Abstract
Tigecycline serves as one of the last-resort antibiotics to treat severe infections caused by carbapenem-resistant Enterobacterales. Recently, a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, TmexCD1-ToprJ1, and its variants, TmexCD2-ToprJ2 and TmexCD3-ToprJ3, encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three TmexCD2-ToprJ2-harboring Klebsiella species strains, collected from two teaching tertiary hospitals in China, including one K. quasipneumoniae, one K. variicola, and one K. michiganensis. The three strains were characterized by antimicrobial susceptibility testing (AST), conjugation assay, WGS, and bioinformatics analysis. AST showed that K. variicola and K. quasipneumoniae strains were resistant to tigecycline with MIC values of 4μg/ml, whereas the K. michiganensis was susceptible to tigecycline with an MIC value of 1μg/ml. The TmexCD2-ToprJ2 clusters were located on three similar IncHI1B plasmids, of which two co-harbored the metallo-β-lactamase gene blaNDM-1. Conjugation experiments showed that all three plasmids were capable of self-transfer via conjugation. Our results showed, for the first time, that this novel plasmid-mediated tigecycline resistance mechanism TmexCD2-ToprJ2 has spread into different Klebsiella species, and clinical susceptibility testing may fail to detect. The co-occurrence of blaNDM-1 and TmexCD2-ToprJ2 in the same plasmid is of particular public health concern as the convergence of “mosaic” plasmids can confer both tigecycline and carbapenem resistance. Its further spread into other clinical high-risk Klebsiella clones will likely exacerbate the antimicrobial resistance crisis. A close monitoring of the dissemination of TmexCD-ToprJ encoding resistance should be considered.
Highlights
Tigecycline is one of the last-resort antibiotics used to treat severe infections caused by carbapenem-resistant Enterobacterales (Cheng et al, 2020)
In comparison with TmexCD1-ToprJ1, most of which were detected in K. pneumoniae (Figure 2), TmexCD2-ToprJ2 was identified among a variety of Enterobacteriaceae species, including R. ornithinolytica, C. freundii, Aeromonas hydrophila, and K. pneumoniae (Wang et al, 2021a)
Our study demonstrated that the TmexCD2-ToprJ2 had spread into carbapenem-resistant K. pneumoniae species complex (KpSC), which is an emerging pathogenic species and frequently detected clinically (Wyres et al, 2020)
Summary
Tigecycline is one of the last-resort antibiotics used to treat severe infections caused by carbapenem-resistant Enterobacterales (Cheng et al, 2020). Increasing studies reported the emergence of tigecycline resistance in clinical settings, which is frequently caused by the overexpression of non-specific active efflux pumps [tet(A) and tet(K)] or mutations within the drugbinding site in the ribosome [tet(M); Grossman, 2016; Linkevicius et al, 2016]. In Klebsiella pneumoniae, tigecycline resistance is frequently associated with the overexpression of ramA, which can directly regulate multidrug resistance efflux pumps AcrAB and OqxAB (Ruzin et al, 2005, 2008). These tigecycline resistances are primarily mediated by chromosome-encoding mechanisms could not be transferred horizontally. The enzymatic modification gene variants [tet(X)] are highly transferable between species (Linkevicius et al, 2016; He et al, 2019; Sun et al, 2019)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
