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Comparative genomics of closely related Salmonella enterica serovar Typhi strains reveals genome dynamics and the acquisition of novel pathogenic elements

Yap, Kien-Pong, Gan, Han Ming, Teh, Cindy Shuan Ju, Chai, Lay Ching and Thong, Kwai Lin 2014, Comparative genomics of closely related Salmonella enterica serovar Typhi strains reveals genome dynamics and the acquisition of novel pathogenic elements, BMC genomics, vol. 15, pp. 1-20, doi: 10.1186/1471-2164-15-1007.

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Title Comparative genomics of closely related Salmonella enterica serovar Typhi strains reveals genome dynamics and the acquisition of novel pathogenic elements
Formatted title Comparative genomics of closely related Salmonella enterica serovar Typhi strains reveals genome dynamics and the acquisition of novel pathogenic elements
Author(s) Yap, Kien-Pong
Gan, Han MingORCID iD for Gan, Han Ming orcid.org/0000-0001-7987-738X
Teh, Cindy Shuan Ju
Chai, Lay Ching
Thong, Kwai Lin
Journal name BMC genomics
Volume number 15
Article ID 1007
Start page 1
End page 20
Total pages 20
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2014
ISSN 1471-2164
Keyword(s) bacterial proteins
carrier state
clustered regularly interspaced short palindromic repeats
disease outbreaks
evolution, molecular
gene order
genome, bacterial
genomic islands
genomics
models, molecular
mutagenesis, insertional
phylogeny
polymorphism, single nucleotide
protein conformation
salmonella phages
salmonella typhi
typhoid fever
virulence factors
S. Typhi
typhoid
genomes
comparative genomics
pathogen
zot
SPI
T6SS
phylogenetic
Enterobacteriaceae
sequence
evolution
protein
strain
variation
virulence
infection
protein modelling
Summary BACKGROUND: Typhoid fever is an infectious disease of global importance that is caused by Salmonella enterica subsp. enterica serovar Typhi (S. Typhi). This disease causes an estimated 200,000 deaths per year and remains a serious global health threat. S. Typhi is strictly a human pathogen, and some recovered individuals become long-term carriers who continue to shed the bacteria in their faeces, thus becoming main reservoirs of infection.

RESULTS: A comparative genomics analysis combined with a phylogenomic analysis revealed that the strains from the outbreak and carrier were closely related with microvariations and possibly derived from a common ancestor. Additionally, the comparative genomics analysis with all of the other completely sequenced S. Typhi genomes revealed that strains BL196 and CR0044 exhibit unusual genomic variations despite S. Typhi being generally regarded as highly clonal. The two genomes shared distinct chromosomal architectures and uncommon genome features; notably, the presence of a ~10 kb novel genomic island containing uncharacterised virulence-related genes, and zot in particular. Variations were also detected in the T6SS system and genes that were related to SPI-10, insertion sequences, CRISPRs and nsSNPs among the studied genomes. Interestingly, the carrier strain CR0044 harboured far more genetic polymorphisms (83% mutant nsSNPs) compared with the closely related BL196 outbreak strain. Notably, the two highly related virulence-determinant genes, rpoS and tviE, were mutated in strains BL196 and CR0044, respectively, which revealed that the mutation in rpoS is stabilising, while that in tviE is destabilising. These microvariations provide novel insight into the optimisation of genes by the pathogens. However, the sporadic strain was found to be far more conserved compared with the others.

CONCLUSIONS: The uncommon genomic variations in the two closely related BL196 and CR0044 strains suggests that S. Typhi is more diverse than previously thought. Our study has demonstrated that the pathogen is continually acquiring new genes through horizontal gene transfer in the process of host adaptation, providing novel insight into its unusual genomic dynamics. The understanding of these strains and virulence factors, and particularly the strain that is associated with the large outbreak and the less studied asymptomatic Typhi carrier in the population, will have important impact on disease control.
Language eng
DOI 10.1186/1471-2164-15-1007
Field of Research 060408 Genomics
060503 Microbial Genetics
110801 Medical Bacteriology
06 Biological Sciences
11 Medical And Health Sciences
08 Information And Computing Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, Yap et al
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30101906

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.