AUTHOR=Zhou Ying , Ai Wenxiu , Cao Yanhua , Guo Yinjuan , Wu Xiaocui , Wang Bingjie , Rao Lulin , Xu Yanlei , Zhao Huilin , Wang Xinyi , Yu Fangyou 

TITLE=The Co-occurrence of NDM-5, MCR-1, and FosA3-Encoding Plasmids Contributed to the Generation of Extensively Drug-Resistant Klebsiella pneumoniae

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 12 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.811263

DOI=10.3389/fmicb.2021.811263

ISSN=1664-302X

ABSTRACT=The rise and global dissemination of extensively drug-resistant (XDR) bacteria are often related to plasmid-borne mobile antimicrobial resistance genes. Notably, isolates having multiple plasmids are often highly resistant to almost all the antibiotics available. In this study, we characterized a multi-drug-resistant K. pneumoniae 1678, which exhibited high-level resistance to almost all the available antibiotics. Through whole-genome sequencing (WGS), more than 20 resistant elements and 5 resistance plasmids were observed. Notably, the tigecycline resistance of K. pneumoniae 1678 was not related to the plasmid-borne tetA gene but associated with the overexpression of AcrAB and OqxAB efflux pumps, according to the susceptibility results of tetA-transformant and the related mRNA quantification of RND efflux pumps. Expect for tigecycline resistance, three plasmids, mediating resistance to polymyxin B, fosfomycin, and ceftazidime–avibactam respectively, were focused. Detailed comparative genetic analysis showed that all these plasmids belonged to dominated epidemic plasmids, and harbored completed conjugation system. Results of conjugation assay indicated that these three plasmids not only could transfer to E. coli J53 with high conjugation frequencies respectively, but also could co-transfer to E. coli J53 smoothly, which were additionally confirmed by the S1-PFGE plasmids profile. Moreover, multiple insertion sequences (IS) and transposons (Tn) were also found surrounding the vital resistant genes, which may form several novel mechanisms involved in the resistant determinants’ mobilization. Overall, we report the uncommon co-existence and co-transferring of FosA3-, NDM-5 and MCR-1-encoding plasmids in a K. pneumoniae isolate, which greatly increased the risk of spread of these resistant phenotypes, and needing great concern.