Kev Tshawb Fawb Kev Txhim Kho Ntawm Cov Tshuaj Tiv Thaiv Kab Mob Ntawm Cov Tsob Ntoo Extracts Thiab Cov Tshuaj Tua Kab Mob Ⅱ
Sep 18, 2024
3 Synergistic antibacterial mechanism ntawm cov nroj tsuag rho tawm thiab tshuaj tua kab mob
Cov nroj tsuag tuaj yeem txhim kho qhov kev nkag siab ntawm cov kab mob rau cov tshuaj tua kab mob los ntawm inhibiting cov haujlwm ntawm cov tshuaj tua kab mob hydrolysis / hloov enzymes, hloov kho cov hom phiaj tshuaj tua kab mob, inhibiting efflux twj efflux, nce membrane permeability, thiab inhibiting / clearing biofilms.

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3.1 Inhibition ntawm tshuaj tua kab mob hydrolysis / hloov kho enzyme kev ua
-lactamase muaj peev xwm hydrolyze thiab rhuav tshem penicillin, cephalosporin, thiab carbapenem tshuaj tua kab mob, thiab yog lub ntsiab ua rau cov tshuaj tua kab mob inactivation, yog li ua rau cov kab mob tsis kam mus rau -lactam tshuaj tua kab mob[28]. Nroj tsuag rho tawm cov kab mob rhiab heev rau cov tshuaj tua kab mob los ntawm inhibiting -lactamase kev ua haujlwm. Teng et al. pom[29] tias theaflavin-3,3'-digallate (TFDG) thiab -lactam cov tshuaj tua kab mob muaj cov tshuaj tua kab mob sib xyaw ua ke ntawm MRSA, thiab txheeb xyuas cov txheej txheem inhibitory ntawm TFDG ntawm -lactamase los ntawm molecular dynamics simulation. Nws tau pom tias TFDG khi rau Gln 242 thiab Ser 369, yog li inhibiting hydrolysis ntawm -lactamase thiab ua rau MRSA rhiab heev rau -lactam tshuaj tua kab mob dua. Karumathil et al. tau kawm txog cov teebmeem ntawm trans-cinnamaldehyde (TC) thiab eugenol (EG) ua ke nrog 7 -lactam tshuaj tua kab mob ntawm ntau cov tshuaj tiv thaiv Acinetobacter baumannii thiab pom tias TC thiab EG ua ke nrog cov tshuaj tua kab mob tuaj yeem txhim kho qhov rhiab heev ntawm Acinetobacter baumannii rau tag nrho cov tshuaj tua kab mob. Nyob rau tib lub sijhawm, raws li RT-qPCR cov txiaj ntsig, TC thiab EG tau txo qis kev qhia ntawm feem ntau -lactam tshuaj tiv thaiv kab mob ntsig txog cov noob, tshwj xeeb tshaj yog blaP thiab adeAB. Nws tau pom tias TC thiab EG tswj cov kab mob ntawm cov tshuaj tiv thaiv ntau yam Acinetobacter los ntawm inhibiting -lactamase kev ua haujlwm [30]. Tsis tas li ntawd, tannic acid, epigallocatechin gallate [31], myricetin [32], kua txob tseem ceeb roj [33], thiab lwm yam tuaj yeem cuam tshuam -lactamase kev ua haujlwm hauv vitro thiab txhim kho cov tshuaj tua kab mob ntawm cov tshuaj tua kab mob.

