheng (National Taiwan University Hospital), Yea-Yuan Chang (National Yang-Ming University Hospital), and Yi-Tzu Lee (TVGH). Funding Information: This work was supported by grants from the Ministry of National Defense (MND-MAB-107-090, MND-MAB-110-065 and MND-MAB-D-111104), Taipei City Hospital (TPCH-109-20 and TPCH-110-14), Taipei Veterans General Hospital (V107C-037, V108C-012, VTA107-T-3-2, VTA108-T-2-2, and VTA108-T-2-3), Tri-Service General Hospital (TSGH-C109-144 and TSGH-E-110204), and the Ministry of Science and Technology (MOST 107-2314-B-075-066-MY3, MOST 107-2314-B-016-051-MY3, MOST 108-2320-B038-053, MOST 108-2320-B-016-009, MOST 108-2314-B-016-029, MOST 109-2327-B-016-002 and MOST 110-2314-B-016-062). Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",
year = "2021",
doi = "10.1080/22221751.2021.1976080",
language = "English",
volume = "10",
pages = "1873--1880",
journal = "Emerging Microbes and Infections",
issn = "2222-1751",
publisher = "Nature Publishing Group",
number = "1",
}