Genetic Characterization of Enterobacter hormaechei Co-Harboring blaNDM-1 and mcr-9 Causing Upper Respiratory Tract Infection

Huiqiong Liu,1 Dao Wang,1 Miaomiao Tang,1 Peisheng Jia,1 Yufeng Huo,1 Erhu Wei,1 Hao Xu,2 Xiaohui Chi,2 Huaili Wang1 1Department of Pediatric Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Huaili Wang, Department of Pediatric Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, No. 1 Longhu East Zhonghuan Road, Zhengzhou, 450052, People’s Republic of China, Tel +86-371-66271057, Email whlek6527@126.comPurpose: With the spread of multiple drug-resistant bacteria, blaNDM-1 and mcr-9 have been detected in various bacteria worldwide. However, the simultaneous detection of blaNDM-1 and mcr-9 in Enterobacter hormaechei has been rarely reported. This study identified an E. hormaechei strain carrying both blaNDM-1 and mcr-9. We investigated the genetic characteristics of these two resistance genes in detail, elucidating various potential mechanisms by which they may be transmitted.Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) with Illumina and PacBio platforms and phylogenetic analysis. Subsequent investigations were performed, including antimicrobial susceptibility testing and multilocus sequence typing (MLST).Results: We isolated an E. hormaechei strain DY1901 carrying both blaNDM-1 and mcr-9 from the sputum sample. Susceptibility testing showed that the isolate was multidrug-resistant. Multiple antibiotic resistance genes and virulence genes are widely distributed in DY1901. S1-PFGE, Southern blotting, and plasmid replicon typing showed that DY1901 carried four plasmids. The plasmid carrying mcr-9 was 259Kb in size and belonged to IncHI2, while the plasmid carrying blaNDM-1 was 45Kb in length and belonged to IncX3.Conclusion: The E. hormaechei strain isolated in this study has a broad antibiotic resistance spectrum, posing a challenge to clinical treatment. Plasmids carrying mcr-9 are fusion plasmids, and those taking NDM are widely disseminated in China, suggesting that we should conduct routine genomic surveillance on such plasmids to curb the spread of drug-resistant bacteria in the region.Keywords: E. hormaechei, New Delhi metallo-β-lactamase, mcr-9, whole-genome sequencing, phylogenetic analysis