Abstract
Typhoid fever, caused by Salmonella enterica serovar Typhi, remains an important public health burden in Southeast Asia and other endemic countries. Various genotyping methods have been applied to study the genetic variations of this human-restricted pathogen. Multilocus sequence typing (MLST) is one of the widely accepted methods, and recently, there is a growing interest in the re-application of MLST in the post-genomic era. In this study, we provide the global MLST distribution of S. Typhi utilizing both publicly available 1,826 S. Typhi genome sequences in addition to performing conventional MLST on S. Typhi strains isolated from various endemic regions spanning over a century. Our global MLST analysis confirms the predominance of two sequence types (ST1 and ST2) co-existing in the endemic regions. Interestingly, S. Typhi strains with ST8 are currently confined within the African continent. Comparative genomic analyses of ST8 and other rare STs with genomes of ST1/ST2 revealed unique mutations in important virulence genes such as flhB, sipC, and tviD that may explain the variations that differentiate between seemingly successful (widespread) and unsuccessful (poor dissemination) S. Typhi populations. Large scale whole-genome phylogeny demonstrated evidence of phylogeographical structuring and showed that ST8 may have diverged from the earlier ancestral population of ST1 and ST2, which later lost some of its fitness advantages, leading to poor worldwide dissemination. In response to the unprecedented increase in genomic data, this study demonstrates and highlights the utility of large-scale genome-based MLST as a quick and effective approach to narrow the scope of in-depth comparative genomic analysis and consequently provide new insights into the fine scale of pathogen evolution and population structure.
Highlights
Typhoid fever poses a significant health threat to many endemic countries
Our findings showed that ST1 and ST2 have been homogenously circulating for over the period of 109 years and represent the current predominant populations globally
We found no association between sequence types (STs) and
Summary
Typhoid fever poses a significant health threat to many endemic countries. Typhi), the etiologic agent, can be transmitted through contaminated food and water via the oral-fecal route. Over 21 million cases and nearly 200, 000 deaths are reported worldwide (Crump and Mintz, 2010). Despite major treatment and prevention efforts, MLST and WGS of S. Typhi global typhoid cases remain very high (Lozano et al, 2010; Murray et al, 2010). The disease is human restricted and the infected individuals could persist as long-term carriers, which in turn serve as the reservoir for new infections and outbreaks (Gonzalez-Escobedo et al, 2010)
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