Genome sequencing and analysis of Salmonella enterica serovar Typhi strain CR0063 representing a carrier individual during an outbreak of typhoid fever in Kelantan, Malaysia

Baddam, Ramani; Kumar, Narender; Shaik, Sabiha; Tiruvayipati, Suma; Ngoi, Soo Tein; Thong, Kwai Lin; Ahmed, Niyaz

doi:10.1186/1757-4749-4-20

Cited by 9 publications

(7 citation statements)

References 60 publications

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“…However, it remains obscure to what extent these variations are true in a larger population, or perhaps the variants are gradually displaced by the seemingly more successful and dominant strains due to selective pressures. To capture fine variations representing strains from different clinical outcomes, our research group has sequenced strains associated with sporadic cases , outbreak and human carrier from Malaysia .…”

Section: Early S Typhi Genome Sequencingmentioning

confidence: 99%

Salmonella Typhi genomics: envisaging the future of typhoid eradication

Yap

Thong

2017

Tropical Med Int Health

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SummaryNext-generation whole-genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding have transformed the field of molecular microbiology, epidemiology, infection treatments and vaccine developments. We review the key findings of the publicly accessible genomes of Salmonella enterica serovar Typhi since the first complete genome to the most recent release of thousands of Salmonella Typhi genomes, which remarkably shape the genomic research of S. Typhi and other pathogens. Important new insights acquired from the genome sequencing of S. Typhi, pertaining to genomic variations, evolution, population structure, antibiotic resistance, virulence, pathogenesis, disease surveillance/investigation and disease control are discussed. As the numbers of sequenced genomes are increasing at an unprecedented rate, fine variations in the gene pool of S. Typhi are captured in high resolution, allowing deeper understanding of the pathogen's evolutionary trends and its pathogenesis, paving the way to bringing us closer to eradication of typhoid through effective vaccine/treatment development.

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Section: Early S Typhi Genome Sequencingmentioning

confidence: 99%

Salmonella Typhi genomics: envisaging the future of typhoid eradication

Yap

Thong

2017

Tropical Med Int Health

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“…S . Typhi carriage isolates have been previously genetically compared to isolates from acute infections, with the aim of identifying signatures associated with carriage [ 20 – 23 ]. However, these studies were unable to infer how carriage isolates directly relate to those causing acute disease.…”

Section: Introductionmentioning

confidence: 99%

Gallbladder carriage generates genetic variation and genome degradation in Salmonella Typhi

et al. 2020

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Despite recent advances in typhoid fever control, asymptomatic carriage of Salmonella Typhi in the gallbladder remains poorly understood. Aiming to understand if S . Typhi becomes genetically adapted for long-term colonisation in the gallbladder, we performed whole genome sequencing on a collection of S . Typhi isolated from the gallbladders of typhoid carriers. These sequences were compared to contemporaneously sampled sequences from organisms isolated from the blood of acute patients within the same population. We found that S . Typhi carriage was not restricted to any particular genotype or conformation of antimicrobial resistance genes, but was largely reflective of S . Typhi circulating in the general population. However, gallbladder isolates showed a higher genetic variability than acute isolates, with median pairwise SNP distances of 21 and 13 SNPs ( p = 2.8x10 -9 ), respectively. Within gallbladder isolates of the predominant H58 genotype, variation was associated with a higher prevalence of nonsense mutations. Notably, gallbladder isolates displayed a higher frequency of non-synonymous mutations in genes encoding hypothetical proteins, membrane lipoproteins, transport/binding proteins, surface antigens, and carbohydrate degradation. Specifically, we identified several gallbladder-specific non-synonymous mutations involved in LPS synthesis and modification, with some isolates lacking the Vi capsular polysaccharide vaccine target due to the 134Kb deletion of SPI-7. S . Typhi is under strong selective pressure in the human gallbladder, which may be reflected phylogenetically by long terminal branches that may distinguish organisms from chronic and acute infections. Our work shows that selective pressures asserted by the hostile environment of the human gallbladder generate new antigenic variants and raises questions regarding the role of carriage in the epidemiology of typhoid fever.

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“…The strain BL196 was associated with a large outbreak in Kelantan, Malaysia in 2005 23 . Strains CR0044 and CR0063 were isolated from carrier individuals in 2007 after an outbreak and were reported to share PFGE profiles with the strain BL196 24 25 . Strain ST0208 was associated with a sporadic case in Kuala Lumpur, Malaysia 26 .…”

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confidence: 99%

Genome dynamics and evolution of Salmonella Typhi strains from the typhoid-endemic zones

Baddam

Kumar

Shaik

et al. 2014

Sci Rep

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Typhoid fever poses significant burden on healthcare systems in Southeast Asia and other endemic countries. Several epidemiological and genomic studies have attributed pseudogenisation to be the major driving force for the evolution of Salmonella Typhi although its real potential remains elusive. In the present study, we analyzed genomes of S. Typhi from different parts of Southeast Asia and Oceania, comprising of isolates from outbreak, sporadic and carrier cases. The genomes showed high genetic relatedness with limited opportunity for gene acquisition as evident from pan-genome structure. Given that pseudogenisation is an active process in S. Typhi, we further investigated core and pan-genome profiles of functional and pseudogenes separately. We observed a decline in core functional gene content and a significant increase in accessory pseudogene content. Upon functional classification, genes encoding metabolic functions formed a major constituent of pseudogenes as well as core functional gene clusters with SNPs. Further, an in-depth analysis of accessory pseudogene content revealed the existence of heterogeneous complements of functional and pseudogenes among the strains. In addition, these polymorphic genes were also enriched in metabolism related functions. Thus, the study highlights the existence of heterogeneous strains in a population with varying metabolic potential and that S. Typhi possibly resorts to metabolic fine tuning for its adaptation.

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Genome sequencing and analysis of Salmonella enterica serovar Typhi strain CR0063 representing a carrier individual during an outbreak of typhoid fever in Kelantan, Malaysia

Cited by 9 publications

References 60 publications

Salmonella Typhi genomics: envisaging the future of typhoid eradication

Salmonella Typhi genomics: envisaging the future of typhoid eradication

Gallbladder carriage generates genetic variation and genome degradation in Salmonella Typhi

Genome dynamics and evolution of Salmonella Typhi strains from the typhoid-endemic zones

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