Biochemistry and Pharmacology - Research Publications

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Author: Dougan, Gordon × Author: Holt, Kathryn × End date: 2012 × Start date: 2012 ×

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    Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe
    Holt, KE ; Baker, S ; Weill, F-X ; Holmes, EC ; Kitchen, A ; Yu, J ; Sangal, V ; Brown, DJ ; Coia, JE ; Kim, DW ; Choi, SY ; Kim, SH ; da Silveira, WD ; Pickard, DJ ; Farrar, JJ ; Parkhill, J ; Dougan, G ; Thomson, NR (NATURE PORTFOLIO, 2012-09)
    Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery(1,2), spreading efficiently via low-dose fecal-oral transmission(3,4). Historically, S. sonnei has been predominantly responsible for dysentery in developed countries but is now emerging as a problem in the developing world, seeming to replace the more diverse Shigella flexneri in areas undergoing economic development and improvements in water quality(4-6). Classical approaches have shown that S. sonnei is genetically conserved and clonal(7). We report here whole-genome sequencing of 132 globally distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and that diversified into several distinct lineages with unique characteristics. Our analysis suggests that the majority of this diversification occurred in Europe and was followed by more recent establishment of local pathogen populations on other continents, predominantly due to the pandemic spread of a single, rapidly evolving, multidrug-resistant lineage.
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    High-Resolution Genotyping of the Endemic Salmonella Typhi Population during a Vi (Typhoid) Vaccination Trial in Kolkata
    Holt, KE ; Dutta, S ; Manna, B ; Bhattacharya, SK ; Bhaduri, B ; Pickard, DJ ; Ochiai, RL ; Ali, M ; Clemens, JD ; Dougan, G ; Vinetz, JM (PUBLIC LIBRARY SCIENCE, 2012-01)
    BACKGROUND: Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem especially in developing countries. Vaccines against typhoid are commonly used by travelers but less so by residents of endemic areas. METHODOLOGY: We used single nucleotide polymorphism (SNP) typing to investigate the population structure of 372 S. Typhi isolated during a typhoid disease burden study and Vi vaccine trial in Kolkata, India. Approximately sixty thousand people were enrolled for fever surveillance for 19 months prior to, and 24 months following, Vi vaccination of one third of the study population (May 2003-December 2006, vaccinations given December 2004). PRINCIPAL FINDINGS: A diverse S. Typhi population was detected, including 21 haplotypes. The most common were of the H58 haplogroup (69%), which included all multidrug resistant isolates (defined as resistance to chloramphenicol, ampicillin and co-trimoxazole). Quinolone resistance was particularly high among H58-G isolates (97% Nalidixic acid resistant, 30% with reduced susceptibility to ciprofloxacin). Multiple typhoid fever episodes were detected in 22 households, however household clustering was not associated with specific S. Typhi haplotypes. CONCLUSIONS: Typhoid fever in Kolkata is caused by a diverse population of S. Typhi, however H58 haplotypes dominate and are associated with multidrug and quinolone resistance. Vi vaccination did not obviously impact on the haplotype population structure of the S. Typhi circulating during the study period.