Imikhiqizo

Isifo sofuba se-Mycobacterium singaqhubeka amashumi eminyaka kumuntu.Izindlela zokuphendula eziqinile ezihlanganisa i-polyphosphate ye-inorganic [poly(P)], ehlanganiswa futhi ifakwe i-hydrolyzed yi-polyphosphate kinase (PPK) kanye ne-exopolyphosphatase (PPX), ngokulandelana, kukholakala ukuthi idlala indima ebalulekile yokulawula ekuphikeleleni kwamagciwane.Sibonisa lapha ukuthi ukunqwabelana kwe-M. tuberculosis poly(P) kuxhumene okwesikhashana nomkhawulo wokukhula kwe-bacillary.Siphinde sihlonze i-M. tuberculosis Rv1026 njengenoveli exopolyphosphatase enomsebenzi we-hydrolytic ngokumelene ne-long-chain poly(P).Sisebenzisa i-tetracycline-inducible expression system ukuze siwise isisho se-Rv1026 (ppx2), sithole ukuthi ukunqwabelana kwe-M. tuberculosis poly(P) kuholela ekukhuleni okunensayo kanye nokunciphisa amathuba okuba ne-isoniazid, ukumelana nokwanda kokushisa ne-asidi pH, kanye nokuphila okuthuthukisiwe kwe-intracellular. ngesikhathi sokutheleleka kwe-macrophage.Ngokudluliswa kwe-electron microscopy, uhlobo lwe-ppx2 knockdown lubonise ukushuba kodonga lwamaseli okwenyukile, okwakuhlotshaniswa nokufinyela kabusha kodonga lweseli emithini ye-hydrophilic esikhundleni sokufakwa kwamaphampu e-efflux yezidakamizwa noma ukwakheka kwe-biofilm okushintshile okuhlobene nokulawula i-vector engenalutho.Ukuhlaziywa kwe-Transcriptomic kanye ne-metabolomic kwembule ukwehliswa kwe-metabolic ye-ppx2 knockdown ebonakala ngokuloba okuncishisiwe nokuhumusha kanye nokwehla kwamazinga e-glycerol-3-phosphate.Kafushane, i-poly(P) idlala indima ebalulekile ekuvimbeleni ukukhula kofuba lwe-M. kanye nokwehla kwe-metabolic futhi inomthelela ekubekezeleni kwemithi elwa namagciwane ngokushintsha udonga lwamaseli.Impendulo eqinile, ebandakanya ama-molecule alawulayo i-polyphosphate ye-inorganic [poly(P)] kanye (p )ppGpp, kukholakala ukuthi ilamula ukuphikelela kwesifo sofuba se-Mycobacterium.Kulolu cwaningo, sihlonze i-enzayimu inoveli (Rv1026, PPX2) ebhekele ukwenziwa kwe-hydrolyzing long-chain poly(P).Ufuzo olwakhiwe ngofuzo lwe-M. uhlobo lwesifo sofuzo oluntula isakhi sofuzo lwe-ppx2 lubonise amazinga e-poly(P) anyukile, ayehlotshaniswa nokuboshwa kokuqala kwebhaktheriya kanye nokunciphisa ukuqina komuthi we-isoniazid womugqa wokuqala, kanye nokwanda kokusinda kwamagciwane ngesikhathi sokuchayeka ekucindezelekeni. izimo futhi ngaphakathi macrophages.Ngokuphathelene nobunzima bokulawula, i-mutant ibonise ukushuba okwandayo kodonga lweseli kanye nokuncipha kokungena kwezidakamizwa.Isisho sofuzo somhlaba wonke nokuhlaziywa kwe-metabolite kwembula ukubonakaliswa okuncishisiwe kwemishini yokubhala neyokuhumusha kanye nokushintsha kokusetshenziswa komthombo wekhabhoni.Kafushane, ukulawulwa kwebhalansi ye-poly(P) ibalulekile ekwakhekeni okuqhubekayo ku-M. tuberculosis.