The Mechanism of Tigecycline Resistance in Acinetobacter baumannii under Sub-Minimal Inhibitory Concentrations of Tigecycline

被引:3
作者
Liu, Cunwei [1 ]
Liu, Jia [1 ]
Lu, Qinghui [1 ]
Wang, Ping [1 ]
Zou, Qinghua [1 ]
机构
[1] Peking Univ, Sch Basic Med Sci, Dept Microbiol, Beijing 100191, Peoples R China
基金
中国国家自然科学基金;
关键词
Acinetobacter baumannii; tigecycline; sub-minimal inhibitory concentration (sub-MIC) antibiotics; RND efflux pump; proteome; EVOLUTION;
D O I
10.3390/ijms25031819
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The presence of sub-minimal inhibitory concentration (sub-MIC) antibiotics in our environment is widespread, and their ability to induce antibiotic resistance is inevitable. Acinetobacter baumannii, a pathogen known for its strong ability to acquire antibiotic resistance, has recently shown clinical resistance to the last-line antibiotic tigecycline. To unravel the complex mechanism of A. baumannii drug resistance, we subjected tigecycline-susceptible, -intermediate, and -mildly-resistant strains to successive increases in sub-MIC tigecycline and ultimately obtained tigecycline-resistant strains. The proteome of both key intermediate and final strains during the selection process was analyzed using nanoLC-MS/MS. Among the more than 2600 proteins detected in all strains, we found that RND efflux pump AdeABC was associated with the adaptability of A. baumannii to tigecycline under sub-MIC pressure. qRT-PCR analysis also revealed higher expression of AdeAB in strains that can quickly acquire tigecycline resistance compared with strains that displayed lower adaptability. To validate our findings, we added an efflux pump inhibitor, carbonyl cyanide m-chlorophenyl hydrazine (CCCP), to the medium and observed its ability to inhibit tigecycline resistance in A. baumannii strains with quick adaptability. This study contributes to a better understanding of the mechanisms underlying tigecycline resistance in A. baumannii under sub-MIC pressure.
引用
收藏
页数:13
相关论文
共 18 条
[1]   Evolution of antibiotic resistance at non-lethal drug concentrations [J].
Andersson, Dan I. ;
Hughes, Diarmaid .
DRUG RESISTANCE UPDATES, 2012, 15 (03) :162-172
[2]   Correlation of Ciprofloxacin Resistance with the AdeABC Efflux System in Acinetobacter baumannii Clinical Isolates [J].
Ardebili, Abdollah ;
Lari, Abdolaziz Rastegar ;
Talebi, Malihe .
ANNALS OF LABORATORY MEDICINE, 2014, 34 (06) :433-438
[3]   Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America [J].
Boucher, Helen W. ;
Talbot, George H. ;
Bradley, John S. ;
Edwards, John E., Jr. ;
Gilbert, David ;
Rice, Louis B. ;
Scheld, Michael ;
Spellberg, Brad ;
Bartlett, John .
CLINICAL INFECTIOUS DISEASES, 2009, 48 (01) :1-12
[4]   An increasing threat in hospitals:: multidrug-resistant Acinetobacter baumannii [J].
Dijkshoorn, Lenie ;
Nemec, Alexandr ;
Seifert, Harald .
NATURE REVIEWS MICROBIOLOGY, 2007, 5 (12) :939-951
[5]   MASS SPECTROMETRY IN SYSTEMS BIOLOGY: AN OVERVIEW [J].
Feng, Xiaojun ;
Liu, Xin ;
Luo, Qingming ;
Liu, Bi-Feng .
MASS SPECTROMETRY REVIEWS, 2008, 27 (06) :635-660
[6]   Uncovering the mechanisms of Acinetobacter baumannii virulence [J].
Harding, Christian M. ;
Hennon, Seth W. ;
Feldman, Mario F. .
NATURE REVIEWS MICROBIOLOGY, 2018, 16 (02) :91-102
[7]  
Hasan MJ, 2017, MALAYS J PATHOL, V39, P277
[8]   Molecular mechanisms of antimicrobial resistance in Acinetobacter baumannii, with a special focus on its epidemiology in Lebanon [J].
Jamal, Sabah ;
Al Atrouni, Ahmad ;
Rafei, Rayane ;
Dabboussi, Fouad ;
Hamze, Monzer ;
Osman, Marwan .
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE, 2018, 15 :154-163
[9]   In Vitro Activity of Various Antibiotics in Combination with Tigecycline Against Acinetobacter baumannii: A Systematic Review and Meta-Analysis [J].
Li, Jian ;
Yang, Xianghai ;
Chen, Lidan ;
Duan, Xinran ;
Jiang, Zhihui .
MICROBIAL DRUG RESISTANCE, 2017, 23 (08) :982-993
[10]   Prevalence of RND efflux pump regulator variants associated with tigecycline resistance in carbapenem-resistant Acinetobacter baumannii from a worldwide survey [J].
Lucassen, Kai ;
Mueller, Carina ;
Wille, Julia ;
Xanthopoulou, Kyriaki ;
Hackel, Meredith ;
Seifert, Harald ;
Higgins, Paul G. .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2021, 76 (07) :1724-1730