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Quantification of Plasmid-Mediated Antibiotic Resistance in an Experimental Evolution Approach

Quantification of Plasmid-Mediated Antibiotic Resistance in an Experimental Evolution Approach

Published on: December 14, 2019

Ceftriaxone-resistant Salmonella Typhi carries an IncI1-ST31 plasmid encoding CTX-M-15

Bilal Djeghout¹, Senjuti Saha^2,3, Mohammad Saiful Islam Sajib^2,3

¹Laboratory of Microbiology and Virology, Department of Biomedical Sciences, University of Sassari, V. le San Pietro 43/B, 07100 Sassari, Italy.

Journal of Medical Microbiology

|April 5, 2018

Abstract

Purpose:

Ceftriaxone is the drug of choice for typhoid fever and the emergence of resistant Salmonella Typhi raises major concerns for treatment. There are an increasing number of sporadic reports of ceftriaxone-resistant S. Typhi and limiting the risk of treatment failure in the patient and outbreaks in the community must be prioritized. This study describes the use of whole genome sequencing to guide outbreak identification and case management.

Methodology:

An isolate of ceftriaxone-resistant S. Typhi from the blood of a child taken in 2000 at the Popular Diagnostic Center, Dhaka, Bangladesh was subjected to whole genome sequencing, using an Illumina NextSeq 500 and analysis using Geneious software.Results/Key findings. Comparison with other ceftriaxone-resistant S. Typhi revealed an isolate from the Democratic Republic of the Congo in 2015 as the closest relative but no evidence of an outbreak. A plasmid belonging to incompatibility group I1 (IncI1-ST31) which included blaCTX-M-15 (ceftriaxone resistance) associated with ISEcp-1 was identified. High similarity (90 %) was seen with pS115, an IncI1 plasmid from S. Enteritidis, and with pESBL-EA11, an incI1 plasmid from E. coli (99 %) showing that S. Typhi has access to ceftriaxone resistance through the acquisition of common plasmids.

Conclusions:

The transmission of ceftriaxone resistance from E. coli to S. Typhi is of concern because of clinical resistance to ceftriaxone, the main stay of typhoid treatment. Whole genome sequencing, albeit several years after the isolation, demonstrated the success of containment but clinical trials with alternative agents are urgently required.

Insights

Ceftriaxone-resistant Salmonella Typhi is a growing concern. Whole genome sequencing helped identify resistance mechanisms and track potential outbreaks, highlighting the need for new typhoid fever treatments.

Area of Science:

Microbiology
Genomics
Infectious Diseases

Background:

Ceftriaxone is a primary treatment for typhoid fever.
Emerging resistance in Salmonella Typhi (S. Typhi) poses a significant public health threat.
Early detection and management of resistant strains are crucial to prevent treatment failures and community outbreaks.

Purpose of the Study:

To investigate the genetic basis of ceftriaxone resistance in a S. Typhi isolate.
To utilize whole genome sequencing (WGS) for identifying potential outbreaks and guiding case management.
To understand the transmission pathways of antimicrobial resistance genes.

Main Methods:

Whole genome sequencing of a ceftriaxone-resistant S. Typhi isolate from Bangladesh using Illumina NextSeq 500.
Bioinformatic analysis of the genome using Geneious software.
Comparative genomics to identify related strains and resistance determinants.

Main Results:

The study identified a ceftriaxone resistance gene (blaCTX-M-15) on an IncI1 plasmid within the S. Typhi isolate.
The plasmid showed high similarity to those found in E. coli and S. Enteritidis, indicating potential plasmid-mediated resistance transfer.
No evidence of a widespread outbreak was found, suggesting successful containment, though the isolate's closest relative was from 2015 in the Democratic Republic of the Congo.

Conclusions:

The acquisition of common plasmids carrying resistance genes like blaCTX-M-15 from other bacteria (e.g., E. coli) is a significant concern for S. Typhi.
WGS proved effective in characterizing the resistance mechanism and confirming containment, even retrospectively.
Urgent clinical trials for alternative typhoid fever treatments are necessary due to increasing ceftriaxone resistance.

Read full analysis

Keywords:

Bangladesh CTX-M-15 IncI1-ST31 plasmid Salmonella Typhi antibiotic resistance ceftriaxone resistance

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