3.2 Inhibition ntawm efflux twj tso kua mis efflux
Efflux twj (EP) yog ib qho tseem ceeb ntawm cov plasma membrane ntawm tag nrho cov kab mob. Lawv lees paub thiab tso tshuaj tua kab mob tawm ntawm lub xov tooj ua ntej cov tshuaj tua kab mob mus txog lub hom phiaj, txo cov ntsiab lus ntawm cov tshuaj intracellular thiab yog li txhim kho cov tshuaj tiv thaiv kab mob. Cov nroj tsuag muaj cov metabolites theem nrab nrog ntau hom tshuaj lom neeg thiab ntau yam khoom siv tshuaj. Ntau cov kev tshawb fawb txog kev rho tawm ntawm cov nroj tsuag tshuaj tau pom tias muaj cov molecules uas tuaj yeem thaiv cov twj efflux hauv cov kab mob Gram-negative thiab Gram-positive thiab rov ua kom muaj txiaj ntsig ntawm cov tshuaj tua kab mob, kom cov tshuaj tua kab mob sib sau mus rau qee qhov concentration hauv cov kab mob kom ua tiav cov kab mob bactericidal. nyhuv. Thaum genistein thiab genistein tau siv ua ke nrog norfloxacin, qib kev qhia ntawm NorA tau txo qis, thiab MIC tus nqi ntawm norfloxacin raug txo los ntawm 4 zaug, uas txhim kho cov kab mob tua kab mob ntawm quinolone tshuaj tua kab mob tiv thaiv MRSA [16]. DA et al. pom tias kua txob tseem ceeb roj tuaj yeem kho cov kab mob tua kab mob ntawm tetracycline thiab ciprofloxacin tiv thaiv ntau cov tshuaj tiv thaiv Staphylococcus aureus. Lub fluorescence emission spectrum tau lees paub tias cov tshuaj tua kab mob yog cov kua txob tseem ceeb roj inhibited cov dej num ntawm NorA thiab MepA efflux twj [33]. Thaum cov biflavonoids muab rho tawm los ntawm cov haiv neeg nyob rau sab hnub tuaj Amazon hauv Brazil tau siv ua ke nrog norfloxacin, lawv tuaj yeem cuam tshuam cov noob efflux xws li QacA/B, Tetk thiab MsrA ntawm Staphylococcus aureus, thiab MIC tus nqi ntawm norfloxacin raug txo los ntawm 8. xwm [34]. Dwivedi et al. pom tau tias vinblastine tuaj yeem txo qhov ntau npaum ntawm tetracycline thiab streptomycin rau cov tshuaj tiv thaiv kab mob sib txawv (KG-P2), thiab tuaj yeem txo cov cell viability. Nws tau kwv yees tias cov txheej txheem ntawm vinblastine qhov tsis kam thim rov qab tuaj yeem yog vim qhov inhibition ntawm efflux twj [35].

3.3 Inhibition los yog tshem tawm ntawm biofilms
Biofilm yog ib lub zej zog microbial txuas nrog rau cov kab mob lom neeg thiab tsis muaj kab mob. Kev tsim ntawm biofilm yog ib qho txheej txheem ntau kauj ruam uas cuam tshuam nrog kev hloov pauv ntawm cov kab mob los ntawm daim ntawv ua luam dej dawb planktonic mus rau ib daim ntawv ruaj khov ntawm biofilm tsim. Nws feem ntau suav nrog plaub cov kauj ruam tseem ceeb: txuas rau saum npoo ntawm cov khoom, kev loj hlob, tsim cov microcolonies, thiab kev loj hlob mus rau hauv cov zej zog cov kab ke thiab cov kab mob resistant [36]. Kev tsim ntawm biofilms pab txhawb kev txhim kho cov tshuaj tiv thaiv kab mob, uas yog lub hauv paus tseem ceeb vim li cas cov kab mob kis tau yooj yim los tswj. Cov nroj tsuag tuaj yeem cuam tshuam kev tsim cov biofilms ntawm ntau yam kab mob, thiab muaj kev puas tsuaj rau biofilms uas twb muaj lawm, txhawb kev nkag mus ntawm cov tshuaj tua kab mob, yog li thim rov qab cov kab mob. Kart et al. pom tias [13] qhov tsawg kawg nkaus biofilm inhibition concentration ntawm ciprofloxacin ua ke nrog curcumin, baicalein, thiab fraxinoyl tuaj yeem txo los ntawm 30 mus rau 60 npaug piv nrog ciprofloxacin ib leeg, qhia tias cov nroj tsuag rho tawm tuaj yeem siv ua ke nrog cov tshuaj tua kab mob los tiv thaiv lossis tshem tawm biofilms. Hauv kev kawm ntawm Bahari et al. [37], thaum azithromycin thiab gentamicin tau siv ua ke nrog curcumin, biofilm tsim ntawm Pseudomonas aeruginosa tau txo qis, thiab cov nyhuv inhibitory yog concentration-dependent. Tsis tas li ntawd, kev sib xyaw ntawm 1/4 MIC (64 µg / mL) azithromycin thiab 1/4 MIC (32 µg / mL) curcumin pom qhov cuam tshuam loj tshaj plaws ntawm kev loj hlob ntawm biofilms.

