RESUMO
The fsr locus of Enterococcus faecalis confers virulence in animal models. A retrospective analysis of fsr prevalence in diverse E. faecalis clinical isolates demonstrated fsr in all endocarditis isolates versus 53% of stool isolates (P = 0.005). This supports a role for fsr-mediated virulence in the pathogenesis of enterococcal infections in humans.
Assuntos
Enterococcus faecalis/genética , Enterococcus faecalis/patogenicidade , Genes Bacterianos , Infecções por Bactérias Gram-Positivas/microbiologia , Animais , Proteínas de Bactérias/genética , Sequência de Bases , DNA Bacteriano/genética , Endocardite Bacteriana/microbiologia , Humanos , Estudos Retrospectivos , Virulência/genéticaRESUMO
We assessed the ability of gene transfer to reverse vancomycin resistance in class A (VanA) glycopeptide-resistant Enterococcus faecalis. Recombinant shuttle vectors containing a vanH promoter-vanA antisense gene cassette fully restored vancomycin susceptibility through a combined transcriptional activator binding domain decoy and inducible vanA antisense RNA effect.
Assuntos
Antibacterianos/farmacologia , Enterococcus faecalis/genética , Oligonucleotídeos Antissenso/farmacologia , Resistência a Vancomicina/genética , Vancomicina/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Carbono-Oxigênio Ligases/antagonistas & inibidores , Carbono-Oxigênio Ligases/genética , Interações Medicamentosas , Enterococcus faecalis/efeitos dos fármacos , Técnicas de Transferência de Genes , Vetores Genéticos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Oligonucleotídeos Antissenso/genética , Transformação BacterianaRESUMO
The rate of viral replication appears to play a pivotal role in human immunodeficiency virus type 1 (HIV-1) pathogenesis and disease progression as it outstrips the capacity of the immune system to respond. Important cellular sites for HIV-1 production include T lymphocytes and tissue macrophages. Antiviral strategies, including newer treatment modalities such as gene therapy of HIV-1-susceptible cell populations, must be capable of engendering durable inhibitory effects to HIV-1 replication in both of these primary cell types in order to be effective. Among the potential genetic targets for intervention in the HIV-1 life cycle, the Rev regulatory system, consisting of Rev and its binding site, the Rev-responsive element (RRE), stands out as particularly attractive. Rev is essential for maintaining the stability of the viral genomic RNA as well as viral mRNAs encoding key structural and regulatory proteins. Moreover, it exhibits favorable threshold kinetics, in that Rev concentrations must rise above a critical level to exert their effect. To disable Rev function, primary T cells or macrophages were transduced with anti-Rev single-chain immunoglobulin (SFv) or RRE decoy genes either singly or in combination by employing adeno-associated virus vectors and then challenged with HIV-1. By directing both a protein and a nucleic acid against the normal interaction between Rev and the RRE, this genetic antiviral strategy effectively inhibited infection by either clinical or laboratory virus isolates. These results provide a framework for novel interventions to reduce virus production in the infected host.