Estudio de la resistencia a macrólidos, lincosamidas y estreptograminas en los microorganismos productores

Se estudia el mecanismo de resistencia a algunos antibióticos pertenecientes a los macrólidos lincosamidas y estreptograminas a nivel del sitio de acción del antibiótico presencia de enzimas inactivantes y existencia de una barrera de permeabilidad en los microorganismos productores de estos antibióticos. Todos los productores mostraron sensibilidad ribosómica para su propio antibiótico observado mediante ensayos de síntesis de proteínas in vitro. Se observo una disminución de la permeabilidad al propio antibiótico comparada con la de un microorganismo control para los productores de macrólidos y lincomicina. Los microorganismos productores de estreptograminas mostraron activad enzimática inactivante para estreptograminas tipo b que no preciso la presencia de cofactores. Por otra parte se compararon los patrones proteicos de los ribosomas de 7 especies de streptomyces valoradas por geles de poliocrilamida y cromatografía liquida de alta eficacia se observaron semejanzas y diferencias entre ellos y se propuso como un potencial método utilizable con fines taxonómicos

Cytosolic acidification is the first transduction signal of lactoferrin-induced regulated cell death pathway

In yeast, we reported the critical role of K+-efflux for the progress of the regulated cell death (RCD) induced by human lactoferrin (hLf), an antimicrobial protein of the innate immune system that blocks Pma1p H+-ATPase. In the present study, the K+ channel Tok1p was identified as the K+ channel-mediating K+-efflux, as indicated by the protective effect of extracellular K+ (≥30 mM), K+-channel blockers, and the greater hLf-resistance of TOK1-disrupted strains. K+-depletion was necessary but not sufficient to induce RCD as inferred from the effects of valinomycin, NH4Cl or nigericin which released a percentage of K+ similar to that released by lactoferrin without affecting cell viability. Cytosolic pH of hLf-treated cells decreased transiently (~0.3 pH units) and its inhibition prevented the RCD process, indicating that cytosolic acidification was a necessary and sufficient triggering signal. The blocking effect of lactoferrin on Pma1p H+-ATPase caused a transitory decrease of cytosolic pH, and the subsequent membrane depolarization activated the voltage-gated K+ channel, Tok1p, allowing an electrogenic K+-efflux. These ionic events, cytosolic accumulation of H+ followed by K+-efflux, constituted the initiating signals of this mitochondria-mediated cell death. These findings suggest, for the first time, the existence of an ionic signaling pathway in RCD