RESUMO
Phagocytic cells of the mammalian innate immune system play a critical role in protecting the body from bacterial infections. The multiple facets of this encounter (chemotaxis, phagocytosis, destruction, evasion and pathogenicity) are largely recapitulated in the phagocytic amoeba Dictyostelium discoideum. Here we identified a new chemical compound (K14; ZINC19168591) which inhibited intracellular destruction of ingested K. pneumoniae in D. discoideum cells. Concomitantly, K14 reduced proteolytic activity in D. discoideum phagosomes. In kil1 KO cells, K14 lost its ability to inhibit phagosomal proteolysis and to inhibit intra-phagosomal bacterial destruction, suggesting that K14 inhibits a Kil1-dependent protease involved in bacterial destruction. These observations stress the key role that proteases play in bacterial destruction. They also reveal an unsuspected link between Kil1 and phagosomal proteases. K14 can be used in the future as a tool to probe the role of different proteases in phagosomal physiology and in the destruction of ingested bacteria.
Assuntos
Dictyostelium , Peptídeo Hidrolases , Fagossomos , Dictyostelium/enzimologia , Fagossomos/metabolismo , Peptídeo Hidrolases/metabolismo , Fagocitose/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genéticaRESUMO
The opportunistic pathogen Klebsiella pneumoniae (K. pneumoniae) can colonize mucosal surfaces and spread from mucosae to other tissues, causing fatal infections. Medical equipment and the healthcare setting can become colonized by Klebsiella species, which are widely distributed in nature and can be found in water, soil, and animals. Moreover, a substantial number of community-acquired illnesses are also caused by this organism worldwide. These infections are characterized by a high rate of morbidity and mortality as well as the capacity to spread metastatically. Hypervirulent Klebsiella strains are thought to be connected to these infections. Four components are critical to this bacterium's pathogenicity-the capsule, lipopolysaccharide, fimbriae, and siderophores. Siderophores are secondary metabolites that allow iron to sequester from the surrounding medium and transport it to the intracellular compartment of the bacteria. A number of variables may lead to K. pneumoniae colonization in a specific area. Risk factors for infection include local healthcare practices, antibiotic use and misuse, infection control procedures, nutrition, gender, and age.