Detection of mobile colistin-resistance gene variants (mcr-1 and mcr-2) in urinary tract pathogens in Bangladesh: the last resort of infectious disease management colistin efficacy is under threat

ABSTRACT

Background: Currently, colistin-resistant pathogens emerged has become a global health concern. This study assessed the distribution of mcr-1 to mcr-5 variants with the phenotypic colistin-resistance in bacterial isolates from urinary tract infection (UTI) patients in Bangladesh.

Methods: A cross-sectional study was conducted between April 2017 and March 2018 to enroll uncomplicated UTI patients, and 142 urine samples were analyzed. Uropathogens were identified using the API-20E biochemical panel and 16s rRNA gene sequencing. Polymerase chain reactions detected the mcr gene variants in the UTI isolates. The phenotypic colistin-susceptibility was determined by the Kirby–Bauer disc-diffusion method and the minimal inhibitory concentration (MIC) measurement.

Results: The combined carriage of mcr-1 and mcr-2 genes in 11.4% (14/123) of urinary tract pathogens. The mcr-positive pathogens include five Escherichia coli, three Klebsiella pneumoniae, three Pseudomonas putida, two Enterobacter cloacae, and one Enterobacter hormaechei. The mcr-positive variant showed significantly higher phenotypic colistin resistance with MIC between >16 µg/mL and >128 µg/mL (p< 0.001). Over 85% of colistin-resistant isolates showed MDR phenomena.

Conclusions: The emergence of the clinical MDR pathogens with resistance to a highly selective drug may lead to a lack of treatment options for the infectious diseases and spread of infection to the unaffected cohorts.

KEYWORDS:

• Mobile colistin-resistance
• human-mcr
• urinary tract infections
• Bangladesh
• MDR

Article highlights

• The mobile colistin resistance gene variants, mcr-1 and mcr-2, were detected in UTI isolates of Bangladesh.

• Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas putida are the prominent UTI isolates reported of the mcr carriage.

• Uropathogens carrying the mcr variants showed significantly higher phenotypic colistin resistance with MIC values for colistin-sulfate ranging between >16 µg/mL and >128 µg/mL.

• Females were diagnosed with UTI more commonly than males. However, mcr genes were identified as a higher proportion in males compared to females.

• Among the mcr-positive uropathogens, 85% were found MDR that poses severe threats to colistin’s clinical utility, a last resort reserve drug.

Acknowledgments

The authors are grateful to M.S. Razzaque, of Lake Erie College of Osteopathic Medicine (Pennsylvania, USA), for providing useful suggestions.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Supplementary material

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Additional information

Funding

The research was supported partly from the Grants for Advanced Research in Education (GARE) funding, the Ministry of Education, Bangladesh, awarded to S. Islam (LS201685). The grant provided support for study design, data collection, and part of the laboratory investigation, but not manuscript publication. This study was further supported by a research grant from the Bangladesh Academy of Sciences and the United States Department of Agriculture (BAS-USDA) awarded to S. Islam and S. Nahar (Award ID: BAS-USDA HN-28/2020). The latter grant has provided support for partial laboratory investigation. The authors would like to thank the Award bodies and study participants for their active supports.