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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Multidrug-resistant conjugative plasmid carrying mphA confers increased antimicrobial resistance in Shigella
Asaduzzaman Asad1, Israt Jahan1, Moriam Akter Munni1
1Laboratory of Gut-Brain Axis, Infectious Diseases Division (IDD), icddr,b, 68, Shaheed Tajuddin Ahmad Sarani, Mohakhali, Dhaka, 1212, Bangladesh.
Abstract:
Shigellosis remains a common gastrointestinal disease mostly in children < 5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.
Insights
Antimicrobial resistance in Shigella is rising rapidly in Bangladesh, with macrolide resistance increasing significantly due to the mphA gene and horizontal gene transfer. This threatens effective treatment for childhood shigellosis.
Area of Science:
- Microbiology
- Infectious Diseases
- Public Health
Background:
- Shigellosis is a significant gastrointestinal illness in children under five in developing nations.
- Azithromycin (macrolide), ciprofloxacin, and ceftriaxone are frequently used antibiotics for shigellosis in Bangladesh.
Purpose of the Study:
- To investigate the current epidemiology of antimicrobial resistance (AMR) in Shigella isolates.
- To understand the mechanisms behind the increasing macrolide resistance in Shigella.
Main Methods:
- Analysis of 2407 clinical Shigella isolates from 2009 to 2016.
- Monitoring the prevalence of Shigella species (S. sonnei and S. flexneri).
- Determination of antibiotic resistance patterns and identification of resistance genes (mphA) and plasmids.
Main Results:
- Shigella sonnei became predominant over Shigella flexneri by 2016.
- Azithromycin resistance rose from 22% to ~60%, ciprofloxacin resistance by 40%, and ceftriaxone resistance from 0% to 15% between 2009-2016.
- The mphA gene on a conjugative plasmid was identified as the primary macrolide resistance mechanism, with rapid spread via horizontal gene transfer.
Conclusions:
- A sharp increase in resistance to azithromycin, ciprofloxacin, and ceftriaxone was observed, particularly after 2014.
- Horizontal gene transfer facilitates the rapid dissemination of macrolide resistance genes in Shigella.
- The rising AMR poses a significant threat to shigellosis treatment in Bangladesh.
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