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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 06 May 2014, Vol.111(18), pp.6738-43
    Description: During the last 2 decades, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have dramatically increased the global burden of S. aureus infections. The pandemic sequence type (ST)8/pulsed-field gel type USA300 is the dominant CA-MRSA clone in the United States, but its evolutionary history and basis for biological success are incompletely understood. Here, we use whole-genome sequencing of 387 ST8 isolates drawn from an epidemiological network of CA-MRSA infections and colonizations in northern Manhattan to explore short-term evolution and transmission patterns. Phylogenetic analysis predicted that USA300 diverged from a most common recent ancestor around 1993. We found evidence for multiple introductions of USA300 and reconstructed the phylogeographic spread of isolates across neighborhoods. Using pair-wise single-nucleotide polymorphism distances as a measure of genetic relatedness between isolates, we observed that most USA300 isolates had become endemic in households, indicating their critical role as reservoirs for transmission and diversification. Using the maximum single-nucleotide polymorphism variability of isolates from within households as a threshold, we identified several possible transmission networks beyond households. Our study also revealed the evolution of a fluoroquinolone-resistant subpopulation in the mid-1990s and its subsequent expansion at a time of high-frequency outpatient antibiotic use. This high-resolution phylogenetic analysis of ST8 has documented the genomic changes associated with USA300 evolution and how some of its recent evolution has been shaped by antibiotic use. By integrating whole-genome sequencing with detailed epidemiological analyses, our study provides an important framework for delineating the full diversity and spread of USA300 and other emerging pathogens in large urban community populations.
    Keywords: Cc8 ; Drug Resistance ; Genomics ; Phylogeny ; Methicillin-Resistant Staphylococcus Aureus -- Genetics ; Staphylococcal Infections -- Epidemiology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    In: Nature, 2003, Vol.423(6935), p.23
    Keywords: Genome, Bacterial ; Phylogeny ; Bacillus Anthracis -- Classification ; Bacillus Cereus -- Classification ; Genes, Bacterial -- Genetics;
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 3
    In: Nature, 2002, Vol.417(6887), p.379
    Keywords: Bacteria–Genetics ; Bacteria–Pathogenicity ; Bioterrorism–Prevention & Control ; Genome–Legislation & Jurisprudence ; Genomics–Legislation & Jurisprudence ; Humans–Legislation & Jurisprudence ; Public Sector–Legislation & Jurisprudence ; Publishing–Legislation & Jurisprudence ; Security Measures–Legislation & Jurisprudence;
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 4
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 16 July 2013, Vol.110(29), pp.11923-7
    Description: Genome-wide association studies have the potential to identify causal genetic factors underlying important phenotypes but have rarely been performed in bacteria. We present an association mapping method that takes into account the clonal population structure of bacteria and is applicable to both core and accessory genome variation. Campylobacter is a common cause of human gastroenteritis as a consequence of its proliferation in multiple farm animal species and its transmission via contaminated meat and poultry. We applied our association mapping method to identify the factors responsible for adaptation to cattle and chickens among 192 Campylobacter isolates from these and other host sources. Phylogenetic analysis implied frequent host switching but also showed that some lineages were strongly associated with particular hosts. A seven-gene region with a host association signal was found. Genes in this region were almost universally present in cattle but were frequently absent in isolates from chickens and wild birds. Three of the seven genes encoded vitamin B5 biosynthesis. We found that isolates from cattle were better able to grow in vitamin B5-depleted media and propose that this difference may be an adaptation to host diet.
    Keywords: Evolution ; Genomics ; Host Adaptation ; Transmission Ecology ; Biological Evolution ; Biosynthetic Pathways -- Genetics ; Campylobacter -- Genetics ; Cattle -- Microbiology ; Genome-Wide Association Study -- Methods ; Host Specificity -- Genetics ; Pantothenic Acid -- Biosynthesis
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 5
    Language: English
    In: Proceedings. Biological sciences, 22 December 2015, Vol.282(1821), pp.20150488
    Description: Since the first complete sequencing of a free-living organism, Haemophilus influenzae, genomics has been used to probe both the biology of bacterial pathogens and their evolution. Single-genome approaches provided information on the repertoire of virulence determinants and host-interaction factors, and, along with comparative analyses, allowed the proposal of hypotheses to explain the evolution of many of these traits. These analyses suggested many bacterial pathogens to be of relatively recent origin and identified genome degradation as a key aspect of host adaptation. The advent of very-high-throughput sequencing has allowed for detailed phylogenetic analysis of many important pathogens, revealing patterns of global and local spread, and recent evolution in response to pressure from therapeutics and the human immune system. Such analyses have shown that bacteria can evolve and transmit very rapidly, with emerging clones showing adaptation and global spread over years or decades. The resolution achieved with whole-genome sequencing has shown considerable benefits in clinical microbiology, enabling accurate outbreak tracking within hospitals and across continents. Continued large-scale sequencing promises many further insights into genetic determinants of drug resistance, virulence and transmission in bacterial pathogens.
