Ƙarfin Streptomycin ya dogara da maganganun tashar MscL

Streptomycin shine maganin rigakafi na farko da aka gano a cikin ajin aminoglycoside kuma an samo shi daga actinobacterium naStreptomycesjinsi1. Ana amfani da ita sosai wajen magance cututtuka masu tsanani na ƙwayoyin cuta da ƙwayoyin cuta na Gram-negative da Gram-positive suke haifar da su, ciki har da tarin fuka, endocardial da cututtuka na meningeal da annoba. Ko da yake an san cewa tsarin farko na aikin streptomycin shine ta hanyar hana haɓakar furotin ta hanyar ɗaure ribosome, hanyar shiga cikin kwayar cutar ba ta bayyana ba tukuna.

Mechanosensitive tashar na babban conductance (MscL) shi ne mai matukar kiyayewa kwayoyin mechanosensitive tashar cewa kai tsaye jin tashin hankali a cikin membrane.2. Matsayin ilimin lissafin jiki na MscL shine na bawul ɗin saki na gaggawa wanda ke ƙofofin kan raguwa mai ƙarfi a cikin osmolarity na muhalli (hypo-osmotic downshock)3. Ƙarƙashin damuwa na hypo-osmotic, ruwa yana shiga cikin kwayoyin halitta yana haifar da kumburi, don haka ƙara tashin hankali a cikin membrane; Ƙofofin MscL don mayar da martani ga wannan tashin hankali yana haifar da babban pore na kimanin 30 Å4, don haka ba da izini don saurin sakin solutes da ceton tantanin halitta daga lysis. Saboda girman girman pore, MscL gating an daidaita shi sosai; Maganar tashar MscL mai kuskure, wacce ke buɗewa a ƙasa da tashe-tashen hankula, yana haifar da jinkirin haɓakar ƙwayoyin cuta ko ma mutuwar tantanin halitta.5.

An gabatar da tashoshi na injiniyoyin ƙwayoyin cuta a matsayin ingantattun maƙasudin miyagun ƙwayoyi saboda muhimmiyar rawar da suke takawa a cikin ilimin halittar ƙwayoyin cuta da kuma rashin gano nau'ikan homologues a cikin manyan halittu.6. Don haka mun yi babban allo mai ƙarfi (HTS) yana neman mahaɗan da za su hana ci gaban ƙwayoyin cuta ta hanyar dogaro da MscL. Abin sha'awa, a cikin hits mun sami sanannun maganin rigakafi guda huɗu, daga cikinsu ana amfani da maganin rigakafi na aminoglycosides streptomycin da spectinomycin.

Ƙarfin streptomycin ya dogara ne akan magana ta MscL a cikin haɓaka da gwaje-gwajen yuwuwain vivo.Har ila yau, muna ba da shaida na daidaitawa kai tsaye na ayyukan tashar MscL ta hanyar dihydrostreptomycin a cikin gwaje-gwajen manne.in vitro. Shigar da MscL a cikin hanyar aikin streptomycin yana ba da shawarar ba kawai wani sabon salo na yadda wannan ƙaƙƙarfan ƙwayar cuta mai ƙarfi ke samun damar shiga cikin tantanin halitta a ƙananan ƙima, har ma da sabbin kayan aiki don daidaita ƙarfin da aka riga aka sani da maganin rigakafi.


Lokacin aikawa: Jul-11-2023