C ch c lc ca vi khun

Bch khoa ton th m Wikipedia Cc bnh l nhim trng l nguyn nhn gy t vong hng u trn th gii. Khng ch c nhng bnh nhim trng mi pht sinh m nhng bnh nhim trng c gy cht ngi bit t lu cng ti xut hin. Hn na t l vi khun gy bnh khng khng sinh ngy cng tng cao l nguy c ln cho sc khe cng ng. Nhng bng chng gn y cho thy cc tc nhn gy bnh mc d rt khc nhau u s dng nhng phng thc chung pht ng qu trnh nhim trng v gy bnh. Nhng c ch ny to nn c lc (virulence) ca vi khun. Tm hiu cc c ch m vi khun s dng xm nhp v gy bnh c ngha quan trng trong cuc chin chng li cc tc nhn b nh ny. Vy cc tc nhn gy bnh t hon ny , ang v s s dng nhng loi v kh no to nn c lc ca chng? Sau y l nhng bn lun v cc chin lc gy bnh chung ca cc vi khun m y hc hiu phn no.

Mc lc
[n]

1 Cc yu t bm dnh 2 Kh nng xm nhp 3 V vi khun 4 Vch t bo vi khun 5 Cc c t 6 Kh nng k sinh ni bo 7 khng khng sinh 8 Trin vng nghin cu v iu tr 9 Ti liu tham kho

[sa] Cc yu t bm dnh
Bc quan trng u tin trong qu trnh tng tc gia tc nhn gy bnh v vt ch l s bm dnh (adherence) ca chng vo cc b mt ca vt ch. Cc b mt ny bao gm da, nim mc (khoang ming, mi hu, ng tit niu) v cc t chc su hn (t chc lympho, biu m d dy rut, b mt ph nang, t chc ni m). C th to ra nhiu lc c hc khc nhau nhm loi b cc vi sinh vt khi cc b mt ny nh bi tit nc bt, ho, ht hi, dch tit nim mc, nc tiu, nhu ng rut v dng mu chy. Mt c im chung ca cc tc nhn gy bnh l kh nng biu hin cc yu t gip chng bm vo cc phn t trn nhiu loi t bo khc nhau ca vt ch v gip chng chng chu c cc lc c hc ny. Mt khi bm dnh vo b mt t bo vt ch, tc nhn gy bnh c kh nng khi ng cc qu trnh ha sinh c hiu gy bnh nh tng sinh, bi tit c t, xm nhp v hot ha cc chui tn hiu ca t bo vt ch. Cc yu t bm dnh ca vi sinh vt c gi l cc adhesin. Chng c th c bn cht polypeptide hoc polysaccharide.

Cc adhesin c bn cht polypeptide c chia thnh hai nhm: nhm c fimbriae v nhm khng c fimbriae. Cc fimbriae, hay cn gi l cc pili, l nhng cu trc ph ca vi sinh vt c dng nh si lng trn b mt vi khun. Cc fimbriae c cu to bi nhiu protein xp cht vi nhau to nn hnh dng ging nh tr xon c. Thng th ch c mt loi protein l cu trc chnh ca mt phn nhm fimbriae tuy nhin cc protein ph tr khc cng c th tham gia vo cu trc ca nh hoc gc fimbriae. nh ca cc fimbriae c chc nng gn vi t bo vt ch. Cc vi khun Gram m thng bm dnh nh cc fimbriae ny nh E coli (gy vim d dy rut v nhim khun tit niu), V cholera, P aeruginosa v cc loi Neisseria. Thut ng yu t bm dnh khng phi fimbriae (afimbrial adherin) dng ch cc protein c chc nng bm dnh nhng khng to thnh cu trc di, a phn nh fimbriae. Cc yu t bm dnh khng phi fimbriae thng iu khin qu trnh tip xc mt thit vi t bo vt ch tuy nhin qu trnh ny ch xy ra mt nhm nh cc loi t bo nht nh nu so vi kh nng gn c vi rt nhiu loi t bo khc nhau ca fimbriae. Cc vi khun Gram m (Yersinia pseudotuberculosis, E coli gy bnh l rut, cc Neisseria), cc vi khun Gram dng (Staphylococcus, Streptococcus) v cc Mycobacteria l nhng tc nhn gy bnh c yu t bm dnh khng phi fimbriae. Cc yu t bm dnh bn cht polysaccharide thng l thnh phn cu to ca mng t bo, vch t bo v v vi khun. Teichoic acid trong vch ca vi khun c tc dng nh l cc yu t bm dnh ca Staphylococcus v ca Streptococcus. Cc polysaccharide (glucan v mannan) trong lp v ca Mycobacteria cng c cc th th ca vt ch nhn din (receptor b th 3 v mannose receptor) nh lm tng tnh bm dnh ca cc tc nhn ny. Mc d cc tng tc receptor-ligand nhm tng cng kh nng bm dnh c th chia thnh hai nhm chnh: tng tc protein-protein v protein-carbonhydrate, mt iu quan trng cn nh l cc vi sinh vt thng s dng rt nhiu th th khc nhau ca t bo vt ch. E coli gy bnh l rut (Entero-pathogenic E coli: EPEC) bm trc tip protein c chc nng th th ca chnh n vo trong t bo vt ch. Mt khi trong mng t bo vt ch, cc th th ny s gn vi cc yu t bm dnh khng phi fimbriae trn b mt t bo vi khun to thun li cho qu trnh bm dnh. Mt iu quan trng cn nh l mt tc nhn gy bnh thng biu hin nhiu yu t bm dnh khc nhau. Chin lc ny c hu ht cc loi vi khun (Gram m, Gram dng v mycobacteria) s dng. Mt hng tp trung nghin cu iu tr hin ti l pht trin cc vaccine hoc thuc phong b kh nng bm dnh.

