Genetic diversity and characteristics of high-level tigecycline resistance Tet(X) in Acinetobacter species.

Autor: Chen C; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Cui CY; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Yu JJ; Guangdong Enterprise Key Laboratory for Animal Health and Environmental Control, WENS Foodstuff Group Co Ltd, Xinxing, China., He Q; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Wu XT; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., He YZ; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Cui ZH; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Li C; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Jia QL; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Shen XG; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Sun RY; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Wang XR; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Wang MG; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Tang T; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Zhang Y; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Liao XP; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China., Kreiswirth BN; Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA., Zhou SD; Intensive Care Unit, Huizhou Municipal Central Hospital, Huizhou, China., Huang B; Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Du H; Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China., Sun J; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China. jiansun@scau.edu.cn.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China. jiansun@scau.edu.cn.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China. jiansun@scau.edu.cn., Chen L; Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA. Liang.Chen@hmh-cdi.org.; Hackensack Meridian School of Medicine at Seton Hall University, Nutley, NJ, USA. Liang.Chen@hmh-cdi.org., Liu YH; National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China. lyh@scau.edu.cn.; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China. lyh@scau.edu.cn.; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China. lyh@scau.edu.cn.
Jazyk: angličtina
Zdroj: Genome medicine [Genome Med] 2020 Dec 07; Vol. 12 (1), pp. 111. Date of Electronic Publication: 2020 Dec 07.
DOI: 10.1186/s13073-020-00807-5
Abstrakt: 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 separation ~ 9900 years ago (7887 BC), presumably associated with the mobilization of tet(X)-like genes through horizontal transfer.
Conclusions: Four tet(X) variants were identified in this study, and they were widely distributed in multiple Acinetobacter spp. strains from various ecological niches across China. Our research also highlighted the crucial role of ISCR2 in mobilizing tet(X)-like genes between different Acinetobacter species and explored the evolutionary history of Tet(X)-like monooxygenases. Further studies are needed to evaluate the clinical impact of these mobile tigecycline resistance genes.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje