Browsing by Author "Adegbola, R.A."
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Item Comparative phylogenomics of Streptococcus pneumoniae isolated from invasive disease and nasopharyngeal carriage from West Africans(2012-10-29) Donkor, E.S.; Stabler, R.A.; Hinds, J.; Adegbola, R.A.; Antonio, M.; Wren, B.WAbstract Background We applied comparative phylogenomics (whole genome comparisons of microbes using DNA microarrays combined with Bayesian-based phylogenies) to investigate S. pneumoniae isolates from West Africa, with the aim of providing insights into the pathogenicity and other features related to the biology of the organism. The strains investigated comprised a well defined collection of 58 invasive and carriage isolates that were sequenced typed and included eight different S. pneumoniae serotypes (1, 3, 5, 6A, 11, 14, 19 F and 23 F) of varying invasive disease potential. Results The core genome of the isolates was estimated to be 38% and was mainly represented by gene functional categories associated with housekeeping functions. Comparison of the gene content of invasive and carriage isolates identified at least eleven potential genes that may be important in virulence including surface proteins, transport proteins, transcription factors and hypothetical proteins. Thirteen accessory regions (ARs) were also identified and did not show any loci association with the eleven virulence genes. Intraclonal diversity (isolates of the same serotype and MLST but expressing different patterns of ARs) was observed among some clones including ST 1233 (serotype 5), ST 3404 (serotype 5) and ST 3321 (serotype 14). A constructed phylogenetic tree of the isolates showed a high level of heterogeneity consistent with the frequent S. pneumoniae recombination. Despite this, a homogeneous clustering of all the serotype 1 strains was observed. Conclusions Comparative phylogenomics of invasive and carriage S. pneumoniae isolates identified a number of putative virulence determinants that may be important in the progression of S. pneumoniae from the carriage phase to invasive disease. Virulence determinants that contribute to S. pneumoniae pathogenicity are likely to be distributed randomly throughout its genome rather than being clustered in dedicated loci or islands. Compared to other S. pneumoniae serotypes, serotype 1 appears most genetically uniform.Item Comparative phylogenomics of Streptococcus pneumoniae isolated from invasive disease and nasopharyngeal carriage from West Africans(2012-10-29) Donkor, E.S.; Stabler, R.A.; Hinds, J.; Adegbola, R.A.; Antonio, M.; Wren, B.W.Background: We applied comparative phylogenomics (whole genome comparisons of microbes using DNA microarrays combined with Bayesian-based phylogenies) to investigate S. pneumoniae isolates from West Africa, with the aim of providing insights into the pathogenicity and other features related to the biology of the organism. The strains investigated comprised a well defined collection of 58 invasive and carriage isolates that were sequenced typed and included eight different S. pneumoniae serotypes (1, 3, 5, 6A, 11, 14, 19 F and 23 F) of varying invasive disease potential.Results: The core genome of the isolates was estimated to be 38% and was mainly represented by gene functional categories associated with housekeeping functions. Comparison of the gene content of invasive and carriage isolates identified at least eleven potential genes that may be important in virulence including surface proteins, transport proteins, transcription factors and hypothetical proteins. Thirteen accessory regions (ARs) were also identified and did not show any loci association with the eleven virulence genes. Intraclonal diversity (isolates of the same serotype and MLST but expressing different patterns of ARs) was observed among some clones including ST 1233 (serotype 5), ST 3404 (serotype 5) and ST 3321 (serotype 14). A constructed phylogenetic tree of the isolates showed a high level of heterogeneity consistent with the frequent S. pneumoniae recombination. Despite this, a homogeneous clustering of all the serotype 1 strains was observed.Conclusions: Comparative phylogenomics of invasive and carriage S. pneumoniae isolates identified a number of putative virulence determinants that may be important in the progression of S. pneumoniae from the carriage phase to invasive disease. Virulence determinants that contribute to S. pneumoniae pathogenicity are likely to be distributed randomly throughout its genome rather than being clustered in dedicated loci or islands. Compared to other S. pneumoniae serotypes, serotype 1 appears most genetically uniform. © 2012 Donkor et al.; licensee BioMed Central Ltd.Item Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2.(2010-09) Thye, T.; Vannberg, F.O.; Wong, S.H.; Owusu-Dabo, E.; Osei, I.; Gyapong, J.; Sirugo, G.; Sisay-Joof, F.; Enimil, A.; Chinbuah, M.A.; Floyd, S.; Warndorff, D.K.; Sichali, L.; Malema, S.; Crampin, A.C.; Ngwira, B.; Teo, Y.Y.; Small, K.; Rockett, K.; Kwiatkowski, D.; Fine, P.E.; Hill, P.C.; Newport, M.; Lienhardt, C.; Adegbola, R.A.; Corrah, T.; Ziegler, A.; African TB Genetics Consortium; Wellcome Trust Case Control Consortium; Morris, A.P.; Meyer, C.G.; Horstmann, R.D.; Hill, A.V.We combined two tuberculosis genome-wide association studies from Ghana and The Gambia with subsequent replication in a combined 11,425 individuals. rs4331426, located in a gene-poor region on chromosome 18q11.2, was associated with disease (combined P = 6.8 x 10(-9), odds ratio = 1.19, 95% CI = 1.13-1.27). Our study demonstrates that genome-wide association studies can identify new susceptibility loci for infectious diseases, even in African populations, in which levels of linkage disequilibrium are particularly low.Item Population Biology of Streptococcus pneumonia in West Africa: Multi-locus Sequence Typing of Stereotypes That Exhibit Different Predisposition to Invasive Disease and Carriage(Public Library of Science, 2013) Donkor, E.S.; Adegbola, R.A.; Wren, B.W.; Antonio, M.Background: