TY - JOUR T1 - Emergence of a novel mobile RND-type efflux pump gene cluster, <em>tmexC3D2-toprJ1b</em>, in <em>Pseudomonas</em> species JF - bioRxiv DO - 10.1101/2021.07.26.453812 SP - 2021.07.26.453812 AU - Shotaro Maehana AU - Ryotaro Eda AU - Nagi Niida AU - Aki Hirabayashi AU - Kouji Sakai AU - Takashi Furukawa AU - Kazunari Sei AU - Hidero Kitasato AU - Masato Suzuki Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/10/18/2021.07.26.453812.abstract N2 - 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 as tmexCD-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 of Pseudomonas alcaligenes were obtained from sewage water from a medical institution in Japan in 2020. Whole genome analysis of all P. alcaligenes isolates 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 of tmexCD-toprJ gene cluster, tmexC3D2-toprJ1b consisting of tmexC3, tmexC2, and toprJ1b, in phylogenetically clonal isolates of P. alcaligenes. The complete genome sequence of KAM426 revealed that this isolate co-harbors tmexC3D2-toprJ1b and two copies of the carbapenemase gene blaIMP-1 on the chromosome. tmexC3D2-toprJ1b in KAM426 was flanked by the IS5/IS1182 family transposase gene, suggesting that the gene cluster was acquired by horizontal gene transfer (HGT). tmexC3D2-toprJ1b seemed to have spread to other Pseudomonas species such as Pseudomonas aeruginosa via HGT mediated by mobile gene elements such as a plasmid. This study identified tmexCD-toprJ-like tigecycline resistance genes in Japan for the first time and suggests that diverse tmexCD-toprJ-like gene clusters, including tmexC3D2-toprJ1b, have spread among MDR-GNB worldwide. Further epidemiological genomic studies in clinical and environmental settings are needed.Competing Interest StatementThe authors have declared no competing interest. ER -