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1.
J Infect Dis ; 207(6): 919-28, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23288927

RESUMO

BACKGROUND: Fluoroquinolone-resistant Escherichia coli are increasingly prevalent. Their clonal origins--potentially critical for control efforts--remain undefined. METHODS: Antimicrobial resistance profiles and fine clonal structure were determined for 236 diverse-source historical (1967-2009) E. coli isolates representing sequence type ST131 and 853 recent (2010-2011) consecutive E. coli isolates from 5 clinical laboratories in Seattle, Washington, and Minneapolis, Minnesota. Clonal structure was resolved based on fimH sequence (fimbrial adhesin gene: H subclone assignments), multilocus sequence typing, gyrA and parC sequence (fluoroquinolone resistance-determining loci), and pulsed-field gel electrophoresis. RESULTS: Of the recent fluoroquinolone-resistant clinical isolates, 52% represented a single ST131 subclonal lineage, H30, which expanded abruptly after 2000. This subclone had a unique and conserved gyrA/parC allele combination, supporting its tight clonality. Unlike other ST131 subclones, H30 was significantly associated with fluoroquinolone resistance and was the most prevalent subclone among current E. coli clinical isolates, overall (10.4%) and within every resistance category (11%-52%). CONCLUSIONS: Most current fluoroquinolone-resistant E. coli clinical isolates, and the largest share of multidrug-resistant isolates, represent a highly clonal subgroup that likely originated from a single rapidly expanded and disseminated ST131 strain. Focused attention to this strain will be required to control the fluoroquinolone and multidrug-resistant E. coli epidemic.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Escherichia coli/microbiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Fluoroquinolonas/farmacologia , Adesinas de Escherichia coli/genética , Evolução Clonal , DNA Girase/genética , DNA Topoisomerase IV/genética , DNA Bacteriano/genética , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Proteínas de Fímbrias/genética , Humanos , Epidemiologia Molecular , Tipagem de Sequências Multilocus
2.
J Clin Microbiol ; 51(9): 2991-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23843485

RESUMO

The ability to identify bacterial pathogens at the subspecies level in clinical diagnostics is currently limited. We investigated whether splitting Escherichia coli species into clonal groups (clonotypes) predicts antimicrobial susceptibility or clinical outcome. A total of 1,679 extraintestinal E. coli isolates (collected from 2010 to 2012) were collected from one German and 5 U.S. clinical microbiology laboratories. Clonotype identity was determined by fumC and fimH (CH) sequencing. The associations of clonotype with antimicrobial susceptibility and clinical variables were evaluated. CH typing divided the isolates into >200 CH clonotypes, with 93% of the isolates belonging to clonotypes with ≥ 2 isolates. Antimicrobial susceptibility varied substantially among clonotypes but was consistent across different locations. Clonotype-guided antimicrobial selection significantly reduced "drug-bug" mismatch compared to that which occurs with the use of conventional empirical therapy. With trimethoprim-sulfamethoxazole and fluoroquinolones, the drug-bug mismatch was predicted to decrease 62% and 78%, respectively. Recurrent or persistent urinary tract infection and clinical sepsis were significantly correlated with specific clonotypes, especially with CH40-30 (also known as H30), a recently described clonotype within sequence type 131 (ST131). We were able to clonotype directly from patient urine samples within 1 to 3 h of obtaining the specimen. In E. coli, subspecies-level identification by clonotyping can be used to significantly improve empirical predictions of antimicrobial susceptibility and clinical outcomes in a timely manner.