[sa] Kh nng xm nhp

Mt khi gn vo b mt t bo vi khun, mt s tc nhn gy bnh tip tc tin su vo hn na trong c th vt ch tip tc chu trnh nhim trng. Qu trnh ny gi l s xm nhp (invasion). C th chia qu trnh xm nhp thnh hai loi: ni bo v ngoi bo. Xm nhp ngoi bo xy ra khi tc nhn gy bnh ph v cc ro cn ca t chc pht tn n cc v tr khc trong c th nhng bn thn chng vn tn ti bn ngoi t

bo vt ch. Phng thc xm nhp ngoi bo c s dng bi lin cu khun tan mu nhm A (Group A -haemolytic streptococcus) v t cu vng (Staphylococcus aureus). Cc chng vi khun ny tit mt s enzyme ph hy cc phn t ca t bo vt ch:

Hyaluronidase: ct t cc proteoglycan t chc lin kt. Streptokinase v staphylokinase: ph hy cc cc fibrin. Lipase: ging ha cc loi m ca vt ch c tch t li Nuclease: tiu hy cc ARN v ADN c gii phng ra. Cc haemolysin to cc l thng trn mng t bo c kh nng ly gii khng ch cc hng cu m c cc loi t bo khc na. Haemolysin cng tham gia vo s pht tn vi khun rng hn trong t chc vt ch. Elastase ca trc khun m xanh c kh nng ging ha cc phn t ngoi bo v gip vi khun xm nhp t chc vi cc biu hin lm sng nh vim mng keratin, hoi t t chc trong bng v to cc x nang.

Kh nng xm nhp ngoi bo cho php cc tc nhn gy bnh ny to ra cc ch n np trong t chc v ti chng c th tng sinh ri pht tn vo cc v tr khc ca c th cng nh sn xut cc c t v khi ng cc p ng vim. Cc tc nhn gy bnh xm nhp ngoi bo cng c th i vo bn trong t bo v s dng c hai con ng xm nhp ni bo v ngoi bo. Xm nhp ni bo xy ra khi cc vi sinh vt thc s i vo bn trong t bo ca vt ch v sng trong mi trng ni bo ny. Mt s cc tc nhn gy bnh l vi khun Gram m, vi khun Gram dng v cc Mycobacteria c kh nng sng bn trong t bo. Cc t bo thc bo ln t bo khng c chc nng thc bo u l ch tn cng ca cc tc nhn ny. Mt s tc nhn gy bnh c i sng k sinh ni bo bt buc ngha l chng buc phi sng bn trong t bo cc ng vt c v mi c th pht trin c. Cc tc nhn ny bao gm Chlamydia, Rickettsia v Mycobacterium leprae. Cc chng vi khun khc thuc loi k sinh ni bo khng bt buc ch s dng kh nng xm nhp ni bo nh l phng tin tng sinh v pht tn n cc t chc khc.

