Alternatives Therapeutic Approaches To Conventional Antibiotics: Advantages, Limitations and Potential Application in Medicine Ⅱ

4. Antimicrobial Peptides

Nyob rau hauv xyoo tas los no, kev sib kis thiab kev sib kis tau pom tias kev noj qab haus huv pej xeem yuav raug hem thoob ntiaj teb raws likis kab mob, yog li qhov teeb meem no urgently yuav tsum nrhiav lwm txoj rautshuaj tua kab mobuas yog cov tshiab thiab tsis tshua muaj kab mob ua haujlwm. Hauv kev tshawb nrhiav tshiabtshuaj tua kab mob,antimicrobial peptides(AMPs), tseem hu ua tus tswv tsev tiv thaiv peptides, tsis ntev los no tau txais kev txaus siab [146–148]. AMPs yog ib chav kawm ntawm cov peptides me me uas muaj nyob hauv cov xwm txheej thiab yog cov khoom tseem ceeb ntawm lub cev tiv thaiv kab mob ntawm cov kab mob sib txawv. Lawv muaj kev cuam tshuam dav dav rau cov kab mob, fungi, parasites, thiab kab mob. Lawv tau tshawb pom xyoo 1939, tom qab kev tshawb pom ntawm lysozymes hauv xyoo 1922, thaum tus kws kho mob microbiologist Rene Dubos cais cov kab mob Bacillus los ntawm cov av, ib qho tshuaj tua kab mob hu ua gramicidin, uas tau pom tias tiv thaiv nas los ntawm kab mob pneumococcal [149]. Tom qab ntawd, ob peb AMPs tau raug txheeb xyuas hauv ob lub tebchaws prokaryotic thiab eukaryotic [150]. Thawj tus tsiaj AMP tau piav qhia yog defensin, uas tau cais tawm ntawm luav leukocytes [151], tom qab ntawd, lactoferrin tau txheeb xyuas hauv nyuj cov mis nyuj, thiab tib neeg leukocyte lysosomes thiab tib neeg poj niam cev xeeb tub tau pom tias muaj cov AMPs qis-molecular-yuag [152]. Txog rau tam sim no, ntau dua 3000 AMPs tau pom, pom, thiab sau tseg hauv AMP database (APD3) [153]. 

Cov kev tshawb fawb tam sim no tsom rau cov khoom sib xyaw ntuj no ua tshiabtshuaj tiv thaiv kab mobthiab tshiab immunomodulators [148,154], tab sis kuj nyob rau hauv zaub mov, tsiaj txhu, kev ua liaj ua teb, thiab aquaculture. Kev txaus siab rau AMPs tsis ntev los no tau nce ntxiv thaum lub sijhawm mob hnyav ua pa nyuaj ua rau tus mob coronavirus 2 (SARS-CoV-2) kis thoob plaws hauv kev tshawb nrhiav cov tshuaj tiv thaiv kab mob tshiab los tiv thaiv COVID-19 [154]. 

Nyem qhov no kom tau txais cov lus qhia ntxiv txog Cistanche tshuaj ntsuab li

Alternatives Therapeutic Approaches to Pa Tshuaj Tua Kab Mob

4.1. Qhov zoo

Txij li thaum qhov kev tshawb pom ntawm ntuj bioactive AMPs muaj peev xwm nthuav dav ntau yam kab mob, peptide-based therapeutics yog nyob rau hauv kev tshuaj xyuas ntawm cov kws tshawb fawb. AMPs inhibit ntau yam kab mob los ntawm ntau haiv neeg thiab tshwj xeeb mechanisms los ntawm feem ntau tsom cov cell membranes los yog tshwj xeeb intracellular Cheebtsam [155]. AMPs yog cov kws kho mob uas muaj peev xwm ua tau zoo, uas muaj txiaj ntsig zoo rau cov kab mob dav dav. Lawv hu ua "natural antibiotics". Qee cov AMPs tuaj yeem ua rau tuag sai ntawm Gram-positive, thiab Gram-negative, fungi, parasites, encapsulated viruses lossis qog hlwb hauv feeb. AMPs muaj kev pheej hmoo tsawg ntawm kev txhim kho kev tiv thaiv thiab tuaj yeem cuam tshuam cov kab mob tiv thaiv kab mob tiv thaiv kab mob [155]. Lub hauv paus ntsiab lus no tshwm sim los ntawm qhov tseeb tias AMPs feem ntau (tab sis tsis yog ib txwm, raws li tau teev tseg saum toj no) tawm tsam cov lipid tivthaiv ntawm cov ntshav plasma, cov khoom siv ntawm tes uas tau xav tias yuav nyuaj rau hloov pauv hauv nws cov yam ntxwv physicochemical los ntawm microbial lub hom phiaj.

Thaum kawg, AMPs tau pom ntau dua los ua ib qho kev cog lus kho mob rau kev kho mob ntawm cov kab mob biofilm, yog ib qho kev hem thawj loj hauv kev kis kab mob. Tag nrho cov txiaj ntsig no ua rau AMPs cov neeg sib tw zoo tshaj plaws rau kev siv tshuaj. AMPs siv lawv cov tshuaj tiv thaiv kab mob feem ntau los ntawm ob txoj kev sib txawv. Membrane-targeting AMPs hloov cov qauv kev ncaj ncees ntawm cov cell membrane thaum AMPs uas siv cov txheej txheem uas tsis yog-membrane feem ntau cuam tshuam cov synthesis ntawm nucleic acids, cov enzymes tseem ceeb, thiab lwm cov proteins ua haujlwm. Cov proteins tshiab no tuaj yeem yog lub hauv paus ntuj los yog hluavtaws. AMPs los ntawm ntau hom, suav nrog amphibians, kab, tsiaj txhu, thiab ntses, suav txog 75.65 feem pua ​​​​ntawm tag nrho AMPs, thaum cov seem feem ntau yog los ntawm cov nroj tsuag thiab cov kab mob thiab suav txog 13.5 feem pua ​​​​thiab 8.53 feem pua ​​​​ntawm tag nrho AMPs, feem.156]. Cov kab mob AMPs feem ntau hu ua bacteriocins, muaj txiaj ntsig qis dua li AMPs, thiab muaj kev txwv rau ob peb hom. Bacteriocins tso tshuaj tua kab mob thiab inhibit loj microbial cov neeg sib tw [157,158]. Remarkably, tiv thaiv cov tshuaj tua kab mob thiab cov kab mob bacteriocins yog ywj siab thiab tsis muaj kev tiv thaiv kab mob tau sau tseg txog tam sim no [159]. Cov noob uas koom nrog hauv kev tsim cov kab mob bacteriocin yog ib feem ntawm cov noob caj noob ces xws li conjugative transposons (nisin) thiab plasmids (lactococci 972) [160]. Qhov no pab txhawb lawv txoj kev nthuav tawm thiab piav qhia, piv txwv li, muaj peev xwm ntawmP. pentosaceusthiabLactobacilluslos ua ke PA1/AcH kwv yees [161]. Nws tuaj yeem txiav txim siab tias cov kab mob bacteriocins yog qhov kev xav tshiab los daws qhov teeb meem tiv thaiv yog tias cov txheej txheem kev ua haujlwm ntawm cov molecules thiab lawv cov degradation tau nkag siab zoo. Nyob rau hauv lem, lub marine ib puag ncig yog paub tias yog ib tug ntawm cov richest qhov chaw ntawm AMPs, nrog rau cov dej hiav txwv uas npog tsuas yog 70 feem pua ​​ntawm lub ntiaj teb. Tsis zoo li thaj chaw hauv av, lawv hloov tau ntau dua rau qhov hnyav ib puag ncig, xws li salinity siab [156,162]. Cov nroj tsuag tau txais los ntawm AMPs yog peptides uas pom muaj zog thiab dav-spectrum antimicrobial kev ua haujlwm. Ntxiv rau qhov muaj zog microbicidal kev ua haujlwm ntawm cov nroj tsuag AMPs tiv thaiv kab mob, kab mob, fungi, parasites, thiab protozoa, lawv kuj muaj kev tiv thaiv kab tawm tsam oomycetes thiab herbivore pests, thiab anticancer tiv thaiv qee cov qog nqaij hlav cancer [155,156,162,163]. Hais txog kab AMPs, lawv ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv kab mob humoral. Kab AMPs yog synthesized nyob rau hauv lub cev rog ntawm kab thiab khaws cia nyob rau hauv lub hemolymph [164]. Ntau tshaj 200 AMPs tau txheeb xyuas cov kab rau hnub no

