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Spreading Patterns of NDM-Producing Enterobacteriaceae in Clinical and Environmental Settings in Yangon, Myanmar
Yo Sugawara1, Yukihiro Akeda2,3, Hideharu Hagiya3
1Japan-Thailand Research Collaboration Center on Emerging and Re-emerging Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Japan y1yo2yo3@biken.osaka-u.ac.jp.
Abstract:
The spread of carbapenemase-producing Enterobacteriaceae (CPE), contributing to widespread carbapenem resistance, has become a global concern. However, the specific dissemination patterns of carbapenemase genes have not been intensively investigated in developing countries, including Myanmar, where NDM-type carbapenemases are spreading in clinical settings. In the present study, we phenotypically and genetically characterized 91 CPE isolates obtained from clinical (n = 77) and environmental (n = 14) samples in Yangon, Myanmar. We determined the dissemination of plasmids harboring genes encoding NDM-1 and its variants using whole-genome sequencing and plasmid analysis. IncFII plasmids harboring blaNDM-5 and IncX3 plasmids harboring blaNDM-4 or blaNDM-7 were the most prevalent plasmid types identified among the isolates. The IncFII plasmids were predominantly carried by clinical isolates of Escherichia coli, and their clonal expansion was observed within the same ward of a hospital. In contrast, the IncX3 plasmids were found in phylogenetically divergent isolates from clinical and environmental samples classified into nine species, suggesting widespread dissemination of plasmids via horizontal transfer. Half of the environmental isolates were found to possess IncX3 plasmids, and this type of plasmid was confirmed to transfer more effectively to recipient organisms at a relatively low temperature (25°C) compared to the IncFII plasmid. Moreover, various other plasmid types were identified harboring blaNDM-1, including IncFIB, IncFII, IncL/M, and IncA/C2, among clinical isolates of Klebsiella pneumoniae or Enterobacter cloacae complex. Overall, our results highlight three distinct patterns of the dissemination of blaNDM-harboring plasmids among CPE isolates in Myanmar, contributing to a better understanding of their molecular epidemiology and dissemination in a setting of endemicity.
Insights
Carbapenemase-producing Enterobacteriaceae (CPE) spread is a global threat. This study reveals distinct plasmid dissemination patterns of NDM carbapenemase genes in Myanmar, highlighting IncFII and IncX3 plasmids in clinical and environmental settings.
Area of Science:
- Molecular microbiology and infectious diseases
- Antimicrobial resistance epidemiology
- Genomics and plasmid biology
Background:
- Carbapenemase-producing Enterobacteriaceae (CPE) pose a significant global health challenge due to rising carbapenem resistance.
- Understanding the specific dissemination patterns of carbapenemase genes, particularly NDM-type, is crucial, especially in developing countries like Myanmar.
- Previous research has not extensively detailed the molecular epidemiology of these resistance genes in Myanmar's clinical settings.
Purpose of the Study:
- To phenotypically and genetically characterize CPE isolates from clinical and environmental sources in Yangon, Myanmar.
- To determine the dissemination patterns of plasmids carrying NDM carbapenemase genes and their variants.
- To investigate the role of different plasmid types in the spread of NDM carbapenemases in a real-world setting.
Main Methods:
- Isolation and characterization of 91 CPE isolates from clinical (n=77) and environmental (n=14) samples.
- Whole-genome sequencing and plasmid analysis to identify plasmid types and associated carbapenemase genes (blaNDM variants).
- Plasmid transfer experiments at different temperatures to assess transfer efficiency.
Main Results:
- IncFII plasmids carrying blaNDM-5 and IncX3 plasmids carrying blaNDM-4 or blaNDM-7 were the most prevalent.
- IncFII plasmids were mainly found in clinical Escherichia coli isolates, showing clonal expansion within a hospital ward.
- IncX3 plasmids were widespread across nine species in both clinical and environmental samples, demonstrating efficient horizontal transfer, particularly at 25°C.
Conclusions:
- Three distinct dissemination patterns of blaNDM-harboring plasmids were identified in CPE isolates in Myanmar.
- IncX3 plasmids exhibit efficient horizontal transfer, contributing to the widespread dissemination of NDM carbapenemases in diverse hosts and environments.
- The findings provide critical insights into the molecular epidemiology and dissemination of NDM carbapenemases in an endemic setting, informing public health strategies.
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