Assuntos
Farmacorresistência Bacteriana , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/microbiologia , Escherichia coli/classificação , Escherichia coli/efeitos dos fármacos , Tipagem Molecular , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Proteínas de Escherichia coli/genética , Feminino , Alemanha , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Resultado do Tratamento , Estados Unidos , Adulto Jovem
3.
Appl Environ Microbiol ; 78(5): 1353-60, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22226951

RESUMO

Multilocus sequence typing (MLST) is usually based on the sequencing of 5 to 8 housekeeping loci in the bacterial chromosome and has provided detailed descriptions of the population structure of bacterial species important to human health. However, even strains with identical MLST profiles (known as sequence types or STs) may possess distinct genotypes, which enable different eco- or pathotypic lifestyles. Here we describe a two-locus, sequence-based typing scheme for Escherichia coli that utilizes a 489-nucleotide (nt) internal fragment of fimH (encoding the type 1 fimbrial adhesin) and the 469-nt internal fumC fragment used in standard MLST. Based on sequence typing of 191 model commensal and pathogenic isolates plus 853 freshly isolated clinical E. coli strains, this 2-locus approach-which we call CH (fumC/fimH) typing-consistently yielded more haplotypes than standard 7-locus MLST, splitting large STs into multiple clonal subgroups and often distinguishing different within-ST eco- and pathotypes. Furthermore, specific CH profiles corresponded to specific STs, or ST complexes, with 95% accuracy, allowing excellent prediction of MLST-based profiles. Thus, 2-locus CH typing provides a genotyping tool for molecular epidemiology analysis that is more economical than standard 7-locus MLST but has superior clonal discrimination power and, at the same time, corresponds closely to MLST-based clonal groupings.


Assuntos
Escherichia coli/classificação , Escherichia coli/genética , Tipagem Molecular/métodos , Adesinas de Escherichia coli/genética , Análise por Conglomerados , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Proteínas de Fímbrias/genética , Genótipo , Humanos , Epidemiologia Molecular/métodos
4.
mBio ; 4(6): e00377-13, 2013 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-24345742

RESUMO

UNLABELLED: The Escherichia coli sequence type 131 (ST131) clone is notorious for extraintestinal infections, fluoroquinolone resistance, and extended-spectrum beta-lactamase (ESBL) production, attributable to a CTX-M-15-encoding mobile element. Here, we applied pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing to reconstruct the evolutionary history of the ST131 clone. PFGE-based cluster analyses suggested that both fluoroquinolone resistance and ESBL production had been acquired by multiple ST131 sublineages through independent genetic events. In contrast, the more robust whole-genome-sequence-based phylogenomic analysis revealed that fluoroquinolone resistance was confined almost entirely to a single, rapidly expanding ST131 subclone, designated H30-R. Strikingly, 91% of the CTX-M-15-producing isolates also belonged to a single, well-defined clade nested within H30-R, which was named H30-Rx due to its more extensive resistance. Despite its tight clonal relationship with H30Rx, the CTX-M-15 mobile element was inserted variably in plasmid and chromosomal locations within the H30-Rx genome. Screening of a large collection of recent clinical E. coli isolates both confirmed the global clonal expansion of H30-Rx and revealed its disproportionate association with sepsis (relative risk, 7.5; P < 0.001). Together, these results suggest that the high prevalence of CTX-M-15 production among ST131 isolates is due primarily to the expansion of a single, highly virulent subclone, H30-Rx. IMPORTANCE: We applied an advanced genomic approach to study the recent evolutionary history of one of the most important Escherichia coli strains in circulation today. This strain, called sequence type 131 (ST131), causes multidrug-resistant bladder, kidney, and bloodstream infections around the world. The rising prevalence of antibiotic resistance in E. coli is making these infections more difficult to treat and is leading to increased mortality. Past studies suggested that many different ST131 strains gained resistance to extended-spectrum cephalosporins independently. In contrast, our research indicates that most extended-spectrum-cephalosporin-resistant ST131 strains belong to a single highly pathogenic subclone, called H30-Rx. The clonal nature of H30-Rx may provide opportunities for vaccine or transmission prevention-based control strategies, which could gain importance as H30-Rx and other extraintestinal pathogenic E. coli subclones become resistant to our best antibiotics.


Assuntos
Epidemias , Infecções por Escherichia coli/microbiologia , Escherichia coli/classificação , Escherichia coli/enzimologia , beta-Lactamases/metabolismo , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Genótipo , Alemanha/epidemiologia , Humanos , Epidemiologia Molecular , Tipagem Molecular , Filogenia , Análise de Sequência de DNA , Estados Unidos/epidemiologia
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