I-Streptomycin kwakuyi-antibiotic yokuqala ukutholwa ekilasini le-aminoglycoside futhi isuselwa ku-actinobacterium ye-aminoglycoside.I-Streptomycesuhlobo1. Isetshenziswa kabanzi ekwelapheni izifo ezingathi sína zebhaktheriya ezibangelwa kokubili amagciwane e-Gram-negative kanye ne-Gram-positive, okuhlanganisa isifo sofuba, izifo ze-endocardial kanye ne-meningeal kanye nesifo. Nakuba kwaziwa ukuthi indlela eyinhloko yokusebenza kwe-streptomycin iwukuvinjwa kwamaprotheni synthesis ngokubopha i-ribosome, indlela yokungena engqamuzaneni yebhaktheriya ayikacaci.
Ishaneli ye-Mechanosensitive conductance enkulu (MscL) iyishaneli egcinwe kakhulu ye-bacterial mechanosensitive ezwa ngokuqondile ukungezwani kulwelwesi.2. Iqhaza elingokomzimba le-MscL yileyo yevalvu yokukhululwa ezimweni eziphuthumayo engena ekwehleni okukhulu kwe-osmolarity yendawo (hypo-osmotic downshock)3. Ngaphansi kokucindezeleka kwe-hypo-osmotic, amanzi angena engqamuzaneni lebhaktheriya elibangela ukuba livuvukale, ngaleyo ndlela andise ukungezwani kulwelwesi; Amasango e-MscL ekuphenduleni lokhu kucindezeleka okwenza imbobo enkulu engaba ngu-30 Å4, ngaleyo ndlela ivumela ukukhululwa okusheshayo kwama-solutes nokulondoloza iseli kusuka ku-lysis. Ngenxa yobukhulu obukhulu bembotshana, i-MscL gating ilawulwa ngokuqinile; ukubonakaliswa kwesiteshi se-MscL esingesihle, esivuleka ngaphansi kwezimo ezivamile, kubangela ukukhula kancane kwebhaktheriya noma ngisho nokufa kweseli.5.
Iziteshi ze-bacterial mechanosensitive ziye zahlongozwa njengezinhloso ezifanele zezidakamizwa ngenxa yendima yazo ebalulekile ku-physiology yamagciwane kanye nokuntuleka kwama-homologue ahlonziwe ezintweni eziphilayo eziphezulu.6. Ngakho-ke senze isikrini se-high-throughput (HTS) sicinga izinhlanganisela ezizovimbela ukukhula kwamagciwane ngendlela encike ku-MscL. Kuyathakazelisa ukuthi phakathi kwamahithi sithole ama-antibiotics amane aziwayo, phakathi kwawo ama-aminoglycosides asetshenziswa kakhulu ama-antibiotic streptomycin kanye ne-spectinomycin.
Amandla e-streptomycin ancike ekukhulumeni kwe-MscL ekuhlolweni kokukhula nokusebenzange vivo.Siphinde sinikeze ubufakazi bokushintshwa okuqondile komsebenzi wesiteshi se-MscL nge-dihydrostreptomycin ekuhlolweni kwe-patch clamp.ku-vitro. Ukubandakanyeka kwe-MscL endleleni yesenzo se-streptomycin akusikiseli kuphela indlela entsha yokuthi le molekyuli enkulu futhi ene-polar ithola kanjani ukufinyelela kungqamuzana ekugxilweni okuphansi, kodwa futhi namathuluzi amasha okulinganisa amandla emithi elwa namagciwane eyaziwa kakade futhi engase ibe khona.
Isikhathi sokuthumela: Jul-11-2023