RESUMO
The role of the type-three secretion system of the gram-negative bacteria in regulation of chronic infections is discussed. Recent research showed that most of severe chronic somatic diseases are derived from chronic infection induced in the first place by infectious agents. The role of the T3SS of different species in transition from an acute infection to persistence is reviewed. Clinical and bacteriological research showed that microorganisms are persistent in the form resistant to antibiotics. That is why one of the promising targets for the development of antibacterial new-generation treatment is T3SS that conducts transport of bacteria pathogenicity factors into eukaryotic cell. The presence of this structure is necessary for the development of an acute infectious process and chronization of an infection is essential for its functioning.
Assuntos
Infecções Bacterianas , Sistemas de Secreção Bacterianos , Chlamydia , Salmonella , Yersinia , Infecções Bacterianas/genética , Infecções Bacterianas/metabolismo , Infecções Bacterianas/patologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sistemas de Secreção Bacterianos/genética , Sistemas de Secreção Bacterianos/fisiologia , Chlamydia/metabolismo , Chlamydia/patogenicidade , Doença Crônica , Resistência Microbiana a Medicamentos/genética , Humanos , Salmonella/metabolismo , Salmonella/patogenicidade , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Yersinia/metabolismo , Yersinia/patogenicidadeRESUMO
The Type III secretion system (T3SS) is currently considered to be one of the main pathogenicity factors in Gram-negative bacteria, which exhibit different types of parasitizing activity. The presence of this structure is essential for the development of an acute infection; the chronicity of the infection is fundamentally dependent upon its functioning. In this regard, T3TS is one of the most promising targets for the development of broad-spectrum antimicrobial drugs that do not develop resistance and are efficacious for the acute and chronic forms of infection. The mechanism of action in drug development is based on the specific inhibition of T3SS, which should interrupt the infectious process, thereby enabling the immune system to eliminate the pathogen. As a result of pilot screening using specific cellular and bacterial tests, followed by chemical optimization and detailed characterization of the biological activity, a new class of chlamydial T3SS inhibitors was obtained. The selected compounds have obvious advantages over the currently available inhibitors of T3SS pathogens thanks to the high inhibitory activity of these compounds with minimal damaging effects on eukaryotic cells. Preclinical trials of the selected inhibitors are currently under way.