Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella

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Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella. / Hammarlöf, Disa L; Kröger, Carsten; Owen, Siân V; Canals, Rocío; Lacharme-Lora, Lizeth; Wenner, Nicolas; Schager, Anna E; Wells, Timothy J; Henderson, Ian R; Wigley, Paul; Hokamp, Karsten; Feasey, Nicholas A; Gordon, Melita A; Hinton, Jay C D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 11, 13.03.2018, p. E2614-E2623.

Research output: Contribution to journalArticle

Harvard

Hammarlöf, DL, Kröger, C, Owen, SV, Canals, R, Lacharme-Lora, L, Wenner, N, Schager, AE, Wells, TJ, Henderson, IR, Wigley, P, Hokamp, K, Feasey, NA, Gordon, MA & Hinton, JCD 2018, 'Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella', Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 11, pp. E2614-E2623. https://doi.org/10.1073/pnas.1714718115

APA

Hammarlöf, D. L., Kröger, C., Owen, S. V., Canals, R., Lacharme-Lora, L., Wenner, N., Schager, A. E., Wells, T. J., Henderson, I. R., Wigley, P., Hokamp, K., Feasey, N. A., Gordon, M. A., & Hinton, J. C. D. (2018). Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella. Proceedings of the National Academy of Sciences of the United States of America, 115(11), E2614-E2623. https://doi.org/10.1073/pnas.1714718115

Vancouver

Author

Hammarlöf, Disa L ; Kröger, Carsten ; Owen, Siân V ; Canals, Rocío ; Lacharme-Lora, Lizeth ; Wenner, Nicolas ; Schager, Anna E ; Wells, Timothy J ; Henderson, Ian R ; Wigley, Paul ; Hokamp, Karsten ; Feasey, Nicholas A ; Gordon, Melita A ; Hinton, Jay C D. / Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 11. pp. E2614-E2623.

Bibtex

@article{9f4d105f10d5482491378e16a81e2ac1,
title = "Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella",
abstract = "Salmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely related to the ST19 group of S Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by only ∼1,000 SNPs. We hypothesized that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites of the ST313 strain D23580, and searched for a gene-expression signature linked to pathogenesis of Salmonella We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance, and modulated virulence in the chicken infection model. We propose that high levels of PgtE expression by African S Typhimurium ST313 promote bacterial survival and dissemination during human infection. Our finding of a functional role for an extragenic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on noncoding regions of the genome.",
keywords = "Salmonella, noncoding genome, transcriptomics, evolution of virulence, host adaptation",
author = "Hammarl{\"o}f, {Disa L} and Carsten Kr{\"o}ger and Owen, {Si{\^a}n V} and Roc{\'i}o Canals and Lizeth Lacharme-Lora and Nicolas Wenner and Schager, {Anna E} and Wells, {Timothy J} and Henderson, {Ian R} and Paul Wigley and Karsten Hokamp and Feasey, {Nicholas A} and Gordon, {Melita A} and Hinton, {Jay C D}",
note = "Copyright {\textcopyright} 2018 the Author(s). Published by PNAS.",
year = "2018",
month = mar,
day = "13",
doi = "10.1073/pnas.1714718115",
language = "English",
volume = "115",
pages = "E2614--E2623",
journal = "National Academy of Sciences. Proceedings",
issn = "1091-6490",
publisher = "National Academy of Sciences",
number = "11",

}

RIS

TY - JOUR

T1 - Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella

AU - Hammarlöf, Disa L

AU - Kröger, Carsten

AU - Owen, Siân V

AU - Canals, Rocío

AU - Lacharme-Lora, Lizeth

AU - Wenner, Nicolas

AU - Schager, Anna E

AU - Wells, Timothy J

AU - Henderson, Ian R

AU - Wigley, Paul

AU - Hokamp, Karsten

AU - Feasey, Nicholas A

AU - Gordon, Melita A

AU - Hinton, Jay C D

N1 - Copyright © 2018 the Author(s). Published by PNAS.

PY - 2018/3/13

Y1 - 2018/3/13

N2 - Salmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely related to the ST19 group of S Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by only ∼1,000 SNPs. We hypothesized that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites of the ST313 strain D23580, and searched for a gene-expression signature linked to pathogenesis of Salmonella We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance, and modulated virulence in the chicken infection model. We propose that high levels of PgtE expression by African S Typhimurium ST313 promote bacterial survival and dissemination during human infection. Our finding of a functional role for an extragenic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on noncoding regions of the genome.

AB - Salmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely related to the ST19 group of S Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by only ∼1,000 SNPs. We hypothesized that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites of the ST313 strain D23580, and searched for a gene-expression signature linked to pathogenesis of Salmonella We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance, and modulated virulence in the chicken infection model. We propose that high levels of PgtE expression by African S Typhimurium ST313 promote bacterial survival and dissemination during human infection. Our finding of a functional role for an extragenic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on noncoding regions of the genome.

KW - Salmonella

KW - noncoding genome

KW - transcriptomics

KW - evolution of virulence

KW - host adaptation

U2 - 10.1073/pnas.1714718115

DO - 10.1073/pnas.1714718115

M3 - Article

C2 - 29487214

VL - 115

SP - E2614-E2623

JO - National Academy of Sciences. Proceedings

JF - National Academy of Sciences. Proceedings

SN - 1091-6490

IS - 11

ER -