Identification of a novel circular DNA carrying blaNDM−1 gene in an extensive drug resistant Providencia huaxiensis strain
摘要
Providencia, as an opportunistic pathogen, can cause serious infections and increasingly poses a life-threatening risk to public health. Carbapenems were initially considered effective agents conquering such infectious; however, the emergence of carbapenem-resistant Providencia strains has been attributed to the rapid spread of carbapenemase genes. In this study, we first reported a uniquely blaNDM−1 genetic structure that can evolve ‘circular DNA’. Among 901 carbapenem-resistant Enterobacteriaceae strains examined, only one P. huaxiensis strain was identified using VITEK MS, 16S rRNA sequencing, average nucleotide identity (ANI) and the DNA–DNA hybridization (DDH). Susceptibility testing using the broth microdilution method revealed that the P. huaxiensis strain was highly resistant to carbapenems, cephalosporin, quinolone and aminoglycosides. By whole-genome sequencing (WGS) and large fragment PCRs, we characterized more than 7 resistance genes including blaNDM−1, blaOXA−10, qnrB, aadB, sul1, tetA and aadA1 in the P. huaxiensis strain PH1503, in which 2 copies of each the blaNDM−1 and blaOXA−10 genes were identified to be integrated into 3 plasmids. The blaNDM−1 gene was integrated into a novel structure of ISCR1-trpF-bleMBL-blaNDM−1-CatB3-Arr-3-DfrA27-AadA16-qacEdelta1-Sul1, which was present in both pPH1503-1-NDM and pPH1503-5-NDM. Moreover, the DNA sequences of the novel structure and pPH1503-5-NDM was 100% identical to each other, indicating that the novel structure may cyclize into a ‘circular DNA’. To the best of our knowledge, this is the first description of a circular DNA carrying the blaNDM−1 gene, which was identified in clinically isolated P. huaxiensis strains and appears to be stably maintained.