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1.
Infect Immun ; 85(8)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28559403

RESUMO

Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Additionally, B. bronchiseptica is capable of establishing long-term or chronic infections in swine. Bacterial biofilms are increasingly recognized as important contributors to chronic bacterial infections. Recently the polysaccharide locus bpsABCD has been demonstrated to serve a critical role in the development of mature biofilms formed by the sequenced laboratory strain of B. bronchiseptica We hypothesized that swine isolates would also have the ability to form mature biofilms and the bpsABCD locus would serve a key role in this process. A mutant containing an in-frame deletion of the bpsABCD structural genes was constructed in a wild-type swine isolate and found to be negative for poly-N-acetylglucosamine (PNAG)-like material by immunoblot assay. Further, the bpsABCD locus was found to be required for the development and maintenance of the three-dimensional structures under continuous-flow conditions. To investigate the contribution of the bpsABCD locus to the pathogenesis of B. bronchiseptica in swine, the KM22Δbps mutant was compared to the wild-type swine isolate for the ability to colonize and cause disease in pigs. The bpsABCD locus was found to not be required for persistence in the upper respiratory tract of swine. Additionally, the bpsABCD locus did not affect the development of anti-Bordetella humoral immunity, did not contribute to disease severity, and did not mediate protection from complement-mediated killing. However, the bpsABCD locus was found to enhance survival in the lower respiratory tract of swine.


Assuntos
Biofilmes/crescimento & desenvolvimento , Infecções por Bordetella/microbiologia , Bordetella bronchiseptica/patogenicidade , Polissacarídeos Bacterianos/metabolismo , Traqueia/microbiologia , Animais , Proteínas de Bactérias/genética , Infecções por Bordetella/imunologia , Bordetella bronchiseptica/química , Bordetella bronchiseptica/genética , Bordetella bronchiseptica/imunologia , Brônquios/microbiologia , Regulação Bacteriana da Expressão Gênica , Mutação , Nariz/microbiologia , Suínos
2.
J Med Chem ; 59(19): 8879-8888, 2016 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-27585401

RESUMO

Competitive quorum sensing (QS) antagonism offers a novel strategy for attenuating current multidrug resistant staphylococcal infections. To this end, a series of 10 truncated analogues based on the parent autoinducing peptides (AIPs) of Staphylococcus lugdunensis (groups I and II) and Staphylococcus epidermidis (groups I-III) were sequentially assessed against a newly developed Staphylococcus lugdunensis group I QS reporter strain. The truncated analogues based upon Staphylococcus lugdunensis AIP-1 (1) and AIP-2 (2) displayed respective IC50 values of 0.2 ± 0.01 µM and 0.3 ± 0.01 µM, while the truncated analogue of the Staphylococcus epidermidis AIP-1 (3) elicited an IC50 value of 2.7 ± 0.1 µM. These findings demonstrate the potential of cognate and "crosstalk" competitive quorum sensing inhibition using truncated AIPs as a means of attenuating staphylococcal infections in species beyond Staphylococcus aureus.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/farmacologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Percepção de Quorum/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus lugdunensis/efeitos dos fármacos , Descoberta de Drogas , Humanos , Modelos Moleculares , Infecções Estafilocócicas/microbiologia , Staphylococcus epidermidis/química , Staphylococcus lugdunensis/fisiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-25566513

RESUMO

Staphylococcus aureus is a major cause of nosocomial and community-acquired infections and represents a significant burden on the healthcare system. S. aureus attachment to medical implants and host tissue, and the establishment of a mature biofilm, play an important role in the persistence of chronic infections. The formation of a biofilm, and encasement of cells in a polymer-based matrix, decreases the susceptibility to antimicrobials and immune defenses, making these infections difficult to eradicate. During infection, dispersal of cells from the biofilm can result in spread to secondary sites and worsening of the infection. In this review, we discuss the current understanding of the pathways behind biofilm dispersal in S. aureus, with a focus on enzymatic and newly described broad-spectrum dispersal mechanisms. Additionally, we explore potential applications of dispersal in the treatment of biofilm-mediated infections.


Assuntos
Biofilmes , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Animais , Biofilmes/crescimento & desenvolvimento , Humanos , Staphylococcus aureus/genética , Staphylococcus aureus/crescimento & desenvolvimento
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