[sa] V vi khun
Mt s vi khun sn xut mt lng ln cc phn t polysaccharide trng lng phn t cao, cn c gi l exopolysaccharide. Lp o ngoi bo ny c gi l v vi khun (capsule). Kh nng sn xut v l mt trong nhng yu t c lc quan trng nht ca vi khun v phng din xm nhp ti v tr vim. Mt cch c th hn, v vi khun gip chng chng li c ch phng v ca c th cng nh khng khng sinh. V mt s vi khun cng c kh nng iu ha min dch. V ny bo v vi khun chng li s thc bo bng cch khng cho cc khng th to hin tng opsonin ha trn vch vi khun. Do khng c hin tng opsonin ha nn cc i thc bo v bch cu trung tnh tip cn km hoc khng th tip cn c vi khun. Hin tng "thc bo bt lc" ny cng lm cho phn ng vim thm mnh m bi cc t bo thc bo khng th tiu dit c vi khun cng c gng tit nhiu cytokine hn na trong n lc lm sch vi khun ni y. Phn ng ny li thu ht thm nhiu cc bch cu a nhn v i thc bo khc na n vim. Cc loi vi khun nguy him c kh nng to v l Streptococcus pneumoniae (ph cu khun),

Neisseria meningitidis (no m cu khun) v Pseudomonas aeruginosa (trc khun m xanh).

[sa] Vch t bo vi khun

Vi khun c chia thnh hai nhm chnh da trn s khc bit cu trc vch t bo (cell wall): vi khun Gram dng v vi khun Gram m. Vch t bo ca c hai nhm u cha cc thnh phn gy c c xem l nhng yu t c lc mnh ng vai tr trung tm trong qu trnh bnh sinh ca ca sc nhim trng huyt. Cc thnh phn c t ca vch t bo khng nhn l nhng thnh phn cu trc c bn rt t gii phng vo mi trng xung quanh nu t bo khng b cht v b ly gii. Mt iu tri khoy l cc khng sinh s dng trong lm sng li lm gi phng mt lng ln cc thnh phn gy c ny. Do li lm xu hn tnh trng bnh sn c cng nh tin lng ca bnh nhn. Nhiu bng chng khoa hc cho thy rng vi khun Gr (-) v vi khun Gr (+) cng dng chung mt chin lc gy nhim khun huyt. Nhim trng huyt l hu qu t cc tc ng lin hp ca cytokine, cc thnh phn b th v cc thnh phn ca con ng ng mu. Cc thnh phn ca vch vi khun c th gy nn s sn xut hoc hot ha cc cht trung gian iu ha ny. Tht vy, cc bin c trc tip gy nn nhim trng huyt l qu trnh gii phng cc ni c t (endotoxin hay lipopolysaccharide) hoc gii phng cc thnh phn gy c khc ca vch vi khun vo trong h tun hon. Lipopolysaccharide (LPS) vi khun l mt phn t lng tnh nm trong lp mng ngoi ca vch vi khun Gram m thng c xem l yu t chnh chu trch nhim trong qu trnh gy nn sc nhim trng huyt. Th th chnh ca LPS l CD14, mt marker b mt ca i thc bo. Lipid A, thnh phn gy c ca phn t LPS, gy nn s gii phng hng lot cc cytokine gy vim v hot ha h thng b th v con ng ng mu. Cc nghin cu gn y cho thy cc th th ging Toll (Toll-like receptor), cytokine vim, eicosanoid, gc t do xy ha, yu t c ch di chuyn i thc bo, cc protein kinase truyn tn hiu v cc yu t sao m u ng vai tr quan trng trong sinh bnh hc ca sc nhim trng huyt do vi khun Gram m. Cc mnh Peptidoglycan v teichoic acid trong vch t bo vi khun Gram dng c kh nng to nn nhiu hiu ng sinh l bnh ging nh LPS. Peptidoglycan v teichoic acid ca vi khun Gram dng l thnh phn khi ng chnh ca nhim trng huyt do nhm vi khun ny. Cc thnh phn ca vch t bo c vi khun Gram m v vi khun Gram dng u tc ng ch yu thng qua khi ng p ng vim bng cch hot ha cc monocyte, i thc bo. Cc t bo ny khi c hot ha s gii phng mt lot cc cytokine, c bit l TNF v interleukin-1. Mc khc, c ni c t ln peptodoglycan u c th hot ha h thng b th. S hot ha ny li lm gii phng TNF t cc monocyte v gy nn tp trung cc bch cu trung tnh v lm co mch phi. Nh vy, bt k nhim trng huyt gy nn do vi khun Gram dng hay vi khun Gram m, du hiu v triu chng nhim trng u kh tng t nhau.