Txawm hais tias muaj ntau yam zoo ntawm AMPs tau muab rho tawm los ntawm cov khoom siv ntuj tsim, lawv muaj ntau qhov tsis zoo, nrog rau kev ruaj ntseg tsis zoo, kev tiv thaiv ntsev, thiab cov tshuaj lom neeg siab, uas cuam tshuam rau lawv txoj kev siv dav dav, yog li qhov tshwm sim ntawm hluavtaws AMPs. Ntau txoj hauv kev tau tsim los tsim cov AMPs tshiab los ntawm kev hloov kho cov kab ke ntawm AMPs ib txwm muaj nyob hauv ntau yam kab mob. Nws tau pom tias kev hloov pauv me me hauv cov amino acid muaj pes tsawg leeg tuaj yeem ua rau muaj kev hloov pauv hauv txhua qhov kev sib haum xeeb thiab lub cev muaj zog ntawm peptide [165]. Tag nrho cov nyob rau hauv tag nrho, cov AMPs no muaj kev nyab xeeb, tsis muaj los yog tsawg dua cov tshuaj lom, thiab nyuaj rau induce kab mob tshuaj tiv thaiv piv rau cov pa tshuaj tua kab mob [166]. 

4.2. Cov ntawv thov hauv Tshuaj

AMPs yog cov neeg ua haujlwm ntau yam uas muaj ntau yam kev kho mob xws li tshuaj tiv thaiv kab mob, immunomodulatory, endotoxin neutralization kev ua ub no, thiab cytotoxic cuam tshuam rau cov qog nqaij hlav cancer, ua rau lawv cov neeg sib tw zoo rau kev coj noj coj ua, ntxiv rau lawv cov tshuaj tiv thaiv kab mob ncaj qha [167,168]. Kev ua ub ua no nrawm thiab dav dav, siv ntau yam txuj ci, thiab tsis tshua muaj peev xwm rau kev txhim kho kev tiv thaiv ntawm AMPs yog lub hauv paus tseem ceeb ua rau lawv nyiam nyob rau hauv kev lag luam biopharmaceutical thiab peev hauv kev lag luam tshuaj tua kab mob peptide. Ntau qhov kev tshawb fawb tau qhia txog qhov cuam tshuam ntawm nisin hauv kev kho mob ntawm ntau yam kab mob, xws li mastitis, qhov ncauj, ua pa, thiab tawv nqaij [148,152,169]. Mastitis yog ib hom kab mob o nyob rau hauv cov poj niam lactating uas ua rau lub cev tsis ua haujlwm ntawm lactation [170]. Staphylococcus aureusthiabStaphylococcus epidermidisyog ob hom kab mob uas ua rau muaj kab mob mastitis [170]. Cov peptide nisin ua rau inhibition ntawm cov kab mob loj hlob los ntawm kev tsim ntawm daim nyias nyias pores thiab los ntawm kev cuam tshuam cov phab ntsa ntawm tes biosynthesis los ntawm kev sib cuam tshuam ntawm lipid II.171]. Lwm qhov piv txwv ntawm cov kab mob kis tau los ntawm AMPs siv kho mob los ua lwm txoj hauv kev tshuaj tua kab mob yog gramicidin, uas yog sib xyaw ntawm gramicidin A, B, thiab C. Cov no yog AMPs ib txwm tsim los ntawmBrevibacillus brevis, nrog kev ua haujlwm tawm tsam ntau tus kab mob Gram-zoo, inducing membrane depolarization thiab thiaj li cell lysis [152,172,173]. Gramicidin yog ib feem ntawm Neosporin®, triple tshuaj tua kab mob siv nyob rau hauv ophthalmic thiab tshuaj pleev ib ce [152]. Nws tau raug pom zoo thiab ua lag luam raws li anionic AMP rau kev kho mob ntawm daim tawv nqaij kab mob los ntawm Gram-zoo kab mob [174]. Ib txoj kev tshawb fawb tsis ntev los no tau pom tias kev kho ua ntej nrog Tachyplesin III ntawm nas tiv thaiv lawvPseudomonas aeruginosathiabAcinetobacter baumanniikev kis kab mob, txo qhov tsim cov cytokines pro-inflammatory (IL-1 , IL-6, and TNF- ) thiab induces macrophage phagocytosis, qhov tseem ceeb rau kev tshem tawm cov kab mob hauv cov koob tshuaj raws li [152,175]. Tag nrho cov kev tshawb pom no yuav tsum tau lees paub hauv tib neeg kev sim tshuaj. Muab ntau yam ntawm AMPs uas muaj nyob rau hauv cov xwm txheej, nws xav tias lwm cov tshuaj tshiab tshuaj peptides tshwm sim los ntawm xwm yuav nrhiav tau cov ntaub ntawv kho mob yav tom ntej.

4.3. Kev txwv

Txawm hais tias AMPs muaj ntau yam txiaj ntsig, tsuas yog peb AMPs tau pom zoo los ntawm US FDA rau kev siv tshuaj kho mob, xws li, gramicidin, colistin, thiab daptomycin [176]. Gramicidin yog nquag tawm tsam ntau yam kab mob Gram-positive thiab Gram-negative kab mob, txawm hais tias nws cov tshuaj lom neeg hnyav rau tib neeg erythrocytes muaj cov tshuaj kho mob txwv rau cov tshuaj pleev ib ce. Polymyxin thiab colistin, uas yog cationic peptides uas tau siv rau ntau xyoo lawm, tau pom muaj kev txaus siab nyob rau lub sijhawm tsis ntev los no vim lawv muaj zog tiv thaiv MDR Gram-negative pathogens. Lawv lub peev xwm los khi cov lipid Ib feem ntawm LPS ua rau lawv muaj txiaj ntsig riam phom, cov peev txheej kawg los tawm tsam septic shock, txawm hais tias lawv paub nephrotoxicity. Txawm li cas los xij, kev tawm tsam tau tshwm sim thiab nthuav tawm ntawm qhov ceeb toom, ua rau muaj kev cuam tshuam rau kev ua haujlwm ntawm cov tshuaj muaj txiaj ntsig zoo. Raws li rau daptomycin, qhov membrane-bound cyclic lipopeptide tau muab lub teeb ntsuab los ntawm FDA hauv xyoo 2003 los kho cov kab mob Gram-zoo. Nyob rau xyoo tas los no,Staphylococcus aureuskev tawm tsam tau raug tshaj tawm ntau ntxiv thiab kev tshawb nrhiav kev hloov pauv uas tuaj yeem txuas ntxiv kev kho mob siv cov tshuaj tua kab mob tseem ceeb no tab tom ua haujlwm. Ntxiv nrog rau AMP kev tiv thaiv tau piav qhia saum toj no, muaj ib theem ntawm qhov nyuaj ntawm kev nqa cov molecules no mus rau kev ua lag luam, txawm tias siv tshuaj pleev los yog kev kho mob. Polyphor's theem 3 kev soj ntsuam kev soj ntsuam ntawm kev nyab xeeb thiab kev ua tau zoo ntawm cov hlab ntsha murepavadin tau raug tso tseg ntxov vim qhov nce qib creatinine hauv cov neeg mob AMP-kho, qhia tias lub raum tsis ua haujlwm [177]. 

