Nā huahana

Hiki i ka Mycobacterium tuberculosis ke hoʻomau i nā makahiki he mau makahiki i loko o ke kanaka.ʻO nā ala pane koʻikoʻi e pili ana i ka polyphosphate inorganic [poly(P)], i hoʻohui ʻia a hydrolyzed e polyphosphate kinase (PPK) a me exopolyphosphatase (PPX), i kēlā me kēia, ua manaʻo ʻia he kuleana koʻikoʻi i ka hoʻomau ʻana i ka bacteria.Hōʻike mākou ma ʻaneʻi ʻo ka hōʻiliʻili ʻana o ka M. tuberculosis poly(P) i hoʻopili ʻia me ka palena o ka ulu ʻana o ka bacillary.Hoʻomaopopo pū mākou i ka M. tuberculosis Rv1026 ma ke ʻano he exopolyphosphatase novel me ka hana hydrolytic e kūʻē i ka poly (P).Ke hoʻohana nei i kahi ʻōnaehana hōʻike tetracycline-inducible e kuʻi i ka hōʻike o Rv1026 (ppx2), ua ʻike mākou ʻo M. tuberculosis poly(P) accumulation alakaʻi i ka ulu lohi a hoʻemi i ka susceptibility i ka isoniazid, hoʻonui i ke kū'ē i ka wela a me ka pH acid, a hoʻonui i ke ola intracellular. i ka wā o ka maʻi macrophage.Ma ka lawe ʻana i ka microscopy electron, ua hōʻike ʻia ka ppx2 knockdown strain i ka mānoanoa o ka paia o ka cell cell, i pili me ka hoʻohaʻahaʻa ʻana o ka paia o ka paia cell i nā lāʻau hydrophilic ma mua o ka hoʻokomo ʻana i nā pamu efflux lāʻau a i ʻole ka hoʻololi ʻana i ke ʻano biofilm e pili ana i ka mana vector ʻole.Ua hōʻike ʻia ka loiloi transcriptomic a me ka metabolomic i kahi metabolic downshift o ka ppx2 knockdown i hōʻike ʻia e ka hōʻemi ʻana i ka transcription a me ka unuhi ʻana a me kahi iho o nā pae glycerol-3-phosphate.I ka hōʻuluʻulu manaʻo, he mea koʻikoʻi ka poly(P) i ka M. tuberculosis ka palena o ka ulu ʻana a me ka metabolic downshift a hāʻawi i ka ʻae ʻana i ka antibiotic ma o ka hoʻololi ʻana i ka paia o ka pā hale. )ppGpp, ua manaʻo ʻia e uwao i ka hoʻomau ʻana o ka Mycobacterium tuberculosis.Ma kēia haʻawina, ua ʻike mākou i kahi enzyme hou (Rv1026, PPX2) kuleana no ka hydrolyzing long-chain poly(P).Ua hōʻike ʻia kahi maʻi M. tuberculosis genetically engineered i ka gene ppx2 i ka piʻi ʻana o nā pae poly(P), i pili pū me ka hopu ʻana i ka ulu ʻana o ka maʻi bacterial mua a hoʻemi i ka hiki i ka lāʻau lapaʻau isoniazid laina mua, a me ka piʻi ʻana o ke ola bacteria i ka wā e ʻike ai i ke kaumaha. nā kūlana a i loko o nā macrophages.E pili ana i ka mana hoʻomalu, ua hōʻike ka mutant i ka mānoanoa nui o ka paia cell a hoʻemi i ka permeability o ka lāʻau.Ua hōʻike ʻia ka hōʻike ʻana o ka gene global a me ka loiloi metabolite i ka hōʻemi ʻana o ka mīkini unuhi a me ka unuhi a me ka hoʻololi ʻana i ka hoʻohana kumu kalapona.I ka hōʻuluʻulu ʻana, he mea koʻikoʻi ka hoʻoponopono ʻana i ke koena poly(P) no ka hoʻomau mau ʻana i ka M. tuberculosis.