Co-Occurrence of mcr-9 and bla_NDM-1 in Enterobacter cloacae Isolated from a Patient with Bloodstream Infection

Abstract

Background

Bloodstream infection (BSI) caused by carbapenem-resistant Enterobacteriaceae are potentially life-threatening related to poorer outcomes. Colistin is considered one of the last-resort treatments against human infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Therefore, emergence of strains from the blood that co-harboring mcr and carbapenem resistance genes were considered as a serious problem.

Purpose

In this study, two mcr-9-harboring MDR Enterobacter cloacae isolates BSI034 and BSI072 recovered from BSI patients were identified, one of which co-harbored mcr-9 and bla_NDM-1. The genetic characteristics of the MDR plasmid needed to be clarified.

Methods

S1-PFGE and Southern blotting were conducted to determine the location of mcr-9. Whole-genome sequencing was performed to obtain the complete genome and plasmid sequences. The resistome and virulence genes of the strains, accompanied by the genetic characteristics of mcr-9- and bla_NDM-1-harboring plasmids, were analyzed.

Results

Whole-genome sequencing showed that BSI034 harbored mcr-9-carrying IncHI2-type pBSI034-MCR9 and bla_NDM-1-carrying IncX3-type pBSI034-NDM1. The 278,517 bp pBSI034-MCR9 carried mcr-9 along with the other 19 resistance genes. mcr-9 was flanked by IS903B (1057 bp) and IS26 (820 bp) in the same orientation. In addition to resistance genes, strain BSI034 also carried a chromosome-located Yersinia high-pathogenicity island, which harbored genes of yersiniabactin biosynthesis operon ybtSXQPAUTE, irp1/2, and fyuA.

Conclusion

We described the complete genome and mcr-9/bla_NDM-1-co-harboring plasmid of E. cloacae from a BSI patient. Notable differences were observed within mosaic modules between pBSI034-MCR9 and other mcr-9-harboring plasmids due to extensive recombination via horizontal gene transfer.

Keywords:

• MDR
• mcr-9
• colistin
• virulence genes

Acknowledgments

This work was supported by National Natural Science Foundation of China (81830103, 81722030, and 81902123), National Science and Technology Key Projects for Major Infectious Diseases (2017ZX10302301), China Postdoctoral Science Foundation (2019M653192), the Guangdong Natural Science Foundation (2017A030306012), the Science and Technology Planning Project of Guangdong (2017A020215017), Science, Technology & Innovation Commission of Shenzhen Municipality (JCYJ20190807151601699), Open project of Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Supported by the 111 Project, Grant No. B12003.

Disclosure

The authors report no conflicts of interest in this work.