Zogulitsa

Mycobacterium TB ikhoza kukhalapo kwa zaka zambiri mwa munthu.Njira zoyankhira zolimba zomwe zimaphatikizapo inorganic polyphosphate [poly(P)], yomwe imapangidwa ndi hydrolyzed ndi polyphosphate kinase (PPK) ndi exopolyphosphatase (PPX), motsatana, akukhulupirira kuti amathandizira kwambiri kulimbikira kwa bakiteriya.Tikuwonetsa apa kuti kuchuluka kwa M. TB poly(P) kumalumikizidwa kwakanthawi ndikuletsa kukula kwa bacillary.Timazindikiranso M. TB Rv1026 ngati buku la exopolyphosphatase lomwe lili ndi zochita za hydrolytic motsutsana ndi poly-chain poly(P).Pogwiritsa ntchito tetracycline-inducible expression system kugwetsa mawu a Rv1026 (ppx2), tinapeza kuti M. tuberculosis poly(P) kudzikundikira kumabweretsa kukula pang'onopang'ono ndi kuchepetsa kutengeka kwa isoniazid, kuchulukitsidwa kukana kutentha ndi asidi pH, komanso kupulumuka kwa intracellular. pa matenda a macrophage.Pogwiritsa ntchito ma electron microscopy, ppx2 knockdown strain ikuwonetsa kuchuluka kwa khoma la cell, komwe kumalumikizidwa ndi kuchepetsedwa kwa khoma la cell ku mankhwala a hydrophilic m'malo molowetsa mapampu a efflux kapena kusintha mawonekedwe a biofilm poyerekeza ndi chowongolera chopanda kanthu.Kusanthula kwa Transcriptomic ndi metabolomic kunavumbulutsa kutsika kwa kagayidwe kazakudya kwa ppx2 kugogoda komwe kumadziwika ndi kuchepetsedwa kumasulira ndi kumasulira komanso kutsika kwa milingo ya glycerol-3-phosphate.Mwachidule, poly(P) imagwira ntchito yofunika kwambiri pakuletsa kukula kwa chifuwa chachikulu cha M. chifuwa chachikulu komanso kuchepa kwa kagayidwe kachakudya ndipo imathandizira kulekerera kwa maantibayotiki kudzera pakusinthika kwa khoma la khoma. ppGpp, amakhulupirira kuti amayimira kulimbikira kwa chifuwa chachikulu cha Mycobacterium.Mu kafukufukuyu, tazindikira puloteni yatsopano (Rv1026, PPX2) yomwe imayambitsa hydrolyzing long-chain poly(P).Matenda a chifuwa chachikulu a M. TB omwe alibe mphamvu mu ppx2 jini adawonetsa kuchuluka kwa ma poly(P), omwe amalumikizidwa ndi kumangidwa kwa bakiteriya koyambirira komanso kuchepetsa kutha kwa mankhwala a isoniazid, komanso kupulumuka kwa bakiteriya panthawi yamavuto. zinthu komanso mkati mwa macrophages.Mogwirizana ndi zovuta zowongolera, mutant adawonetsa makulidwe a khoma la cell ndikuchepetsa mphamvu yamankhwala.Kusanthula kwa majini padziko lonse lapansi ndi kusanthula kwa metabolite kunawonetsa kuchepa kwa makina olembera ndi omasulira komanso kusintha kwa kagwiritsidwe ntchito ka kaboni.Mwachidule, kuwongolera kuchuluka kwa poly(P) ndikofunikira pakulimbikira kupanga mu M. TB.