5. Nanoparticles

Thawj cov cim ntawm kev siv nanoparticles los ntawm noob neej hnub rov qab mus rau Mayan lub teb chaws Ottoman (hauv 800 BC), lawv tau siv cov xim xiav tuaj yeem tiv taus huab cua los ntawm kev sib xyaw ntawm nanoporous av nplaum thiab cov xim muaj hlau nanoparticles [178]. Kev tsim cov nanoparticles tau yog ib qho kev loj hlob sai rau kev siv biomedical, tshwj xeeb tshaj yog nyob rau hauv kev kho mob ntawm cov qog thiab lawv cov kev kuaj mob, txij li thaum pib ntawm 1970s thiab exponentially txij li thaum 2000s [179]. Cov khoom nano-cov khoom zoo tshaj plaws (optical, lub cev, thermal, tshuaj, thiab lwm yam) pab kom lawv siv raws li vectors, nrog rau kev kuaj mob thiab kho cov laj thawj. Nanotechnologies mob siab rau kev siv kho mob tau txhais hnub no raws li lo lus "nanomedicine". Cov nanoparticles nrog cov tshuaj tiv thaiv kab mob yog cov inorganic hais ntawm nanometric loj. Lawv tuaj yeem tua cov kab mob ntawm cov kab mob lossis cov poov xab thiab nkag mus rau cov kab mob no kom cuam tshuam nrog lub hom phiaj tshwj xeeb tab sis kuj ua rau muaj cov dawb radicals. Qhov tseem ceeb tshaj, ntau yam thiab cov txheej txheem tshwj xeeb ntawm kev ua ntawm nanoparticles ua rau nws tsis zoo li cov kab mob tuaj yeem txhim kho kev tiv thaiv thiab tuaj yeem pab txo qis kev kub ntxhov thoob ntiaj teb ntawm cov kab mob tshwm sim [179,180]. 

5.1. Qhov zoo

Nanomedicine yog kev xa tshuaj siv nano vectors tso cai rau kev thauj mus los thiab tso tawm cov khoom muaj txiaj ntsig ntawm nws lub hom phiaj tshuaj. Txoj hauv kev no, yog li ntawd, ua kom cov tshuaj ua kom zoo dua qub thiab txwv lawv cov kev cuam tshuam tsis zoo los ntawm kev hloov kho txoj hauv kev pharmacokinetic thiab bioavailability [181]. Cov tshuaj tua kab mob tshwj xeeb muaj nyob hauv cov hlau nanoparticles (MNPs) ua los ntawm cov nyiaj, kub, zinc oxide, thiab titanium oxide. Lawv cov tshuaj muaj pes tsawg leeg ua rau muaj kev sib txuas ntev dua, lub hom phiaj tseem ceeb ntawm cov tshuaj tua kab mob nrog rau kev ua haujlwm saum npoo av ntawm lub hom phiaj qhov chaw, thiab tiv thaiv cov enzyme degradation [182]. Qhov nthuav tshaj plaws yog tias lawv tuaj yeem xa cov tshuaj tua kab mob hauv cov kab mob hauv lub cev uas cov kab mob nyob. Yog li, lawv txhim kho tshuaj stabilization, nce cov tshuaj ncig thiab muab kev txhim kho kev xa khoom ntawm lub hom phiaj thiab kev kho mob ntau dua. Nyob rau tib lub sijhawm, lawv txo cov toxicity thiab cov kev mob tshwm sim, nce cov kab mob tua kab mob, thiab txo cov tshuaj uas xav tau thiab txawm tias lub sijhawm kho mob [183,184]. Tag nrho cov txiaj ntsig no ua rau lawv siv cov tswv yim zoo tshaj plaws los kov yeej cov tshuaj tua kab mob tsis zoo [185]. 

5.2. Cov ntawv thov hauv Tshuaj

Nanobiotics yog cov tshuaj tua kab mob tom ntej thiab tuaj yeem siv los ua tshuajtiv thaiv kab mob nrog cov kab mob hauv cov kab mob feem ntau. Antibacterial thaj chawntawm noble hlau (tsuas yog tooj liab thiab nyiaj) tau paub ntev thiab siv nyob rau hauv lub neej txhua hnub. Piv txwv li, qee lub tsev kho mob tau nruab lawv lub qhov rooj nrog cov tooj liab txheej txhawm rau txhawm rau txwv kev kis kab mob hauv tsev kho mob ib puag ncig [186]. Kev tshawb fawb ntawm nanoparticles tau pom nyob rau hauv vitro antimicrobial kev ua si tiv thaiv MDR kab mob, suav nrog ESKAPE kab mob (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosathiabEnterobacter) [180,187–189]. Qhov tseeb, ib txoj kev tshawb fawb pom tseeb tau tsim cov koob tshuaj tiv thaiv kab mob ntawm cov nyiaj nanoparticles tawm tsam enterobacteria xws liEscherichia colilos yogKlebsiella pneumoniaenrog ib qho kev hwm MIC txog 1.4µg / mL, nrog rau cov tshuaj tua kab mob ntawm gentamicin, cefotaxime, thiab meropenem ntawm cov tsiaj no tau nce ntxiv nyob rau tib lub sijhawm muaj cov nyiaj nanoparticles [190]. Lwm cov kev tshawb fawb tau pom ob qho tib si hauv vitro thiab hauv vivo kev ua tau zoo tiv thaiv kab mob Gram-positive thiab Gram-negative [191,192]. Tsis tas li ntawd, nws tuaj yeem yog lwm txoj hauv kev kho mob tuberculosis, uas yog qhov teeb meem kev noj qab haus huv tseem ceeb kis rau ntau lab tus tib neeg thoob ntiaj teb. Kev siv cov tshuaj thib ib tsis raug tuaj yeem ua rau MDR tuberculosis, uas tom qab ntawd kho nrog tshuaj khomob lossis tshuaj thib ob xws li ethionamide (ETH). Txawm li cas los xij, cov neeg mob feem ntau pom tias nws nyuaj rau kev ua raws li cov kev kho mob uas yuav tsum tau txhaj tshuaj ETH ntau. Cov nanoparticles tuaj yeem encapsulate cov tshuaj sib xyaw ua ke, uas yuav yooj yim rau kev kho mob thiab ua kom cov neeg mob ua raws li [181]. Thaum kawg, tag nrho cov kev tshawb fawb no tseem nyob ntawm qhov kev sim ntsuas, hauv vitro lossis hauv vivo siv cov qauv tsiaj. Kev txhais lus kho mob yuav tsum muaj kev nkag siab zoo txog cov tshuaj pharmacokinetics thiab pharmacodynamics ntawm NPs thiab kev ntsuam xyuas ntawm lawv cov tshuaj lom ntawm cov cellular thiab cov kab ke [180]. Yog li ntawd, cov hlau nanobiotics tau pom tias muaj txiaj ntsig zoo dua li cov tshuaj tua kab mob ib leeg vim lawv qhov kev ruaj ntseg ntawm cov kab mob tshwm sim los ntawm cov kab mob intracellular [193–195]. Hauv kev xyaum, nan obiotics yuav muab cov tshuaj xa mus rau lub cev, qhov ncauj, transdermal, lossis lwm yam kev siv, kev hnav khaub ncaws zoo dua cov kab mob, cov khoom siv kho mob zoo tshaj plaws thiab cov tshuaj tiv thaiv kab mob zoo dua ntxiv [193].

5.3. Kev sib xyaw ua ke

Kev kho mobCov nanoparticles tuaj yeem ua ke rau cov tshuaj tua kab mob (cov tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tua kab mob). Kev sib xyaw nrog cov tshuaj tua kab mob molecules yog cov ntaub ntawv tshaj plaws, thiab lawv hu ua nanobiotics [196]. Cov MNPs yog siv rau lawv cov nqi txo, yooj yim synthesis thiab siv [193]. MNPs yog raws li ntau hom hlau: feem ntau kub (Au), nyiaj (Ag), tooj liab oxide (CuO), hlau oxide (Fe.3O4 los yog Fe2O3), titanium dioxide (TiO2), thiab zinc oxide (ZnO) [193]. Silver nanoparticles (AgNPs) yog siv tsis tau tsuas yog nyob rau hauv kev tshawb fawb soj ntsuam tab sis kuj nyob rau hauv tib neeg thiab veterinary teb vim lawv catalytic, tshwj xeeb kho qhov muag thiab lom zog. Kub nanoparticles (AuNPs) cov txiaj ntsig tseem ceeb yog lawv cov khoom siv yooj yim thiab kev hloov kho los ntawm ib lossis ntau cov tshuaj sib txawv ntawm thiol ligands thiab lawv raug suav tias yog MNP tshuaj lom tsawg tshaj plaws.182]. Txij li thaum MNPs ua haujlwm raws li cov neeg nqa tshuaj, lawv ua kom yooj yim rau cov tshuaj tua kab mob thauj mus rau ntawm lub xov tooj ntawm tes. Qhov kev sib cuam tshuam ntawm nanoparticles thiab cov tshuaj tua kab mob no ua rau muaj cov tshuaj tiv thaiv kab mob ntawm cov chaw tshwj xeeb ntawm cov cell membrane. Tshwj xeeb, kev sib cuag nrog cov hlwb tau txhim kho thiab permeability ntawm daim nyias nyias yog nce los ntawm AgNPs 'thiab AuNPs 'affinity rau sulfur-muaj proteins ntawm cov kab mob cell membranes. Qhov no ua rau nws yooj yim dua rau cov tshuaj tua kab mob nkag mus rau hauv lub cell [194].

