Genetic diversity and characteristics of high-level tigecycline resistance Tet(X) in Acinetobacter species
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RESEARCH
Open Access
Genetic diversity and characteristics of high-level tigecycline resistance Tet(X) in Acinetobacter species Chong Chen1,2,3, Chao-Yue Cui1,2,3, Jun-Jun Yu4, Qian He1,2,3, Xiao-Ting Wu1,2,3, Yu-Zhang He1,2,3, Ze-Hua Cui1,2,3, Cang Li1,2,3, Qiu-Lin Jia1,2,3, Xiang-Guang Shen3, Ruan-Yang Sun1,2,3, Xi-Ran Wang1,2,3, Min-Ge Wang1,2,3, Tian Tang1,2,3, Yan Zhang1,2,3, Xiao-Ping Liao1,2,3, Barry N. Kreiswirth5, Shi-Dan Zhou6, Bin Huang7, Hong Du8, Jian Sun1,2,3*, Liang Chen5,9* and Ya-Hong Liu1,2,3*
Abstract Background: The recent emergence and dissemination of high-level mobile tigecycline resistance Tet(X) challenge the clinical effectiveness of tigecycline, one of the last-resort therapeutic options for complicated infections caused by multidrug-resistant Gram-negative and Gram-positive pathogens. Although tet(X) has been found in various bacterial species, less is known about phylogeographic distribution and phenotypic variance of different genetic variants. Methods: Herein, we conducted a multiregional whole-genome sequencing study of tet(X)-positive Acinetobacter isolates from human, animal, and their surrounding environmental sources in China. The molecular and enzymatic features of tet(X) variants were characterized by clonal expression, microbial degradation, reverse transcription, and gene transfer experiments, while the tet(X) genetic diversity and molecular evolution were explored by comparative genomic and Bayesian evolutionary analyses. Results: We identified 193 tet(X)-positive isolates from 3846 samples, with the prevalence ranging from 2.3 to 25.3% in nine provinces in China. The tet(X) was broadly distributed in 12 Acinetobacter species, including six novel species firstly described here. Besides tet(X3) (n = 188) and tet(X4) (n = 5), two tet(X5) variants, tet(X5.2) (n = 36) and tet(X5.3) (n = 4), were also found together with tet(X3) or tet(X4) but without additive effects on tetracyclines. These tet(X)positive Acinetobacter spp. isolates exhibited 100% resistance rates to tigecycline and tetracycline, as well as high minimum inhibitory concentrations to eravacycline (2–8 μg/mL) and omadacycline (8–16 μg/mL). Genetic analysis revealed that different tet(X) variants shared an analogous ISCR2-mediated transposon structure. The molecular evolutionary analysis indicated that Tet(X) variants likely shared the same common ancestor with the chromosomal monooxygenases that are found in environmental Flavobacteriaceae bacteria, but sequence divergence suggested (Continued on next page)
* Correspondence: [email protected]; [email protected]; [email protected] 1 National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China 5 Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.
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