Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Antibiot (Tokyo) ; 61(8): 489-95, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18997387

RESUMO

Rifampin-resistant mutants of the obligate intracellular pathogen Chlamydia pneumoniae were isolated and characterized, including strains that contained multiple mutations in the rpoB gene encoding the rifampin binding site. The highest MIC of rifampin against a mutant strain exceeded 100 microg/ml, whereas the highest MIC of rifalazil was 0.125 microg/ml. Derivatives of rifalazil (new chemical entities; NCEs) showed from 2 approximately 4 fold lower MICs, as well as 2 approximately 8 fold lower bactericidal concentrations against both wild type and mutant strains when compared with rifalazil. These results suggest that rifalazil and NCEs are appropriate therapeutic agents for the treatment of C. pneumoniae infections from the point of view of potency and resistance development.


Assuntos
Antibióticos Antituberculose/farmacologia , Chlamydophila pneumoniae/efeitos dos fármacos , Chlamydophila pneumoniae/genética , Mutação , Rifampina/farmacologia , Rifamicinas/farmacologia , Sequência de Aminoácidos , Linhagem Celular , Linhagem Celular Tumoral , Infecções por Chlamydophila/tratamento farmacológico , Infecções por Chlamydophila/microbiologia , Chlamydophila pneumoniae/crescimento & desenvolvimento , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Alinhamento de Sequência
2.
Infect Immun ; 76(12): 5438-46, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18852248

RESUMO

Clinical isolates of Chlamydia trachomatis that lack IncA on their inclusion membrane form nonfusogenic inclusions and have been associated with milder, subclinical infections in patients. The molecular events associated with the generation of IncA-negative strains and their roles in chlamydial sexually transmitted infections are not clear. We explored the biology of the IncA-negative strains by analyzing their genomic structure, transcription, and growth characteristics in vitro and in vivo in comparison with IncA-positive C. trachomatis strains. Three clinical samples were identified that contained a mixture of IncA-positive and -negative same-serovar C. trachomatis populations, and two more such pairs were found in serial isolates from persistently infected individuals. Genomic sequence analysis of individual strains from each of two serovar-matched pairs showed that these pairs were very similar genetically. In contrast, the genome sequence of an unmatched IncA-negative strain contained over 5,000 nucleotide polymorphisms relative to the genome sequence of a serovar-matched but otherwise unlinked strain. Transcriptional analysis, in vitro culture kinetics, and animal modeling demonstrated that IncA-negative strains isolated in the presence of a serovar-matched wild-type strain are phenotypically more similar to the wild-type strain than are IncA-negative strains isolated in the absence of a serovar-matched wild-type strain. These studies support a model suggesting that a change from an IncA-positive strain to the previously described IncA-negative phenotype may involve multiple steps, the first of which involves a translational inactivation of incA, associated with subsequent unidentified steps that lead to the observed decrease in transcript level, differences in growth rate, and differences in mouse infectivity.


Assuntos
Proteínas de Bactérias/genética , Chlamydia trachomatis/fisiologia , Chlamydia trachomatis/patogenicidade , Infecções por Chlamydiaceae/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana/genética , Animais , Sequência de Bases , Northern Blotting , Feminino , Humanos , Camundongos , Microscopia de Fluorescência , Dados de Sequência Molecular , Fenótipo , Polimorfismo Genético , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica
3.
J Infect Dis ; 192(7): 1229-36, 2005 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-16136466

RESUMO

We compared growth rate and host-cell transcriptional responses of a Chlamydia trachomatis variant strain and a prototype strain. Growth dynamics were estimated by 16S rRNA level and by inclusion-forming units (IFUs) at different times after infection in HeLa cells. When inoculated at the same multiplicity of infection and observed 24-48 h after infection, the variant 16S rRNA transcriptional level was 3%-4% that of the prototype, and the IFUs of the variant strain were 0.1%-1% those of the prototype. Specific host-cell transcriptional responses to the variant were identified in a global-expression microarray in which variant strain-infected cells were compared with mock-infected and prototype strain-infected cells. In variant strain-infected cells, 47% (16/34) of specifically induced host genes were related to immunity and 32% (8/25) of specifically suppressed genes were related to lipid metabolism. The variant strain grew significantly more slowly and induced a modified host-cell transcriptional response, compared with the prototype strain.


Assuntos
Chlamydia trachomatis/crescimento & desenvolvimento , Chlamydia trachomatis/patogenicidade , Variação Genética , Corpos de Inclusão/metabolismo , Proteínas/metabolismo , Chlamydia trachomatis/classificação , Chlamydia trachomatis/genética , Regulação da Expressão Gênica , Células HeLa/imunologia , Células HeLa/microbiologia , Humanos , Lipídeos/biossíntese , Fusão de Membrana , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas/genética , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica
4.
Antimicrob Agents Chemother ; 49(9): 3974-6, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16127086

RESUMO

Rifalazil, a semisynthetic rifamycin, was shown previously to have exceptional potency against Chlamydia trachomatis (MIC of 0.00025 microg/ml). We therefore tested 250 additional rifamycin derivatives and identified 12 with activities that are eightfold more potent than that of rifalazil. These compounds also showed exceptional activities against rifampin-resistant strains that carry missense mutations in the rpoB gene. The antimicrobial potency and intracellular penetration of these agents suggest their potential in treatment of chlamydial infections.


Assuntos
Antibacterianos/farmacologia , Chlamydia trachomatis/efeitos dos fármacos , Chlamydia trachomatis/genética , Rifamicinas/farmacologia , Infecções por Chlamydia/microbiologia , Humanos , Mutação de Sentido Incorreto
5.
J Infect Dis ; 187(3): 424-34, 2003 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-12552426

RESUMO

To study the responses of the host cell to chlamydial infection, differentially transcribed genes of the host cells were examined. Complementary DNA (cDNA) probes were made from messenger RNAs of HeLa cells infected with Chlamydia trachomatis and were hybridized to a high-density human DNA microarray of 15,000 genes and expressed sequence tags. C. trachomatis alters host cell transcription at both the early and middle phases of its developmental cycle. At 2 h after infection, 13 host genes showed mean expression ratios >/=2-fold. At 16 h after infection, 130 genes were differentially transcribed. These genes encoded factors inhibiting apoptosis and factors regulating cell differentiation, components of the cytoskeleton, transcription factors, and proinflammatory cytokines. This indicates that chlamydial infection, despite its intravacuolar location, alters the transcription of a broad range of host genes in diverse cellular pathways and provides a framework for future studies.


Assuntos
Infecções por Chlamydia/genética , Infecções por Chlamydia/patologia , Chlamydia trachomatis/fisiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Transdução de Sinais , Transcrição Gênica/genética , Infecções por Chlamydia/microbiologia , DNA Complementar/genética , Células HeLa , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...