5.4. Kev txwv

Nanoparticles sawv cev rau kev pheej hmoo rau tib neeg kev noj qab haus huv txawm tias lawv cov khoom zoo thiab ntau yam kev siv. Kev tshawb fawb hauv vitro thiab hauv vivo tau pom tias MNPs tuaj yeem nkag mus rau hauv cov hlwb thiab ua rau oxidative kev nyuaj siab, o, DNA puas, thiab cov kab mob toxicity, uas txwv tsis pub lawv siv [197,198]. Lub luag haujlwm tseem ceeb ntawm MNPs lub luag haujlwm rau lawv cov txiaj ntsig toxicological tau raug ntaus nqi rau:• Qhov loj me, vim lawv qhov nrawm nrawm rau hauv tib neeg lub hlwb thiab lawv lub peev xwm hla hla cov hlab ntsha-hlwb barrier (200 nm). NPs qis dua 10 nm feem ntau pom muaj ntau yam tshuaj tua kab mob tab sis kuj muaj cytotoxicity siab;Agglomeration, uas pab nyob rau hauv cov txheej txheem sedimentation thiab slows NP diffusion uas ua rau kom zoo npaum li cas;

• Kev them nqi nto, txhawm rau tswj cov protein khi rau NPs, cellular uptake, oxidative stress, autophagy, o, thiab apoptosis, NPs tus nqi yog qhov tseem ceeb (them NPs tau pom tias muaj cytotoxic ntau dua li cov qauv nruab nrab, thiab NPs tau zoo dua. cytotoxic tshaj qhov tsis zoo sib txawv ntawm qhov loj me). Tam sim no, MNPs tuaj yeem tsim los txo lawv cov tshuaj lom rau tib neeg [199]. Qhov loj tuaj yeem raug kho kom haum rau qhov ua tau zoo, thiab cov neeg ua haujlwm capping tuaj yeem siv los tiv thaiv agglomeration, tsis txhob xav tau nanoparticle oxidation thiab txhim kho ion tso tawm. Feem ntau siv capping agents yog oleic acid, polyacrylic acid, polyethylene glycol (PEG), polyvinyl cawv (PVA), thiab polyvinylpyrrolidone (PVP) [200,201].

6. Cov roj tseem ceeb

Cov khoom ntuj tsim, xws li cov nroj tsuag tshuaj, cov roj yam tseem ceeb (EOs), thiab cov tshuaj ntsuab tau suav hais tias yog cov neeg ua haujlwm cog lus. EOs yog ib qho ntawm cov khoom lag luam uas muaj txiaj ntsig zoo tshaj plaws los ntawm cov nroj tsuag, ua ntau lub luag haujlwm rau ntau yam kev txhawb nqa kev noj qab haus huv [202,203]. EOs yog tsim los ntawm MAP raws li cov metabolites theem nrab thiab yog cov sib xyaw ua ke uas muaj ntau yam sib xyaw ntawm ntau qhov sib txawv [204]. Tam sim no, tshaj 3000 EOs paub, 10 feem pua ​​​​ntawm cov lag luam thiab kev lag luam cuam tshuam. Cov khoom no muaj peev xwm reservoirs ntawm ntau bioactive tebchaw nrog ntau yam khoom muaj txiaj ntsig, thiab lawv tau ua raws li cov neeg siv khoom nyiam tam sim no rau cov khoom ntuj. Lawv kuj muab qhov zoo dua ntawm kev zam rau tib neeg lub cev nrog tsawg dua kev phiv [205,206]. 

6.1. Kev siv ntawm EOs

Hauv qhov xwm txheej, EOs ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv cov nroj tsuag, los ntawm kev ua cov tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tua kab mob, thiab tshuaj tua kab, thiab tseem tiv thaiv herbivores los ntawm kev txo lawv txoj kev noj qab haus huv rau cov nroj tsuag. Lawv kuj tuaj yeem nyiam cov kab kom nyiam qhov tawg ntawm paj ntoos thiab cov noob los yog tawm tsam lwm tus uas tsis xav tau. Vim lawv cov kab mob bactericidal thiab fungicidal, lawv kuj tau siv los ua lwm yam khoom siv tshuaj hluavtaws los tiv thaiv ecological equilibrium yam tsis muaj kev cuam tshuam tib yam thib ob [207,208]. EOs tau siv rau ntau tshaj 5000 xyoo hauv ntau haiv neeg thiab rau ntau lub hom phiaj sib txawv, suav nrog kev tu tus kheej (ntaus thiab tshuaj pleev ib ce), khoom noj khoom haus, kev saib xyuas hauv tsev, tshuaj tua kab mob rau tib neeg thiab tsiaj txhu (cov tsiaj txhu thiab tsiaj hauv tsev), thiab cov neeg saib xyuas kev noj qab haus huv rau kev kho mob ntawm ntau yam kab mob [203,209–211]. EOs feem ntau paub txog kev siv tshuaj ntau yam tshuaj, xws li tshuaj tiv thaiv kab mob (lavender, sage), anticancer (salvia), anti-inflammatory (eucalyptus, lavender), analgesic (lavender), anxiolytic (feem ntau fennel), antidepressant (citron) immunomodulatory ( eucalyptus) tshuaj tua kab mob (clove, cumin, thyme, oregano), tshuaj tua kab mob (Curcuma, lavender, eucalyptus), tshuaj tua kab mob (eugenol, eucalyptus, qhiav nyom, clove), insecticidal (artemisia, eucalyptus, lavender), thiab antioxidant kev ua haujlwm (coriander). , ib) [206,212–214]. Tsis tas li ntawd, EOs tuaj yeem siv los ua lwm yam tshuaj tua kab mob txhawm rau ua kom lub neej txee ntawm cov nplej thiab cov qoob loo thiab hauv kev nyab xeeb zaub mov [215]. Yog li, cov muaj pes tsawg leeg thiab cov khoom siv tshuaj ntawm EOs yog cov ncauj lus txuas ntxiv ntawm kev tshawb fawb dav dav.

