I-Streptomycin potency ixhomekeke kwintetho yetshaneli ye-MscL

I-Streptomycin yayiyeyona ntsholongwane yokuqala ukufunyanwa kwiklasi ye-aminoglycoside kwaye ithathwe kwi-actinobacterium yentsholongwane.Streptomycesuhlobo1. Isetyenziswa ngokubanzi kunyango lwezifo ezinzulu zebhaktheriya ezibangelwa zombini iibhaktheriya ze-Gram-negative kunye ne-Gram-positive, kubandakanywa nesifo sephepha, isifo se-endocardial kunye ne-meningeal kunye nesibetho. Nangona isaziwa into yokuba eyona ndlela iphambili yesenzo se-streptomycin kukuthintelwa kweprotein synthesis ngokubopha i-ribosome, indlela yokungena kwiseli yebhaktiriya ayikacaci.

Ijelo leMechanosensitive ye-conductance enkulu (MscL) lijelo eligcinwe kakhulu lebhaktheriya elikwazi ukubona ngokuthe ngqo uxinzelelo kwi-membrane.2. Indima ye-physiological ye-MscL yileyo yevalve yokukhulula kaxakeka ethi ivuleke kwi-osmolarity yendalo (hypo-osmotic downshock)3. Ngaphantsi koxinzelelo lwe-hypo-osmotic, amanzi angena kwiseli yebhaktheriya ebangela ukuba idumbe, ngaloo ndlela inyusa uxinzelelo kwi-membrane; Amasango e-MscL ekuphenduleni le ngxabano eyenza i-pore enkulu malunga ne-30 Å4, ngaloo ndlela ivumela ukukhululwa ngokukhawuleza kwee-solutes kunye nokugcina iseli kwi-lysis. Ngenxa yobukhulu bepore, i-MscL gating ilawulwa ngokuqinileyo; Ukubonakaliswa kwe-mis-gating ye-MscL channel, evula ngaphantsi koxinzelelo oluqhelekileyo, kubangela ukukhula okucothayo kwebhaktheriya okanye ukufa kweeseli.5.

Iitshaneli ze-Bacterial mechanosensitive zicetywayo njengeethagethi ezifanelekileyo zamachiza ngenxa yendima yazo ebalulekileyo kwi-physiology yebhaktheriya kunye nokungabikho kwe-homologues ezichongiweyo kwizinto eziphezulu.6. Ngoko ke senza i-high-throughput screen (HTS) ukukhangela iikhompawundi eziza kuthintela ukukhula kwebhaktheriya ngendlela exhomekeke kwi-MscL. Okubangel 'umdla kukuba, phakathi kwee-hits sifumene izibulala-ntsholongwane ezine ezaziwayo, phakathi kwazo ezisetyenziswa kakhulu aminoglycosides antibiotics streptomycin and spectinomycin.

Amandla e-streptomycin axhomekeke kwintetho ye-MscL ekukhuleni nasekuzameni ukusebenzakwi vivo.Sikwabonelela ngobungqina bokumodareyithwa ngokuthe ngqo komsebenzi wetshaneli ye-MscL nge-dihydrostreptomycin kwi-patch clamp experiments.i-In vitro. Ukubandakanyeka kwe-MscL kwindlela yesenzo se-streptomycin akucebisi kuphela indlela entsha yendlela le molekyuli enkulu kunye ne-polar ephezulu ifumana ukufikelela kwiseli kwiindawo eziphantsi, kodwa kunye nezixhobo ezitsha zokumodareyitha amandla asele aziwayo kunye ne-antibiotics.


Ixesha lokuposa: Jul-11-2023