    Keywords: Bacterial Evolution ; Bacterial Genomics ; Bacterial Transmission ; Evolution, Molecular ; Genome, Bacterial ; Bacteria -- Genetics ; Bacterial Infections -- Microbiology
    ISSN: 09628452
    E-ISSN: 1471-2954
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  • 6
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 11 August 2015, Vol.112(32), pp.10008-13
    Description: Multidrug resistance, strong side effects, and compliance problems in TB chemotherapy mandate new ways to kill Mycobacterium tuberculosis (Mtb). Here we show that deletion of the gene encoding homoserine transacetylase (metA) inactivates methionine and S-adenosylmethionine (SAM) biosynthesis in Mtb and renders this pathogen exquisitely sensitive to killing in immunocompetent or immunocompromised mice, leading to rapid clearance from host tissues. Mtb ΔmetA is unable to proliferate in primary human macrophages, and in vitro starvation leads to extraordinarily rapid killing with no appearance of suppressor mutants. Cell death of Mtb ΔmetA is faster than that of other auxotrophic mutants (i.e., tryptophan, pantothenate, leucine, biotin), suggesting a particularly potent mechanism of killing. Time-course metabolomics showed complete depletion of intracellular methionine and SAM. SAM depletion was consistent with a significant decrease in methylation at the DNA level (measured by single-molecule real-time sequencing) and with the induction of several essential methyltransferases involved in biotin and menaquinone biosynthesis, both of which are vital biological processes and validated targets of antimycobacterial drugs. Mtb ΔmetA could be partially rescued by biotin supplementation, confirming a multitarget cell death mechanism. The work presented here uncovers a previously unidentified vulnerability of Mtb-the incapacity to scavenge intermediates of SAM and methionine biosynthesis from the host. This vulnerability unveils an entirely new drug target space with the promise of rapid killing of the tubercle bacillus by a new mechanism of action.
    Keywords: Amino Acid Biosynthesis ; Bactericidal Auxotrophy ; Host–Pathogen Interaction ; Metabolism ; Methionine -- Pharmacology ; Mycobacterium Tuberculosis -- Drug Effects ; S-Adenosylmethionine -- Pharmacology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 7
    In: Nature Reviews Microbiology, 2013, Vol.11(10), p.664
    Description: This month's Genome Watch looks back over the past 10 years and highlights how the incredible advances in sequencing technologies have transformed research into microbial genomes.
    Keywords: Bacillus Anthracis–Genetics ; Bordetella–Genetics ; Genetic Variation–Genetics ; Genome, Bacterial–Genetics ; Genomics–Genetics ; High-Throughput Nucleotide Sequencing–Genetics ; Humans–Genetics ; Metagenome–Genetics ; Porphyromonas Gingivalis–Genetics ; Uropathogenic Escherichia Coli–Genetics;
    ISSN: 1740-1526
    E-ISSN: 17401534
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  • 8
    Language: English
    In: JAPANESE JOURNAL OF BACTERIOLOGY, 2011, Vol.66(3), pp.294-294
    Keywords: Biology;
    ISSN: 0021-4930
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  • 9
    Language: English
    In: Science (New York, N.Y.), 28 January 2011, Vol.331(6016), pp.430-4
    Description: Epidemiological studies of the naturally transformable bacterial pathogen Streptococcus pneumoniae have previously been confounded by high rates of recombination. Sequencing 240 isolates of the PMEN1 (Spain(23F)-1) multidrug-resistant lineage enabled base substitutions to be distinguished from polymorphisms arising through horizontal sequence transfer. More than 700 recombinations were detected, with genes encoding major antigens frequently affected. Among these were 10 capsule-switching events, one of which accompanied a population shift as vaccine-escape serotype 19A isolates emerged in the USA after the introduction of the conjugate polysaccharide vaccine. The evolution of resistance to fluoroquinolones, rifampicin, and macrolides was observed to occur on multiple occasions. This study details how genomic plasticity within lineages of recombinogenic bacteria can permit adaptation to clinical interventions over remarkably short time scales.
    Keywords: Evolution, Molecular ; Recombination, Genetic ; Pneumococcal Infections -- Microbiology ; Streptococcus Pneumoniae -- Genetics
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 10
    Article
    Article
    In: Nature Biotechnology, 2000, Vol.18(5), p.493
    Description: The relatively young field of genome sequencing is split by a debate between those who believe that the sequence produced must be as complete and accurate as technically possible in order to generate the greatest amount of useful data, and those who believe that a partial or survey sequence is sufficient for most purposes. At stake is the large investment in extra money and manpower required to progress from a partial shotgun, which can be generated rapidly and relatively cheaply, to a complete and accurate sequence ("banging in every last base" in one memorable phrase). In a recent paper in PNAS, Selkov and colleagues add their contribution to this debate. They describe the production of a partial ("gapped") genome sequence of the biomining organism Thiobacillus ferrooxidans and the analysis of the sequence using a dedicated software suite to reconstruct parts of the central metabolism of this organism.
    Keywords: Thiobacillus Ferrooxidans ; Thiobacillus Ferrooxidans ; Thiobacillus Ferrooxidans ; Computer Applications ; Genomes ; Reviews ; Computer Applications ; Genomes ; Reviews ; Computer Applications ; Genomes ; Reviews ; General Topics and Reviews ; Genetics and Evolution ; Bacterial Genetics ; Miscellaneous, Reviews;
    ISSN: 1087-0156
    E-ISSN: 1546-1696
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