Pseudomonas Acts as a Reservoir of Novel Tigecycline Resistance Efflux Pump tmexC6D6-toprJ1b and tmexCD-toprJ Variants

Cheng-Zhen Wang; Xun Gao; Xin-Hong Liang; Lu-Chao Lv; Li-Tao Lu; Chao Yue; Xiao-Xiao Cui; Ke-Er Yang; Duo Lu; Jian-Hua Liu; Jun Yang

doi:10.1128/spectrum.00767-23

Microbiology Spectrum (Jun 2023)

Pseudomonas Acts as a Reservoir of Novel Tigecycline Resistance Efflux Pump tmexC6D6-toprJ1b and tmexCD-toprJ Variants

Cheng-Zhen Wang,
Xun Gao,
Xin-Hong Liang,
Lu-Chao Lv,
Li-Tao Lu,
Chao Yue,
Xiao-Xiao Cui,
Ke-Er Yang,
Duo Lu,
Jian-Hua Liu,
Jun Yang

Affiliations

Cheng-Zhen Wang: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Xun Gao: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Xin-Hong Liang: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Lu-Chao Lv: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Li-Tao Lu: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Chao Yue: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Xiao-Xiao Cui: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Ke-Er Yang: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Duo Lu: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Jian-Hua Liu: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Jun Yang: Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China

DOI: https://doi.org/10.1128/spectrum.00767-23
Journal volume & issue: Vol. 11, no. 3

Abstract

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ABSTRACT Several variants of the plasmid-carried tigecycline resistance gene cluster, tmexCD-toprJ, have been identified. This study characterized another novel variant, tmexC6D6-toprJ1b, located on the chromosome of environmental-origin Pseudomonas mendocina. TMexC6D6-TOprJ1 mediates resistance to multiple drugs, including tigecycline. The promoter activity of tmexC6D6-toprJ1b and negative transcriptional repression by the upstream regulator tnfxB6 are crucial for the expression of tmexC6D6-toprJ1b. tmexC6D6-toprJ1b was found in the plasmids or chromosomes of different Pseudomonas species from six countries. Two genetic backgrounds, class 1 integrons and int-carrying integrase units, were found adjacent to the tmexC6D6-toprJ1b gene cluster and might mediate the transfer of this novel efflux pump gene cluster in Pseudomonas. Further phylogenetic analysis revealed Pseudomonas as the major reservoir of tmexCD-toprJ variants, warranting closer monitoring in the future. IMPORTANCE Tigecycline is one of the treatment options for serious infections caused by multidrug-resistant bacteria, and tigecycline resistance has gained extensive attention. The emergence of a transferable tigecycline resistance efflux pump gene cluster, tmexCD-toprJ, severely challenged the efficiency of tigecycline. In this study, we identified another novel tmexCD-toprJ variant, tmexC6D6-toprJ1b, which could confer resistance to multiple classes of antibiotics, including tigecycline. Although tmexC6D6-toprJ1b was found only in Pseudomonas species, tmexC6D6-toprJ1b might spread to Enterobacteriaceae hosts via mobile genetic elements resembling those of other tmexCD-toprJ variants, compromising the therapeutic strategies. Meanwhile, novel transferable tmexCD-toprJ variants are constantly emerging and mostly exist in Pseudomonas spp., indicating Pseudomonas as the important hidden reservoir and origin of tmexCD-toprJ variants. Continuous monitoring and investigations of tmexCD-toprJ are urgent to control its spread.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

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