3.4 Ua kom cov membrane permeability
Qee cov kab mob downregulates refilling ntawm pore proteins los yog lwm yam kev xaiv protein raws, ua rau txo cell membrane permeability rau cov tshuaj tua kab mob, thiab txo cov tshuaj nkag mus rau hauv cov kab mob hlwb, yog li tsim tshuaj tua kab mob. Nroj tsuag extracts khi rau cov lipids ntawm cov kab mob ntawm cov kab mob cell membranes thiab rhuav tshem cov cell phab ntsa qauv, ua rau kev ncaj ncees puas tsuaj, pab txhawb cell membrane permeability thiab intracellular tshuaj tua kab mob cov ntsiab lus, cell ntsiab lus poob, thiab cell tuag [38]. Apinundecha et al. tau soj ntsuam cov teebmeem ntawm kev siv cov qhiav thiab cloxacillin ntawm MRSA siv cov tshuab ntsuas hluav taws xob thiab xa hluav taws xob hluav taws xob [39]. Thaum siv ua ke tshwm sim, dents, kab nrib pleb, vesicle lug, thiab pom tseeb cell lysis tshwm nyob rau saum npoo ntawm MRSA hlwb. Kev xau ntawm MRSA cell phab ntsa, cell membranes, thiab cov ntsiab lus ntawm tes hloov pauv, thiab cov tshuaj tua kab mob nkag mus rau hauv lub cell tau nce, uas qhia tau hais tias muaj txiaj ntsig zoo ntawm cov kab mob. Tsis tas li ntawd, cov nroj tsuag rho tawm tuaj yeem txhim kho cov cell membrane permeability ntawm cov kab mob Gram-negative. Qu et al. pom tias kev sib xyaw ua ke ntawm tetracycline thiab quercetin kuj muaj kev puas tsuaj rau kev ncaj ncees ntawm Escherichia coli cell membrane, nce nws cov permeability, nce qib ntawm -galactosidase thiab alkaline phosphatase, nce cov ntsiab lus ATP extracellular, thiab nce tetracycline uptake, yog li. inhibiting kev loj hlob ntawm Escherichia coli thiab ua rau ntau cov tshuaj tiv thaiv Escherichia coli rhiab rau tetracycline dua [15]. Thaum baicalein tau siv ua ke nrog doxycycline, fluorescence siv ntawm propidium iodide (PI) thiab 1-N-phenylnaphthylamine (NPN) thiab cov ntsiab lus extracellular ntawm -galactosidase thiab ATP nce. Cov kev tshawb fawb tau lees paub tias kev siv ua ke ntawm ob cov tshuaj tuaj yeem cuam tshuam kev sib txuas ntawm Mg 2+ rau lipid A los rhuav tshem cov cell membrane ntawm Gram-negative bacteria, yog li synergistically inhibiting kev loj hlob ntawm cov kab mob Gram-negative thiab txo lawv cov tshuaj. kev tiv thaiv [40].
3.5 Kev hloov kho tshuaj tua kab mob
Kev xaiv toxicity ntawm ntau cov tshuaj tua kab mob rau cov kab mob yog vim lawv cov affinity siab thiab tshwj xeeb rau cov hom kab mob. Tom qab khi rau lub hom phiaj, qhov sib txuas ntawm tes ua haujlwm yog inhibited, yog li cuam tshuam cov kab mob loj hlob lossis tuag taus. Ib qho tseem ceeb ntawm kev txiav txim siab ntawm cov kab mob tsis zoo rau cov tshuaj tua kab mob yog cov qauv kev hloov pauv lossis hloov kho cov hom phiaj tshuaj tua kab mob. Penicillin-binding protein 2a (PBP2a) yog ib qho enzyme uas catalyzes cross-linking cov tshuaj tiv thaiv ntawm ob sab peptide stems thaum lub sij hawm peptidoglycan biosynthesis, uas yuav txo tau cov tshuaj tua kab mob ntawm -lactam tshuaj tua kab mob thiab yog li induce tshuaj tua kab mob. Cov nroj tsuag rho tawm tuaj yeem ua rau kom muaj kev sib raug zoo ntawm cov kab mob rau -lactam tshuaj tua kab mob los ntawm inhibiting PBP2a, ua rau lawv rhiab rau cov tshuaj tua kab mob dua. Chang et al. pom tias kev sib xyaw ua ke ntawm tremazone thiab koob tshuaj qis qis oxacillin txo qhov kev qhia ntawm mecA thiab ua rau nws cov kab mob tua kab mob los ntawm kev tswj tsis zoo PBP2a ntawm MRSA, yog li txo nws txoj kev tiv thaiv. Wang et al. pom tias [42], thaum trans-cinnamaldehyde tau ua ke nrog yim cov tshuaj tua kab mob, cov tshuaj tua kab mob tuaj yeem txo los ntawm 2 txog 16 zaug. Thaum cov teebmeem ntawm trans-cinnamaldehyde ntawm mecA transcription gene thiab PBP2a ntawm MRSA tau txheeb xyuas los ntawm RT-PCR thiab Western-blot, nws tau pom tias ob qho tib si cov noob qoob loo thiab cov protein ntau tau cuam tshuam, qhia tias nws lub ntsiab mechanism yog los txo qhov tsim tawm PBP2a. Vankwani et al. tau lees paub qhov inhibitory nyhuv ntawm Moringa qia bark thiab ampicillin ntawm -lactamase los ntawm iodine decolorization, thiab paub tseeb hais tias cov blocking nyhuv ntawm PBP2a qhia los ntawm Western-blot tshwm sim, thiab rov qab rhiab heev ntawm MRSA rau -lactam tshuaj tua kab mob [43].