6.2. Antimicrobial nyhuv ntawm EOs

EOs thiab lawv cov khoom tseem ceeb tau ua pov thawj tias muaj txiaj ntsig zoo los tswj kev sib kis ntawm qee yam kab mob. Cov tshuaj tua kab mob ntawm EOs tau paub ntev ntev thiab niaj hnub no muaj ntau cov ntawv tshaj tawm tseem ceeb tau lees paub tias lawv cov kab mob bacteriostatic thiab cov kab mob bactericidal tawm tsam cov kab mob pathogenic, txawm tias tsawg heev [216,217]. Ntau cov molecules tam sim no hauv EOs tau txais txiaj ntsig los ntawm cov khoom siv tshuaj tua kab mob, tshwj xeeb tshaj yog phenols (xws li carvacrol, thymol thiab eugenol), cawv (xws li linalool), thiab aldehydes (xws li cinnamaldehyde). Cov tshuaj tua kab mob yog cuam tshuam los ntawm ntau yam xws li tshuaj lom neeg muaj pes tsawg leeg ntawm EO kuaj, txoj kev sim siv, thiab kuaj kab mob. Lawv cov tshuaj tua kab mobnyob ntawm qhov concentration ntawm cov ntsiab lus tseem ceeb, cov teebmeem kev sib koom ua ke, thiab / lossis cov khoom ntxiv thiab cov khoom me me tam sim no [218,219]. Cov khoom siv bioactive ntawm EOs muaj cov tshuaj tua kab mob tshwj xeeb; Piv txwv li, kev puas tsuaj ntawm tes ntawm cov kab mob yog tshwm sim los ntawm lub peev xwm ntawm cov tebchaw los cuam tshuam cov kab mob hauv lub cell membrane, uas ua rau muaj kev hloov pauv hauv cell morphology, hloov pauv hauv daim nyias nyias permeability thiab to ntawm electrolytes. Piv txwv li, thymol, carvacrol thiab eugenol (feem ntau phenolic tebchaw ntawm ob peb EOs) tuaj yeem ua rau cov kua qaub C16 thiab C18 saturated fatty acids thiab txo cov C18 unsaturated fatty acids. Qhov kev txiav txim ntawm EOs tsis txwv rau fatty acids lawv tus kheej tab sis kuj tuaj yeem cuam tshuam cov enzymes lub luag haujlwm rau lawv cov biosynthesis. Piv txwv li, qee qhov kev tshawb fawb tau pom tias qee qhov EOs cuam tshuam los ntawm cov txheej txheem sib txawv (kev sib tw, tsis sib tw thiab tsis sib tw) [213,220]. Qhov sib txawv ntawm EOs tuaj yeem ua rau cov proteins uas muaj nyob hauv cov kab mob thiab cuam tshuam rau kev faib cell. Tsis tas li ntawd, lawv tuaj yeem txo tus nqi ntawm ATP ntau lawm thiab ua rau muaj kev cuam tshuam hauv cov kab mob ua pa. Qee qhov EOs muaj kev nqis tes ua ntawm pawg neeg paub, siv los ntawm cov kab mob los tswj hwm thiab xyuas kom muaj kev sib txuas lus ntawm lawv [221,222]. Ntau qhov kev tshawb fawb tau tshawb xyuas qhov sib koom ua ke ntawm EOs cov khoom [223,224]. Ib qho kev sib txawv ntawm cov txiaj ntsig sib txawv tau pom raws li kev kuaj kab mob, tshuaj tua kab mob thiab cov roj tseem ceeb tau sim [225]. Kev sib xyaw ua ke ntawm ob cov tshuaj tiv thaiv kab mob ua rau muaj kev cuam tshuam tsis zoo, tsis txaus ntseeg, lossis kev sib koom ua ke, nyob ntawm cov txheej txheem los ntawm txhua tus neeg sawv cev tiv thaiv kab mob, cov yam ntxwv ntawm cov kab mob kuaj kab mob, thiab kev sib cuam tshuam ntawm cov tshuaj tiv thaiv kab mob sib kis ntawm ob tus kab mob antimicrobial [226]. 

6.3. Kev txwv

Txawm hais tias yog cov khoom siv ntuj tsim thiab lawv cov kev siv tshuaj kho mob, qee qhov EOs tau tshaj tawm tias yuav ua rau muaj kev phiv xws li lom, mob hawb pob, tiv tauj dermatitis, mob taub hau, nce los ntshav, qhov muag khaus, neurotoxicity, genotoxicity, thiab immunotoxicity. Feem ntau ntawm EOs, nyob rau hauv cov koob tshuaj ntau txaus, yuav ua rau muaj tshuaj lom. Tsis tas li ntawd, cov tshuaj lom yuav tshwm sim tom qab noj los yog raug dermal. Ntau EOs, suav nrog lavender,Npeta cataria(catnip), thiabMelissa Officinalis(txiv qaub balm), tau raug soj ntsuam nrog cov kev ntsuam xyuas qhia tau hais tias EOs qhia toxicity ntawm tsawg concentrations. Nws yuav tsum tau hais tias ib qho ntawm cov txheej txheem tseem ceeb ntawm cytotoxicity yog membrane puas, zoo ib yam li pom hauv cov kab mob thiab cov poov xab [226–228]. EOs kuj tseem muaj cov sib xyaw ua ke uas muaj cov duab zoo nkauj heev thiab muaj kev cuam tshuam rau degradation. Qhov no yuav tsum muaj kev cia zoo dua los tiv thaiv cov roj tiv thaiv kom tsis txhob txo qis thiab pab tswj cov roj yam tseem ceeb uas muaj qhov tsawg kawg nkaus. Lwm qhov kev sib tw rau kev siv lub ntsiab lus ntawm EOs los ntawm cov kev lag luam uas cuam tshuam yog lawv cov kev tswj kom zoo, nrog rau cov ntawv cai lij choj hais txog lawv cov ntawv thov [228]. 

7. Antisense Antimicrobial Therapeutics

Antisense therapeutics yog ib daim ntawv biotechnological-raws li kev kho tshuaj tua kab mob siv tshuaj analogs ntawm luv luv, ib leeg-stranded oligomers uas ua raws li cov qauv ntawm RNA lossis DNA thiab khi rau qhov tshwj xeeb, ntxiv RNA hauv lub hom phiaj kab mob. Antisense antimicrobial kev kho mob yog li ntawd ua los ntawm kev ntsiag to kev qhia ntawm cov noob tshwj xeeb [229]. Antisense thev naus laus zis tau tsim los rau ntau xyoo los tawm tsam cov kab mob cab, kab mob thiab kab mob. Antisense thev naus laus zis tau siv los ua cov tshuaj tua kab mob thiab lawv tau raug sim tawm tsam feem ntau MDR cov chaw kho mob cais nrog rau carbapenem-resistant.Escherichia coli, ncua-spectrum beta-lactamaseKlebsiella pneumoniae, New Delhi metallo-beta lactamase -1 nqaKlebsiella pneumoniae, thiab MDRSalmonella enterica. Hauv kev tshuaj xyuas no, peb yuav tsom mus rau kev kho oligonucleotide raws li txoj hauv kev kom txo tau cov kab mob tsis zoo rau kev kho tshuaj tua kab mob [230].

7.1. Mechanism ntawm Action

Yeej, lub luag haujlwm tseem ceeb ntawm cov tshuaj tua kab mob yog txhawm rau tiv thaiv kev loj hlob thiab / lossisKev muaj peev xwm ntawm cov kab mob los ntawm kev tsom mus rau kev txuag xws li DNA replication, cell phab ntsasynthesis, protein synthesis, thiab metabolism. Contrariwise, los ntawm kev siv antisense thev naus laus zis ua cov tshuaj tua kab mob hauv cov kab mob, cov tshuaj tiv thaiv kab mob khi rau cov hom phiaj mRNA thiab kev txhais lus ntsiag to lossis txhawb kev degradation ntawm lub hom phiaj mRNA. Ob peb lub oligonucleotide-raws li platforms tau tsim, ob txoj hauv kev tseem ceeb rau kev hais lus ntawm cov noob muaj xws li antisense oligonucleotides thiab luv-interfering RNAs. Ob leeg muaj kev sib txuas ntxiv rau lawv lub hom phiaj mRNA. Hybridization ntawm oligonucleotide inhibits kev txhais ntawm cov noob sib raug ntawm kev degradation ntawm lub hom phiaj mRNA los yog kev cuam tshuam ntawm ribosomal binding [229,231–233]. Tam sim no, cov qauv tshuaj tseem ceeb uas tau tsim los rau kev siv tshuaj tua kab mob muaj xws li phosphorothioates, xauv nucleic acids, peptide nucleic acids, thiab phosphorodiamidate morpholino oligomers [229,233]. Qhov kev txhawj xeeb tseem ceeb tshaj plaws rau kev kho tshuaj tiv thaiv kab mob yog kev xa khoom ntawm cov khoom siv tshuaj tua kab mob oligomers rau hauv cov kab mob cytoplasm uas yuav tsum tau txuas ntawm lwm qhov sib txuas uas tuaj yeem nkag mus rau cov kab mob ntawm phab ntsa. Cov kev tshawb fawb tsis ntev los no tau siv cov tshuaj antisense oligomers ua ke los ntawm cov xov tooj ntawm tes-peptides los yog ib qho kev sib txuas ntawm cationic thiab non-polar amino acids vim hais tias cov phab ntsa ntawm tes ntawm cov kab mob yog ze li impenetrable los ntawm siab molecular hnyav oligomers [229,234,235].