[sa] Cc c t
c t (toxin) l cc v kh sinh hc c bn cht protein hoc khng phi protein c sn xut bi vi khun nhm tiu dit cc t bo vt ch. Cc v d v c t khng phi protein l ni c t (LPS) ca cc vi khun Gram m v teichoic acid ca cc vi khun Gram dng. Cc c t bn cht protein (ngoi c t) thng l cc enzyme i vo t bo c nhn bng hai phng thc: (1) tit vo mi trng ln cn hoc (2) trc tip bm vo bo tng ca t bo vt ch thng qua h thng tit loi III (type III secretion system) hoc mt s c ch khc. Cc ngoi c t vi khun c th tm chia thnh 4 loi chnh da trn thnh phn cu trc amino acid cng nh chc nng ca chng:

c t A-B, c t tiu protein, c t hnh thnh l thng, v Cc c t khc.

Mt s chng vi khun c c t A-B l P. aeruginosa, E. coli, Vibrio cholerae, Corynebacterium diphtheria v Bordetella pertussis. Cc c t A-B c hai phn: tiu n v A c hot tnh enzyme v tiu n v B chu trch nhim gn v a c t vo t bo vt ch. Hot tnh enzyme ca tiu n v A c th c hot tnh tiu protein v d nh c t tetanus v botulinum hoc c hot tnh ADP ribosyl ha (ADP ribosylating activity) nh c t ca vi khun t, ho g, bch hu v c t A ca trc khun m xanh. Cc c t tiu protein ph hy cc protein vt ch c hiu gy nn nhng c tnh lm sng ring ca bnh. V d c t botulinum ca Clostridium botulinum, c t tetanus ca Clostridium tetani, elastase v protease IV ca P. aeruginosa. c t botulinum c a vo bng ng tiu ha v gy nn lit mm (flaccid paralysis) cc dy thn kinh ngoi bin trong khi c t tetanus hnh thnh cc vt thng su v gy nn lit cng (spastic paralysis) do nh hng n thn kinh trung ng. Elastase v protease IV ca trc khun m xanh ph hy cc cht c bn ca t bo, cho php nhim trng lan ta n cc khu vc rng hn. Cc c t ph v mng t bo hin din mt s vi khun. c t ny c kh nng to l thng trn mng t bo vt ch gy ly gii t bo. Cng ngy cng c nhiu c t to l thng mng t bo c pht hin cc vi khun Gram m nh h RTX (Repeat arginine Threonine X motif). Mc d c ch to l thng ging nhau cc thnh vin ca h ny, cc t bo ch li khc nhau. Cc c t khc bao gm: cc protein dng enzyme thy phn globulin min dch A (immunoglobulin A protease-type protein), cc c t bn vi nhit hot ha Guanylate cyclase v cc c t lm thay i khung nng (cytoskeleton) ca t bo vt ch. Nh vy, vi khun c kh nng s dng nhiu phng thc khc nhau nhm ph hy cc con ng truyn tin cng nh tnh ton vn cu trc ca t bo thit lp v duy tr nhim trng. Hin nay y hc bt u hiu c c ch phn t ca cc tc ng do c t. iu ng mng l mt s cc c t quan trng trn y c chung

nhng motif cu trc v sinh ha. Chng ta c th li dng c im ny pht trin cc phng php tr liu trong tng lai v cc phng php ny c th hiu qu chng li nhiu vi khun khc nhau.

