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Tigecycline exhibits promising activity against multidrug-resistant Gram-negative bacteria (MDR-GNB), whose infections are difficult to treat with antimicrobials. However, mobile tigecycline resistance genes, such astmexCD-toprJ, have emerged in Enterobacterales isolated in China, Vietnam, and possibly other countries in the world. In this study, we investigated tigecycline-nonsusceptible GNB in Japan. Eight tigecycline- and carbapenem-nonsusceptible isolates ofPseudomonas alcaligeneswere obtained from sewage water from a medical institution in Japan in 2020. Whole genome analysis of allP. alcaligenesisolates was performed using short-read sequencing, and the isolate KAM426 was further analyzed using long-read sequencing. For important antimicrobial resistance genes, analysis of surrounding structures and comparison with similar sequences in the public genome database were performed. We identified a novel hybrid type oftmexCD-toprJgene cluster,tmexC3D2-toprJ1bconsisting oftmexC3,tmexC2, andtoprJ1b, in phylogenetically clonal isolates ofP. alcaligenes. The complete genome sequence of KAM426 revealed that this isolate co-harborstmexC3D2-toprJ1band two copies of the carbapenemase geneblaIMP-1on the chromosome.tmexC3D2-toprJ1bin KAM426 was flanked by the IS5/IS1182family transposase gene, suggesting that the gene cluster was acquired by horizontal gene transfer (HGT).tmexC3D2-toprJ1bseemed to have spread to otherPseudomonasspecies such asPseudomonas aeruginosavia HGT mediated by mobile gene elements such as a plasmid. This study identifiedtmexCD-toprJ-like tigecycline resistance genes in Japan for the first time and suggests that diversetmexCD-toprJ-like gene clusters, includingtmexC3D2-toprJ1b, have spread among MDR-GNB worldwide. Further epidemiological genomic studies in clinical and environmental settings are needed. |