4 Cov ntsiab lus thiab Outlook
Vim yog kev siv tsis tsim nyog lossis kev tsim txom ntawm cov tshuaj tua kab mob, cov kab mob tiv thaiv tau nce zuj zus, uas ua rau muaj kev hem thawj rau tib neeg thiab tsiaj txhu. Cov nroj tsuag rho tawm, xws li terpenes, alkaloids, flavonoids, thiab lwm yam, uas tam sim no tau tshaj tawm tias muaj cov kab mob tua kab mob, muaj cov kab mob tua kab mob zoo, txo cov kab mob, ncua lossis txawm tias rov qab cov kab mob, tab sis thaum siv ib leeg, cov tshuaj tua kab mob ntev ntev. , qhov ntau npaum li cas yog loj, thiab nws tseem nyob rau theem pib ntawm kev tshawb fawb. Txhawm rau tiv thaiv thiab tswj cov kab mob kom zoo dua qub thiab txhim kho kev ua tau zoo, kev tshawb fawb ua ke nrog cov tshuaj tua kab mob yuav tsum tau ua kom muaj zog, qhov ntau npaum ntawm cov nroj tsuag rho tawm thiab tshuaj tua kab mob yuav tsum raug txo kom tsawg, cov tshuaj lom neeg tshwm sim los ntawm kev siv tshuaj loj loj yuav tsum raug txo kom tsawg. txo qis, qhov rhiab heev ntawm cov kab mob rau cov tshuaj tua kab mob yuav tsum raug txo, thiab tiam ntawm cov kab mob resistant yuav tsum tau qeeb los ntawm kev txo cov kab mob tua kab mob.
Nroj tsuag extracts txhim khu lub rhiab heev ntawm cov kab mob rau cov tshuaj tua kab mob los ntawm inhibiting cov kev ua ntawm tshuaj tua kab mob hydrolysis / hloov enzymes, hloov kho cov hom phiaj tshuaj tua kab mob, inhibiting lub efflux twj tso kua mis efflux, nce membrane permeability, thiab inhibiting / clearing biofilms, muab ib tug muaj peev xwm lub tswv yim los txo cov kab mob. Txawm hais tias kev sib xyaw ntawm cov nroj tsuag rho tawm thiab cov tshuaj tua kab mob tau pom tias muaj txiaj ntsig zoo ntawm kev siv tshuaj tua kab mob hauv ntau cov kev tshawb fawb tam sim no, nws tau ua tsis tiav qhov xav tau cov tshuaj tua kab mob hauv cov kev tshawb fawb tom ntej, uas feem ntau cuam tshuam rau kev vam khom nyob rau hauv vitro sim kev tshawb fawb thiab tsiaj sim qauv. Yog li ntawd, kev tshawb nrhiav qhov tob hauv vivo antibacterial mechanism ntawm cov nroj tsuag rho tawm thiab ua ke nrog ntau yam kev soj ntsuam kuaj mob tseem yog lub hom phiaj ntawm kev tshawb fawb yav tom ntej, txhawm rau tshuaj xyuas thiab tsim cov tshuaj sib xyaw ua ke tshiab thiab siv tau zoo los kov yeej qhov tsis xws tam sim no ntawm kev siv ua ke. ntawm cov nroj tsuag extracts thiab tshuaj tua kab mob.
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