[sa] Kh nng k sinh ni bo

Vi khun gy bnh tin ha v pht trin nhng c ch sng st v nhn ln bn trong t bo vt ch sau khi xm nhp. Cc t bo vt ch c th cha ng vi khun ni bo gm cc t bo khng c chc nng thc bo (nh cc t bo biu m v t bo ni m) v c thc bo chuyn nghip nh i thc bo v bch cu trung tnh. Kh nng sng st v nhn ln c bn trong cc thc bo chuyn nghip l iu ng ngc nhin bi cc t bo c trang b cc v kh c sc cng ph mnh m tiu dit vi khun b nut vo. Cc c ch tiu dit mm bnh ny bao gm s sn xut cc cht trung gian c kh nng xy ha, pH thp bn trong cc khng bo cha vi khun v s hot ha cc enzyme tiu hy protein. Thng c ba ni n tr m vi khun s dng n np bn trong t bo. Cc v tr ny bao gm:

Bn trong cc khng bo tiu th-thc bo th (lysophagosome) c kh nng thy phn v c tnh acid, Bn trong cc khng bo cha ha mng vi tiu th, v Bn trong dch bo tng.

Coxiella burnetti l mt v d v kh nng vi khun sng bn trong cc mi trng c ca khng bo tiu th-thc bo th. Chnh pH thp l iu kin cn thit tc nhn ny tng sinh. Cc chng Mycobacterium, Salmonella, Legionella pneumophila v Chlamydia trachomatis thuc nhm c tr bn trong cc khng bo cha ha mng vi tiu th. Cc khng bo b cc vi khun ny chim c c xem l c "c bit ha" hoc c "ti cu trc" v v mt hnh th chng thng khc bit vi cc khng bo khc trong t bo v cha cc marker b mt c trng. Shigella flexneri, L monocytogenes v Rickettsia rickettsii l nhng tc nhn gy bnh sng trong dch bo tng. Cc vi khun ny c cng chung mt chin lc dng enzyme ph hy cc khng bo ln cn v pht tn ni bo thng qua s dng cc khung nng ca t bo. Cc vi khun k sinh ni bo c th nhn ln v lan trn n cc t bo khc trong vng nhim trng hoc c th i xa hn. Chlamydia v Rickettsia ly gii mng t bo vt ch, phng thch cc t vi khun gy nhim trng, cc vi khun ny s bm v xm nhp cc t bo ln cn. Ngoi tc ng lm ly gii t bo vt ch, Shigella v Listeria cn s dng mt con ng lan truyn t t bo n t bo thng qua vic truyn trc tip mt phn cu trc t bo nhim bnh cho t bo lnh ln cn. Cc t bo nhim vi khun ny to ra cc phn li vo t bo lnh, sau phn li ny s ha mng vi t bo lnh v to nn cc khng bo cha vi khun bn trong t bo lnh. Cc vi khun k sinh trong i thc bo v bch cu trung tnh cng c kh nng s dng cc thc bo ny nh l cc phng tin chuyn ch gy nhim trng ton thn thng qua h thng mu v bch huyt. Salmonella typhi, cc chng Yersinia v Brucella c xem l c kh nng di chuyn gia cc t chc theo phng thc ny.

Cc vi khun ni bo gy nn nhng vn nghim trng trong mt s bnh l nhim trng. Mt s tc nhn nhim trng ni bo c th tn ti hng nm tri v cn phi s dng mt liu php khng sinh rt mnh m. Nhim trc khun lao Mycobacterium tuberculosis l v d in hnh nht. Trng tm ca cc nghin cu hin ti l nhn din v xc nh c trng ca cc yu t c lc m vi khun k sinh ni bo s dng chim lnh ni n nu kh tip cn ny.

[sa] khng khng sinh

Vic pht minh ra khng sinh lm thay i mang tnh cch mng trong iu tr cc bnh l nhim trng. Tuy nhin vic s dng khng sinh trn lan trong nhng thp k va qua dn n s xut hin rt nhiu chng vi khun khng khng sinh v to nn mt mi nguy c ton cu trm trng e da nn y hc hin i. C vi khun Gram dng v Gram m u c kh nng khng li cc thuc iu tr vi sinh vt. Cc chng vi khun khng khng sinh (mt s ln trong c kh nng a khng) xut hin gy y v l nguyn nhn ca nhng mi lo ngi gm: cc tc nhn gy bnh tiu chy nh Shigella, Salmonella, E coli v Enterococcus faecium; cc tc nhn gy bnh ng h hp nh Klebsiella pneumoniae v P aeruginosa; gy bnh ng tit niu nh E coli, M tuberculosis. Cc tc nhn gy bnh ny vn l nguyn nhn gy t vong do nhim trng hng u trn th gii. Hn na, Staph aureus khng vi methicillin, mt trong nhng nguyn nhn gy nhim trng bnh vin thng gp nht, v cc vi khun Gram m khng vancomycin nh Enterococcus (v c Staph aureus) l nhng thch thc thc s i vi cc bc s lm sng. C ba c ch thng gp ca hin tng khng khng sinh vi khun:

