How mutations cause drug resistant typhoid bacteria

A range of mutations has led to antimicrobial resistance in many strains of typhoid bacteria, according to a new genetic study published today.

Typhoid fever remains a major public health concern worldwide, say authors of a study in *The Lancet Microbe*.

Dr Jason Andrews and colleagues at Stanford University, California, USA, explain there are around 11 million cases per year, largely in south Asia, but also sub-Saharan Africa, southeast Asia, and Oceania.

They point out: "The effectiveness of antimicrobial therapy has been threatened by the emergence and expansion of antimicrobial-resistant strains."

In particular, "The emergence of increasingly antimicrobial-resistant Salmonella enterica serovar Typhi (S Typhi) threatens to undermine effective treatment and control."

So, the team set out to understand where antimicrobial resistance in S Typhi is emerging and spreading.

They sequenced the genomes of 3,489 S Typhi strains from Nepal, Bangladesh, Pakistan, and India between 2014 and 2019. A global set of 4,169 S Typhi genome sequences from 1905 to 2018 were also examined.

The team found evidence of frequent international and intercontinental transfers of antimicrobial-resistant S Typhi.

"Independent acquisition of plasmids and homoplastic mutations conferring antimicrobial resistance have occurred repeatedly in multiple lineages of S Typhi, predominantly arising in south Asia before spreading to other regions," they report.

Dr Andrews commented: “The speed at which highly resistant strains of S. Typhi have emerged and spread in recent years is a real cause for concern, and highlights the need to urgently expand prevention measures, particularly in countries at greatest risk.

"At the same time, the fact resistant strains of S. Typhi have spread internationally so many times also underscores the need to view typhoid control, and antibiotic resistance more generally, as a global rather than local problem.”

Silva, K. E. D. et al. The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi: a genomic epidemiology study. 22 June 2022; doi: 10.1016/ S2666-5247(22)00093-3

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