7.2. Kev ua tau zoo

Thaum Lub Ob Hlis 2017, WHO tau tshaj tawm nws thawj daim ntawv teev cov tshuaj tua kab mob-tiv taus "cov kab mob tseem ceeb" - ib phau ntawv ntawm 12 tsev neeg ntawm cov kab mob uas ua rau muaj kev hem thawj loj tshaj plaws rau tib neeg kev noj qab haus huv [236]. Cov kab mob no tau dhau los ua cov tshuaj tua kab mob ntau, suav nrog carbapenems thiab thib peb tiam cephalosporins [5]. Raws li kev daws teeb meem, antisense therapeutics muab lub peev xwm rau gene sequence-specific therapies uas tuaj yeem tsom mus rau ntau txoj hauv kev hauv cov kab mob, tsim kom sai, thiab hloov kho ntau dua li cov tshuaj tua kab mob molecule [237]. Antisense oligonucleotides thiab cuam tshuam luv luv RNAs yog lwm txoj hauv kev los tsim cov noob tshwj xeeb oligomers uas tuaj yeem tsom rau ib qho kab mob. Txoj hauv kev tshiab no yuav luag tshem tawm lossis txo qis lub sijhawm xav tau rau kev tshawb pom ntawm cov kab mob tshiab thiab nthuav dav ntau yam ntawm cov hom phiaj muaj peev xwm rau txhua tus noob uas muaj lub hauv paus paub hauv cov kab mob [229].

7.3. Cov ntawv thov hauv Tshuaj

Extended-spectrum -lactamase ntau lawm yog ib qho ntawm cov kev tiv thaiv tseem ceeb hauvEnterobacteriaceae. Cov kev tshawb fawb tsis ntev los no tau pom tias kev kho oligonucleotide yog ib txoj hauv kev zoo los txo cov kab mob tsis zoo rau kev kho tshuaj tua kab mob [238,239]. Lipid oligonucleotides tau raug pov thawj los ua ib lub tswv yim zoo hauv ob qho tib si xa cov oligonucleotide ib ntus mus rau hauv cov hlwb prokaryotic thiab txo qis qhov tsawg kawg nkaus inhibitory concentration ntawm cov kab mob resistant mus rau tiam thib peb cephalosporin, ceftriaxone [5]. Lub tswv yim ntawm kev tsom mus rau cov tshuaj tua kab mob tiv thaiv cov noob hom phiaj txhawm rau txo qis kev qhia ntawm cov tshuaj tiv thaiv kab mob, uas yuav rov qab muaj kev cuam tshuam rau cov tshuaj tua kab mob pom zoo uas yuav koom nrog cov oligomers. Ntau qhov kev tshawb fawb tau nthuav tawm cov txiaj ntsig ntawm antisense antimicrobials ntawm MDR cov kab mob [230,240,241]. Antisense therapeutics tsom rau NDM-1 noob rov qab muaj kev cuam tshuam rau carbapenems hauv hom kab mob Gram-negative, suav nrogEscherichia coli, Acinetobacter baumannii, thiabPseudomonas aeruginosa[230]. Tib yam tau pom thaum lub hom phiaj ntawm aac(60 )-Ib noob, uas confers tsis kam mus rau aminoglycosides nyob rau hauv ntau Gram-negative soj ntsuam cais tawm [229,237,242,243]. Tam sim no tsis muaj cov tshuaj oligonucleotide pom zoo nyob rau hauv kev ua lag luam rau kev kho mob ntawm cov kab mob; Txawm li cas los xij, muaj qee qhov kev kho mob antisense hauv kev sim tshuaj rau kev kho mob kis kab mob. Fomivirsen, ib qho phosphorothioate oligodeoxynucleotide, yog tib qho kev pom zoo tshuaj tiv thaiv kab mob uas tsom mus rau kis kab mob [229,231,237,244]. Txhawm rau hais txog qhov xav tau sai rau kev txhim kho cov tswv yim tshiab rau kev tshawb pom cov tshuaj tua kab mob tshiab, tseem yuav tsum muaj kev sim ntau ntxiv nrog kev sim tshuaj tiag tiag txhawm rau txhawm rau ua tiav siv lawv hauv kev kho mob ntawm tib neeg cov kab mob sib kis.

8. Faecal Microbiota Hloov

Ib microbiota, lossis "microbial flora", yog ib pawg ntawm cov kab mob (cov kab mob, kab mob, fungi, lossis poov xab) nyob hauv ib puag ncig tshwj xeeb. Tib neeg lub cev yog lub tsev sib txawv microbiota nyob rau ntawm daim tawv nqaij, qhov ncauj kab noj hniav, kab mob ua pa, qhov chaw mos los yog txoj hnyuv. Tib neeg muaj cov kab mob ntau dua li tib neeg lub hlwb [245]. Lub plab hnyuv microbiota txhais tau tias yog cov microbiota ntau tshaj plaws hauv tib neeg lub cev nrog ntau dua 100, 000 billion kab mob (1 txog 2 kg ntawm cov kab mob). Nws yog tam sim no suav hais tias yog ib qho khoom nruab nrog hauv nws tus kheej txoj cai, muab ntau yam kev ua haujlwm physiological tseem ceeb rau tib neeg. Raws li kev cuam tshuam ntawm ntau qhov tshwm sim, qhov sib npaug ntawm cov kab mob "zoo" thiab "phem" ntawm microbiota tuaj yeem tawg; Qhov kev tsis txaus ntseeg no, hu ua dysbiosis, yog qhov ua rau muaj ntau yam kab mob sib txawv. Fecal transplantation (tseem hu ua fecal transplantation lossis fecal bacteriotherapy) yog tom qab ntawd ib txoj kev kho mob tau [245]. Cov tshuaj tua kab mob ua lub luag haujlwm tseem ceeb hauv cov xwm txheej no los ntawm kev hloov pauv ntau haiv neeg ntawm txoj hnyuv microbiota (thiab tshwj xeeb tshaj yog qhov cuam tshuam uas lawv tau tawm dag zog) thiab los ntawm kev ua kom cov hnyuv ntom ntom ntawm cov kab mob resistant. Lub plab hnyuv microbiota yog nyob rau hauv lub plawv ntawm qhov tshwm sim ntawm cov tshuaj tiv thaiv kab mob, yog ob qho tib si lub reservoir ntawm cov tshuaj tua kab mob enterobacteria thiab "cov neeg raug tsim txom" ntawm kev siv tshuaj tua kab mob, uas xaiv cov kab mob no [245]. Cov txheej txheem ntawm cov tshuaj tiv thaiv tam sim no hauv plab microbiota yog hu ua lub plab resistome. Nws suav nrog cov endogenous lossis "neeg nyob" resistome uas muaj cov kab mob ntawm tus tswv tsev nyob hauv microbiota, thiab cov exogenous los yog txawv txav resistome, muaj li ntawm cov noob tsis kam pab los ntawm cov kab mob hauv kev xa mus los ntawm microbiota [246]. Classically, cov neeg nyob hauv cov resistome suav nrog chromosomal resistance genes tsis cuam tshuam nrog cov qauv txawb. Hloov pauv, qhov hloov pauv hloov pauv feem ntau cuam tshuam nrog cov qauv txawb (xws li plasmids lossis transposons), uas tuaj yeem hloov pauv nrog tus tswv tsev cov kab mob nyob hauv [247]. Raws li kev kho dua tshiab ntawm txoj hnyuv microbiota los ntawm tus neeg pub noj qab haus huv [248]. Fecal microbiota transplantation (FMT) tau siv txij li xyoo pua plaub hauv cov tshuaj suav tshuaj rau kev kho mob ntawm cov neeg mob raws plab hnyav thiab kho cov zaub mov lom. Tseeb tiag, cov txheej txheem no tau piav qhia thawj zaug 1700 xyoo dhau los hauv Suav phau ntawv kho mob "Kev Kho Mob Thaum Muaj Xwm Ceev" los ntawm Suav tus kws kho mob Ge Hong [249]. Tom qab ntawd nyob rau hauv lub xyoo pua 16th, Li Shizhen tau piav txog ntau txoj hauv kev npaj cov quav rau kev npaj rau kev hloov fecal xws li fermented fecal tov, tshiab fecal suspensions, as well as qhuav fecal npaj ntawm qhuav quav [249]. Tom qab nyob rau hauv lub xyoo pua 17th, FMT tau siv nyob rau hauv lub npe ntawm "hloov" nyob rau hauv veterinary tshuaj noj nyob rau hauv lub qhov ncauj los yog rectally rau kev kho mob raws plab, kev kho mob ntawm rumen acidosis thiab kev kho mob ntawm bacillary dysentery los yog shigellosis nyob rau hauv cov tsiaj ua liaj ua teb, cov tsiaj nyeg [250]. Xyoo 1958, tus kws phais neeg Asmeskas Ben Eiseman tau lees paub qhov ua tau zoo ntawm cov txheej txheem ntawm FMT los ntawm qhov chaw mos rau kev kho mob pseudomembranous colitis tom qab kev kawm tiav ntawm plaub tus neeg mob kho nrog cov quav quav (enema) los ntawm tus neeg noj qab haus huv [250]. Nyob rau hauv 1983, qhov kev ua tau zoo ntawm kev kho mob rov tshwm simClostridium dificileKev kis mob los ntawm FMT tau tshaj tawm los ntawm Dr. Anna Schwan hauv phau ntawv xov xwm "Lub Lancet" [251].

