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2.
Nat Genet ; 38(7): 779-86, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16804543

RESUMO

We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism.


Assuntos
Clostridioides difficile/genética , Clostridioides difficile/patogenicidade , Adaptação Fisiológica , Proteínas de Bactérias/genética , Sequência de Bases , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/fisiologia , Conjugação Genética , Elementos de DNA Transponíveis/genética , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla/genética , Enterocolite Pseudomembranosa/etiologia , Enterocolite Pseudomembranosa/microbiologia , Trato Gastrointestinal/microbiologia , Genoma Bacteriano , Humanos , Dados de Sequência Molecular , Mosaicismo , Análise de Sequência com Séries de Oligonucleotídeos , Esporos Bacterianos/fisiologia , Virulência/genética
3.
Proc Natl Acad Sci U S A ; 101(26): 9786-91, 2004 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-15213324

RESUMO

Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the approximately 2.8-Mbp genomes of two disease-causing S. aureus strains isolated from distinct clinical settings: a recent hospital-acquired representative of the epidemic methicillin-resistant S. aureus EMRSA-16 clone (MRSA252), a clinically important and globally prevalent lineage; and a representative of an invasive community-acquired methicillin-susceptible S. aureus clone (MSSA476). A comparative-genomics approach was used to explore the mechanisms of evolution of clinically important S. aureus genomes and to identify regions affecting virulence and drug resistance. The genome sequences of MRSA252 and MSSA476 have a well conserved core region but differ markedly in their accessory genetic elements. MRSA252 is the most genetically diverse S. aureus strain sequenced to date: approximately 6% of the genome is novel compared with other published genomes, and it contains several unique genetic elements. MSSA476 is methicillin-susceptible, but it contains a novel Staphylococcal chromosomal cassette (SCC) mec-like element (designated SCC(476)), which is integrated at the same site on the chromosome as SCCmec elements in MRSA strains but encodes a putative fusidic acid resistance protein. The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA community-acquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.


Assuntos
Farmacorresistência Bacteriana/genética , Evolução Molecular , Genoma Bacteriano , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Farmacorresistência Bacteriana/efeitos dos fármacos , Genes Bacterianos/genética , Variação Genética , Genômica , Humanos , Filogenia , Análise de Sequência de DNA , Staphylococcus aureus/classificação , Staphylococcus aureus/efeitos dos fármacos , Virulência/genética
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