- Volume 1, Issue 2, 2015
Volume 1, Issue 2, 2015
- Research Paper
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- Microbial evolution and epidemiology
- Phylogeography
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Region-specific diversification of the highly virulent serotype 1 Streptococcus pneumoniae
Jennifer E. Cornick, Chrispin Chaguza, Simon R. Harris, Feyruz Yalcin, Madikay Senghore, Anmol M. Kiran, Shanil Govindpershad, Sani Ousmane, Mignon Du Plessis, Gerd Pluschke, Chinelo Ebruke, Lesley McGee, Beutel Sigaùque, Jean-Marc Collard, Martin Antonio, Anne von Gottberg, Neil French, Keith P. Klugman, Robert S. Heyderman, Stephen D. Bentley, Dean B. Everett and for the PAGe ConsortiumSerotype 1 Streptococcus pneumoniae is a leading cause of invasive pneumococcal disease (IPD) worldwide, with the highest burden in developing countries. We report the whole-genome sequencing analysis of 448 serotype 1 isolates from 27 countries worldwide (including 11 in Africa). The global serotype 1 population shows a strong phylogeographic structure at the continental level, and within Africa there is further region-specific structure. Our results demonstrate that region-specific diversification within Africa has been driven by limited cross-region transfer events, genetic recombination and antimicrobial selective pressure. Clonal replacement of the dominant serotype 1 clones circulating within regions is uncommon; however, here we report on the accessory gene content that has contributed to a rare clonal replacement event of ST3081 with ST618 as the dominant cause of IPD in the Gambia.
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- Responses to human interventions
- Antibiotics
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Large tandem chromosome expansions facilitate niche adaptation during persistent infection with drug-resistant Staphylococcus aureus
We used genomics to study the evolution of meticillin-resistant Staphylococcus aureus (MRSA) during a complex, protracted clinical infection. Preparing closed MRSA genomes from days 0 and 115 allowed us to precisely reconstruct all genetic changes that occurred. Twenty-three MRSA blood cultures were also obtained during treatment, yielding 44 colony morphotypes that varied in size, haemolysis and antibiotic susceptibility. A subset of 15 isolates was sequenced and shown to harbour a total of 37 sequence polymorphisms. Eighty per cent of all mutations occurred from day 45 onwards, which coincided with the appearance of discrete chromosome expansions, and concluded in the day 115 isolate with a 98 kb tandem DNA duplication. In all heterogeneous vancomycin-intermediate Staphylococcus aureus isolates, the chromosomal amplification spanned at least a 20 kb region that notably included mprF, a gene involved in resistance to antimicrobial peptides, and parC, an essential DNA replication gene with an unusual V463 codon insertion. Restoration of the chromosome after serial passage under non-selective growth was accompanied by increased susceptibility to antimicrobial peptide killing and reduced vancomycin resistance, two signature phenotypes that help explain the clinical persistence of this strain. Elevated expression of the V463 parC was deleterious to the cell and reduced colony size, but did not alter ciprofloxacin susceptibility. In this study, we identified large DNA expansions as a clinically relevant mechanism of S. aureus resistance and persistence, demonstrating the extent to which bacterial chromosomes remodel in the face of antibiotic and host immune pressures.
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- Methods Paper
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- Systems Microbiology
- Large-scale comparative genomics
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Redefining the differences in gene content between Yersinia pestis and Yersinia pseudotuberculosis using large-scale comparative genomics
More LessYersinia pestis, the causative agent of plague, is best known for historical pandemics, but still actively causes disease in many parts of the world. Y. pestis is a recently derived clone of the pathogenic species Yersinia pseudotuberculosis, but is more associated with human infection. Numerous studies have documented genomic changes since the two species differentiated, although all of these studies used a relatively small sample set for defining these differences. In this study, we compared the complete genomic content between a diverse set of Y. pestis and Y. pseudotuberculosis genomes, and identified unique loci that could serve as diagnostic markers or for better understanding the evolution and pathogenesis of each group. Comparative genomics analyses also identified subtle variations in gene content between individual monophyletic clades within these species, based on a core genome single nucleotide polymorphism phylogeny that would have been undetected in a less comprehensive genome dataset. We also screened loci that were identified in other published studies as unique to either species and generally found a non-uniform distribution, suggesting that the assignment of these unique genes to either species should be re-evaluated in the context of current sequencing efforts. Overall, this study provides a high-resolution view into the genomic differences between Y. pestis and Y. pseudotuberculosis, demonstrating fine-scale differentiation and unique gene composition in both species.
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