8.1. Cov ntawv thov hauv Tshuaj

Digestive decontamination muaj nyob rau ntawm qhov ncauj thiab/los yog parenteral tswj cov tshuaj tua kab mob kom tshem tawm cov kab mob pathogenic thiab/los yog ntau cov kab mob resistant thaum sparing commensal kab mob (tshwj xeeb yog cov kab mob anaerobic) kom ntau li ntau tau [252]. Digestive decontamination tam sim no tau siv feem ntau los tshem tawm cov kab mob enterobacteria (tiv taus lossis tsis muaj) hauv cov kab mob neutropenic lossis ntau cov kab mob tiv thaiv kab mob uas muaj feem cuam tshuam rau kev kis mob hauv cov tsev kho mob hnyav [247]. Cov kab mob tiv thaiv kab mob tshwm sim thiab, tshwj xeeb, carbapenemase-uaEnterobacteriaceae, yog cov teeb meem kev noj qab haus huv loj zuj zus tuaj. Lawv txoj kev tswj hwm hauv tsev kho mob, tswj hwm los ntawm tsab ntawv ceeb toom ntawm Fab Kis Lub Tsev Haujlwm Saib Xyuas Kev Noj Qab Haus Huv rau Kev Noj Qab Haus Huv, suav nrog kev ntsuas ntawm kev sib cais ntxiv, pab pawg, thiab tshuaj xyuas cov neeg sib cuag, uas yog qhov nyuaj heev, raug nqi thiab nyuaj rau kev thov [247]. Kev tswj cov tshuaj tua kab mob ntawm cov colonizations no tsis yog tsuas yog tsim kev puas tsuaj tab sis tsis tsim nyog kiag li. Ob qhov chaw kho mob, ib qho hauv Netherlands, qhov thib ob hauv Fabkis, muaj, ntawm qhov tod tes, tau qhia txog kev ua tau zoontawm FMT nyob rau hauv cov ntaub ntawv ntawm colonization los ntawmEscherichia colithiab carbapenemase-uaKlebsiella pneumoniae[253]. Ntau qhov kev tshawb fawb tab tom tshawb nrhiav qhov kev xaiv kho mob no [247,254]. Stripling thiab al. tau tshaj tawm, nyob rau hauv ib tsab ntawv ceeb toom, daim ntawv thov ntawm FMT rau lub plawv-mob hloov cov neeg mob raug kev txom nyem los ntawm vancomycin-resistant enterococcal colonization, concomitant nrog recurrent.Clostridium dificilemob plab [255]. Transplantation ua rau kev kho mob ntawm tus kab mobClostridium difficileKev kis kab mob thiab txo qis ntawm qhov sib piv ntawm vancomycin-resistant enterococci isolates [256]. Txoj kev lis ntshav ntawm fecal npaj los ntawm tus neeg noj qab haus huv pub dawb rau hauv tus neeg mob lub plab zom mov tau raug npaj los ua ib txoj hauv kev kho tshiab los kho cov kab mob cuam tshuam nrog cov kab mob pathological tsis txaus hauv cov neeg nyob hauv microbiota, hu ua dysbiosis [257]. Nws tau siv los kho cov kab mob plab hnyuv xws li IBD thiabClostridium dificilekev kis kab mob, tab sis tseem tsis tau muaj ntaub ntawv qhia txog nws lub luag haujlwm hauv kev kho MRSA enteritis. Ntawm no, peb tau tshaj tawm tsib kis ntawm MSRA enterocolitis kho los ntawm FMT ua ke nrog vancomycin [258]. Thawj zaug, peb tshaj tawm cov kev hloov pauv hauv cov quav microbiota thaum lub sijhawm kho [257]. 

8.2. Kev txwv

Cov kev mob tshwm sim cuam tshuam nrog kev hloov fecal: tshwm sim los ntawm FMT meta-kev tshuaj ntsuam txog cov quav tso tawm los ntawm tus neeg noj qab haus huv rau hauv lub plab ntawm tus neeg mob kom rov qab muaj qhov sib npaug ntawm lawv lub plab flora [259]. Cov txheej txheem no tau raug soj ntsuam feem ntau los kho qhov rov tshwm sim duaClostridium difficilekab mob. Cov ntaub ntawv scientific yog dominated los ntawm cov ntaub ntawv kawm me me nrog cov qauv tsis txaus ntawm cov qauv ntsuas. Kev tshuaj xyuas cov ntaub ntawv suav nrog 109 cov ntawv tshaj tawm piav qhia txog cov txheej txheem no tau ua hauv 1555 tus neeg mob. Rau 1190 ntawm lawv, qhov taw qhia yog qhov rov tshwm sim ntawmClostridium nyuajkab mob [257]. Rau lwm tus, kev hloov fecal feem ntau tau ua los kho cov kab mob plab hnyuv loj (IBD). Cov txheej txheem kuj tau raug tshawb xyuas hauv plab hnyuv siab raum, metabolic syndrome, thiab cem quav. Raws li lub Kaum Hlis 2014, peb qhov kev sim tshuaj ntsuam xyuas tuaj yeem suav tau: ib qho hauv cov kab mob metabolic, ib qho hauv cov kab mob ulcerative thiab ib qho rauClostridium nyuajkab mob. Txoj kev tswj hwm tau teev tseg rau 946 tus neeg mob. Feem ntau (ntau tshaj 500) tau hloov pauv los ntawm colonoscopy. Nws tau ua los ntawm enema rau ntau tshaj 156 tus neeg mob thiab los ntawm lub raj nasogastric rau 133. Qhov kev tshuaj xyuas me me no tsom mus rau 1190 tus neeg mob uas tau txais kev hloov fecal rau recurrent.Clostridium diificile kab mob. Ib kis ntawm fecal perforation tshwm sim thaum lub sij hawm fecal transplantation, yuav tsum tau colectomy [257,260]. Ob kis ntawm norovirus paug tau raug tshaj tawm, nrog rau plaub kis ntawm Gram-negative bacteremia, ob qho uas ua rau tuag. Ntawm cov neeg mob kuj raug kev txom nyem los ntawm IMiC, nyob rau hauv rau qhov mob fecal transplantation tau ua los kho covClostridium difficileTus kab mob tau ua raws li qhov exacerbation ntawm tus kab mob inflammatory. Hauv qhov qhia tau hais tias, kwv yees li kaum tus mob febrile thiab txog ib puas tus mob plab hnyuv me (xws li xeev siab, mob plab, cem quav, thiab lwm yam). Ntxiv rau qhov kev tuag uas tshwm sim tom qab bacteremia, peb lwm tus tau sau tseg. Rau ib qho ntawm cov neeg mob, cov neeg tshawb xyuas tau txiav txim siab tias qhov kev sib txuas ntawm qhov septic shock ua rau kev tuag thiab kev hloov fecal yog "tsis meej". Rau lwm tus neeg mob, nws yog sedation xa mus ua qhov colonoscopy uas ua txhaum. Ib tug thib peb tus neeg mob tuag ntawm septic shock. Raws li kev tshuaj loog dav dav, nws tau regurgitated fecal teeb meem qhia los ntawm endoscopy thiab tom qab ntawd poob raug tsim txom los ntawm kev nqus pa ntsws. Lwm qhov kev tuag uas tau tshwm sim nyob rau lub sijhawm ntev tau tshaj tawm yam tsis muaj qhov txuas mus rau kev hloov pauv tau tsim. Rau 226 tus neeg mob kho rau IMiC, qhov tshwm sim feem ntau yog mob febrile (14 kis). Ob tus kws sau ntawv tau sau tseg rau qhov ua rau mob hnyav ntawm cov kab mob ua rau mob thiab 28 qhov kev mob plab hnyuv: flatulence, ntuav, thiab mob plab [257]. Zuag qhia tag nrho, cov kws sau ntawv xav txog cov ntaub ntawv ntawm kev hloov pauv fecal "tsis zoo" thiab cov lus pom zoo tam sim no "tsis txaus" tso cai rau cov kws kho mob kom paub meej. Raws li lawv cov kev txheeb xyuas ntawm cov ntaub ntawv, lawv xav txog cov txheej txheem "feem ntau muaj kev nyab xeeb", thaum taw qhia cov lus ceeb toom ntawm ntau qhov xwm txheej ntawm cov xwm txheej tsis zoo. Txawm li cas los xij, tsis muaj ib tus neeg sib piv, nws tsis tuaj yeem txiav txim siab ntau npaum li cas ntawm cov kev mob tshwm sim no cuam tshuam txog kev noj qab haus huv thawj zaug [257].