Little is known about the population biology of Streptococcus pneumonia in developing countries, although the majority of pneumococcal infections occur in this setting. The aim of the study was to apply MLST to investigate the population biology of S. pneumonia in West Africa. Methods: Seventy three invasive and carriage S. pneumonia isolates from three West African countries including The Gambia, Nigeria and Ghana were investigated. The isolates covered seven stereotypes (1, 3, 5, 6A, 11, 14, 23F) and were subjected to multi-locus sequence typing and antibiotic susceptibility testing. Results: Overall, 50 different sequence types (STs) were identified, of which 38% (29) were novel. The most common ST was a novel clone-ST 4012 (6.5%), and some clones including STs 913, 925, 1737, 2160 and 3310 appeared to be specific to the study region. Two STs including ST 63 and ST 4012 were associated with multiple stereotypes indicating a history of stereotype switching. ST 63 was associated with stereotypes 3 and 23F, while ST 4012 was associated with stereotypes 6A and 23. eBURST analyses using the stringent 6/7 identical loci definition grouped the 50 STs into 5 clonal complexes and 65 singletons, expressing a high level of genetic diversity among the isolates. Compared to the other stereotypes, stereotypes 1 and 5 isolates appeared to be more clonal. Internationally recognized antibiotic resistant clones of S. pneumonia were generally absent in the population investigated and the only multi-drug resistant isolate identified (1/66) belong to the Pneumococcal Epidemiology Network clone ST 63. Conclusions: The pneumococcal population in West Africa is quite divergent, and stereotypes that are common in invasive disease (such as stereotypes 1 and 5) are more likely to be clonal than stereotypes that are common in carriage.Item Population Biology of Streptococcus pneumoniae in West Africa: Multilocus Sequence Typing of Serotypes That Exhibit Different Predisposition to Invasive Disease and Carriage(2013-01-16) Donkor, E.S.; Adegbola, R.A.; Wren, B.W.; Antonio, M.Background: Little is known about the population biology of Streptococcus pneumoniae in developing countries, although the majority of pneumococcal infections occur in this setting. The aim of the study was to apply MLST to investigate the population biology of S. pneumoniae in West Africa. Methods: Seventy three invasive and carriage S. pneumoniae isolates from three West African countries including The Gambia, Nigeria and Ghana were investigated. The isolates covered seven serotypes (1, 3, 5, 6A, 11, 14, 23F) and were subjected to multilocus sequence typing and antibiotic susceptibility testing. Results: Overall, 50 different sequence types (STs) were identified, of which 38% (29) were novel. The most common ST was a novel clone-ST 4012 (6.5%), and some clones including STs 913, 925, 1737, 2160 and 3310 appeared to be specific to the study region. Two STs including ST 63 and ST 4012 were associated with multiple serotypes indicating a history of serotype switching. ST 63 was associated with serotypes 3 and 23F, while ST 4012 was associated with serotypes 6A and 23. eBURST analyses using the stringent 6/7 identical loci definition grouped the 50 STs into 5 clonal complexes and 65 singletons, expressing a high level of genetic diversity among the isolates. Compared to the other serotypes, serotypes 1 and 5 isolates appeared to be more clonal. Internationally recognized antibiotic resistant clones of S. pneumoniae were generally absent in the population investigated and the only multidrug resistant isolate identified (1/66) belong to the Pneumocococcal Epidemiology Network clone ST 63. Conclusions: The pneumococcal population in West Africa is quite divergent, and serotypes that are common in invasive disease (such as serotypes 1 and 5) are more likely to be clonal than serotypes that are common in carriage. © 2013 Donkor et al.Item Population Biology of Streptococcus pneumoniae in West Africa: Multilocus Sequence Typing of Serotypes That Exhibit Different Predisposition to Invasive Disease and Carriage(PLOS ONE, 2013) Donkor, E.S.; Adegbola, R.A.; Wren, B.W.; Antonio, M.Background: Little is known about the population biology of Streptococcus pneumoniae in developing countries, although the majority of pneumococcal infections occur in this setting. The aim of the study was to apply MLST to investigate the population biology of S. pneumoniae in West Africa. Methods: Seventy three invasive and carriage S. pneumoniae isolates from three West African countries including The Gambia, Nigeria and Ghana were investigated. The isolates covered seven serotypes (1, 3, 5, 6A, 11, 14, 23F) and were subjected to multilocus sequence typing and antibiotic susceptibility testing. Results: Overall, 50 different sequence types (STs) were identified, of which 38% (29) were novel. The most common ST was a novel clone-ST 4012 (6.5%), and some clones including STs 913, 925, 1737, 2160 and 3310 appeared to be specific to the study region. Two STs including ST 63 and ST 4012 were associated with multiple serotypes indicating a history of serotype switching. ST 63 was associated with serotypes 3 and 23F, while ST 4012 was associated with serotypes 6A and 23. eBURST analyses using the stringent 6/7 identical loci definition grouped the 50 STs into 5 clonal complexes and 65 singletons, expressing a high level of genetic diversity among the isolates. Compared to the other serotypes, serotypes 1 and 5 isolates appeared to be more clonal. Internationally recognized antibiotic resistant clones of S. pneumoniae were generally absent in the population investigated and the only multidrug resistant isolate identified (1/66) belong to the Pneumocococcal Epidemiology Network clone ST 63. Conclusions: The pneumococcal population in West Africa is quite divergent, and serotypes that are common in invasive disease (such as serotypes 1 and 5) are more likely to be clonal than serotypes that are common in carriage.