Iimveliso

I-Mycobacterium tuberculosis inokuqhubeka amashumi eminyaka kumkhosi womntu.Iindlela zokuphendula ezingqongqo ezibandakanya i-polyphosphate ye-inorganic [poly(P)], edityanisiweyo kunye ne-hydrolyzed yi-polyphosphate kinase (PPK) kunye ne-exopolyphosphatase (PPX), ngokulandelelana, kukholelwa ukuba idlala indima ephambili yokulawula ukuzingisa kwebhaktheriya.Sibonisa apha ukuba i-M. tuberculosis poly(P) yokuqokelelana inxulunyaniswe okwethutyana nothintelo lokukhula kwe-bacillary.Sikwachonga i-M. tuberculosis Rv1026 njengenoveli exopolyphosphatase enomsebenzi we-hydrolytic ngokuchasene ne-long-chain poly(P).Ukusebenzisa inkqubo yokubonisa ye-tetracycline-inducible ukuwisa intetho ye-Rv1026 (ppx2), sifumanise ukuba i-M. tuberculosis poly(P) iqokelele ikhokelela ekukhuleni okucothayo kunye nokunciphisa ukukhuseleka kwi-isoniazid, ukunyuka kokumelana nobushushu kunye ne-asidi pH, kunye nokuphucula impilo ye-intracellular. ngexesha losulelo lwe-macrophage.Ngosasazo lwe-electron microscopy, i-ppx2 yokugobhoza uhlobo ibonise ukwanda kobukhulu bodonga lweeseli, olwayanyaniswa nokungenwa kodonga lweseli oluncitshisiweyo kumachiza e-hydrophilic endaweni yokufakwa kweempompo ze-efflux yechiza okanye ukwakheka kwe-biofilm etshintshiweyo ngokunxulumene nolawulo olungenanto lwe-vector.Uhlalutyo lwe-Transcriptomic kunye ne-metabolomic lubonise ukuhla kwe-metabolic downshift ye-ppx2 ye-knockdown ebonakaliswe ngokunciphisa ukukhutshelwa kunye nokuguqulelwa kunye nokunciphisa amanqanaba e-glycerol-3-phosphate.Ngamafutshane, i-poly(P) idlala indima ebalulekileyo kuthintelo lokukhula kwesifo sephepha kunye ne-metabolic downshift kwaye inegalelo kunyamezelo lwamayeza okubulala iintsholongwane ngokuguquguquka kodonga lweseli.Impendulo engqongqo, ebandakanya iimolekyuli zokulawula i-polyphosphate [poly(P)] kunye (p ) ppGpp, kukholeleka ukuba ilamla ukuqhubekeka kwesifo sephepha seMycobacterium.Kolu phononongo, sichonge i-enzyme yenoveli (i-Rv1026, i-PPX2) ejongene ne-hydrolyzing ye-poly-chain chain (P).Uhlobo lwesifo sephepha lwe-M. olwenziwe ngokwemfuza olunqongopheleyo kwi-ppx2 yemfuza lubonise amanqanaba epoly(P) anyukileyo, anxulunyaniswa nokubanjwa kokukhula kwebhaktiriya kwangoko kunye nokunciphisa ukuqina kwe-susce kwiyeza lokuqala i-isoniazid, kunye nokonyuka kokusinda kwebhaktiriya ngexesha lokuvezwa kuxinzelelo. iimeko kwaye ngaphakathi macrophages.Ngokubhekiselele kuxinzelelo lolawulo, i-mutant ibonise ukwanda kobunzima bodonga lweseli kunye nokuncipha kokungena kweziyobisi.Ukuchazwa kofuzo lwehlabathi jikelele kunye nohlalutyo lwe-metabolite lubonakalise ukuchazwa okuncitshisiweyo koomatshini bokukhutshelwa kunye noguqulo kunye nokutshintsha kokusetyenziswa komthombo wekhabhoni.Isishwankathelo, ukulawulwa kwe-poly (P) ibhalansi ibalulekile ekuqhubekeni kokwakheka kwi-M. tuberculosis.