9. Quorum-Sensing Inhibitors

Quorum sensing (QS) yog ib qho kev sib txuas lus hauv xov tooj ntawm tes uas tswj cov kev qhia gene nyob rau hauv kev tswj hwm ntawm cov neeg ntawm tes [261]. Nws tswj cov kev qhia ntawm ntau yam proteins ntawm cov cell ceev. Cov kab mob hlwb tsim cov tshuaj hormones me me zoo li lub npe hu ua acyl-homoserine lactone (AHL) molecules thiab ua lub luag haujlwm hauv lub teeb liab, yog li lawv raug hu ua cov teeb liab molecules [262]. Cov molecules no tau txais los ntawm lwm cov kab mob uas yog ib feem ntawm lawv cov teeb liab, hu ua QS. Cov kab mob kab mob muaj ntau cov proteins sib txawv, ib qho ntawm lawv yog AHL synthase, uas ua rau AHL molecules uas tau tawm sab nraud ntawm tes ntawm cov ntsiab lus tshwj xeeb thiab khi nrog QS receptors [262]. Cov receptors no pib hloov pauv ntawm ntau yam noob. QS tswj ntau yam tseem ceeb hauv cov kab mob: kev ua phem, kev txav, kev loj hlob, biofilm, proteases, thiab elastase, thiab lwm yam ua rau nws ua tus ncej hauv feem ntau cov kab mob [263]. Qhov taw qhia molecule no yog tsim los ntawm ob lub ntsiab lus tseem ceeb: ib lub nplhaib homoserine lactone thiab fatty acid sidechain, tseem hu ua acyl saw [264]. Cov tshuaj tiv thaiv kab mob tuaj yeem siv ib leeg lossis ua ke nrog cov tshuaj tua kab mob thiab lawv lub hom phiaj, tsis zoo li cov tshuaj tua kab mob, tsis yog tua cov kab mob tab sis tiv thaiv lossis tiv thaiv nws lub peev xwm ua kom muaj kab mob [265]. Lawv qhov tshwj xeeb ntawm cov kab mob piav qhia tsawg dua cov tshuaj tiv thaiv tsis zoo ntawm tus tswv microbiota thiab kev xaiv tsis muaj zog rau cov tshuaj tiv thaiv [266]. 

9.2 ib. Kev txwv

Nws tau raug pov thawj tias kev tiv thaiv rau QS kev kho mob tuaj yeem tshwm sim los ntawm kev hloov pauv ntawm cov noob encoding efflux twj. Hauv cov qauv silico tuaj yeem yog qhov kev daws teeb meem rau qhov kev txhim kho no [271]. QS txoj kev kho tau pom tias muaj kev cuam tshuam rau tib neeg kev noj qab haus huv, cov kev mob tshwm sim suav nrog kev hloov pauv ntawm kev ua haujlwm metabolic ntawm microbiota [272], tab sis kuj ua raws li chemoattractant rau neutrophils. Tsis tas li ntawd, nws tau raug pov thawj los ua kom muaj qhov ua rau muaj kev mob tshwm sim thiab cov lus teb pro-apoptotic hauv cov hlwb eukaryotic [273]. Qhov no tuaj yeem ua rau muaj qhov ua rau muaj kev mob tshwm sim tom qab siv QS inhibitors. Ntxiv mus, cov txiaj ntsig kawg ntawm QS txoj kev kho zoo li nyob ntawm ntau qhov ua rau suav nrog kev tiv thaiv kab mob ntawm tus neeg mob, qhov muaj peev xwm ntawm cov kab mob ntawm cov kab mob thiab ib puag ncig.tej yam kev mob tshwm sim thaum kis tus kab mob [274]. Lub hom phiaj ntawm kev kho mob tiv thaiv kab mob yog twb paub thiab tus yam ntxwv. Kev tshuaj xyuas ntawm cov tsev qiv ntawv tshuaj lag luam tso cai rau kev nrawm nrhiav cov molecules nrog cov khoom siv tshuaj zoo uas yuav pab daws cov teeb meem loj hlob ntawm cov kab mob multidrug-resistant.

Ib lub sijhawm tshiab yog pib hnub no nrog rau kev tshawb fawb ntev-awaited loj hlob ntawmtshiab anti-kev kis kab mobtiv thaiv MDR cov kab mob. Cov txheej txheem kho mob no yog qhov tseebmuaj zog uas tsis yog tshuaj tua kab mob kev xaiv los txo qhov nce loj hauvtshuaj tua kab mob tiv thaiv kab mobuaspeb tab tom ntsib niaj hnub no. Nws tsis tuaj yeem tsis lees paub tias cov txheej txheem ntawm kev ua ntawm cov kev kho mob nonyuaj los piav qhia txog thiab qhov ntawdkev sim tshuajtsis tiav txaus los muabcov ntaub ntawv tseem ceeb thiab cov ntsiab lus. Txawm li cas los xij, txhua qhov kev siv zog ua hauv kev ua cov kev kho mob no ua ib qhokev kho mob niaj hnub yuav tsum tau ua nrog ceev fajxav txog qhov efficiencythiab kev nyab xeeb ntawmtxhua txoj kev kho. Thaum kawg, peb ntseeg tau tias kev paub thiab kev txawj ntse ntawm kev tawm tsamcov qauv thiab cov txheej txheem ntawm kev txiav txim yuav tso cai rau cov kws kho mobnce tsav antimicrobialkev kho mobmus rau tus kheej thiabkev kho mob mus kom ze. 

Tus sau kev koom tes:Conceptualization, MK-H.; txhua tus kws sau ntawv tau koom nrog kev sau ntawv - keeb kwmkev npaj npaj; sau—kev tshuaj xyuas thiab kho, HAM, RB (Rachid Benmessaoud), HY, LS, HGA, MH, RB (Rihabe Boussettine), NF-A., FAL, ID, MME thiab MK-H.; kev saib xyuas,MK-H. thiab MME Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.

Nyiaj txiag:Qhov kev tshawb fawb no tsis tau txais nyiaj txiag sab nraud. Tsab xov xwm Kev Them Nqi (APC) yog them los ntawmMohammed VI University of Health Sciences (UM6SS).

Kev tsis sib haum xeeb ntawm kev txaus siab:Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab. Cov nyiaj txiag tsis muaj lub luag haujlwm hauv kev tsimntawm kev kawm; hauv kev sau, txheeb xyuas, lossis txhais cov ntaub ntawv; nyob rau hauv kev sau ntawv, los yoghauv kev txiav txim siab tshaj tawm cov txiaj ntsig.

Cov ntaub ntawv

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