Thay i v tr ch tc ng, Thay i s thu nhn khng sinh, v Bt hot khng sinh.

S pht trin kh nng khng c thc hin thng qua hai qu trnh di truyn: do t bin t pht v ch yu l do thu nhn cc gene t ngun gc bn ngoi thng qua hin tng chuyn gene theo chiu ngang. Hin tng chuyn gene theo chiu ngang xut hin khi cc yu t di truyn c chuyn t mt c th ny n c th khc cng loi hoc khc loi. Ngoi ra, thay i vt cht di truyn a n hin tng khng cng c gy nn bi t bin t pht. V d mt t bin lm thay i v tr gn khng sinh c th lm gim nhy cm khng sinh v lm gia tng khng thuc. c bit, M tuberculosis, tc nhn gy bnh lao, vn l mi e da cho sc khe loi ngi v vi khun ny c kh nng a khng, bao gm khng vi isoniazid v streptomycin. khng vi streptomycin l do vi khun c cc t bin lm thay i cc ch ca khng sinh ny. Kh nng lan trn ca cc vi khun khng khng sinh l mi e da thc s i vi sc khe cng ng trn ton th gii. Qu trnh ny c th thun li nh kh nng to cc biofilm. Cc biofilm ny l cc tp hp vi sinh vt c t chc nh chng c

th chia s kh nng sng st v tng cng khng i vi cc kch tc ca mi trng. S ly lan ny c th xy ra gia ng vt vi ng vt do thc n b nhim cht thi hoc t ng vt ly cho ngi do n phi cc thc n nhim bn, do xut nhp khu ng vt sng hoc cc sn phm ca chng v ly t ngi sang ngi, c bit l trong cc c s chm sc y t. Nguy c to thnh dch (epidemic) hoc i dch (pandemic) l nguy c c tht v n t ra mt thch thc ln cho vic iu tr cc bnh nhim trng trn bnh din ton cu. Do vy cn phi c cc nghin cu pht trin cc thuc mi hiu qu trong vic kim sot v nga s lan trn ny.

[sa] Trin vng nghin cu v iu tr

i mt vi nhng c ch m vi khun s dng gy bnh, cc nghin cu trong tng lai s tp trung vo nhng hng no? Nhng tin b gn y trong k thut khuych i chui ADN (polymerase chain reaction: PCR) v cc k thut ADN khc cho php cc nh khoa hc xc nh nhanh chng b gene hon chnh ca c cc vi sinh vt gy bnh v t bo ca vt ch c nhn cng nh lng gi c mc biu hin gene v m t c cc qu trnh phn t xy ra trong nhim trng. p dng cc phng php ny trong vic nghin cu b gene ca vi sinh vt v t bo vt ch, kt hp vi cc cng c phn tch hiu qu v thang nh gi mc biu hin gene v ang to ra mt cuc cch mng trong vic pht trin cc k thut mi trong chn on, tin lng v x tr lm sng cc bnh nhim trng.

[sa] Ti liu tham kho

J W Wilson, M J Schurr, C L LeBlanc, R Ramamurthy, K L Buchanan and C A Nickerson. Mechanisms of bacterial pathogenicity. Postgraduate Medical Journal. 2002; 78: 216-224 University of Wisconsin-Madison Department of Bacteriology. The Mechanisms of Bacterial Pathogenicity. Todar's Online Textbook of Bacteriology . 2002 Kenneth Todar. http://textbookofbacteriology.net/pathogenesis.html Stephen T. Abedon. Bacterial Mechanisms of Pathogenicity. http://www.mansfield.ohio-state.edu/~sabedon/biol2060.htm