Professional Documents
Culture Documents
net/publication/221818611
Article in The Chinese journal of dental research: the official journal of the Scientific Section of the Chinese Stomatological Association (CSA) · January 2011
Source: PubMed
CITATIONS READS
59 5,477
3 authors:
SEE PROFILE
Some of the authors of this publication are also working on these related projects:
All content following this page was uploaded by C.J. "Jaya" Seneviratne on 11 July 2014.
'HQWDOSODTXHLVDQDUFKHW\SLFDOELRILOPFRPSRVHGRIDFRPSOH[PLFURELDOFRPPXQLW\,WLVWKH
DHWLRORJLFDODJHQWIRUPDMRUGHQWDOGLVHDVHVVXFKDVGHQWDOFDULHVDQGSHULRGRQWDOGLVHDVH7KH
FOLQLFDOSLFWXUHRIWKHVHGHQWDOGLVHDVHVLVDQHWUHVXOWRIWKHFURVVWDONEHWZHHQWKHSDWKRJHQLF
GHQWDOSODTXHELRILOPDQGWKHKRVWWLVVXHUHVSRQVH,QWKHKHDOWK\VWDWHERWKSODTXHELRILOPDQG
DGMDFHQWWLVVXHVPDLQWDLQDGHOLFDWHEDODQFHHVWDEOLVKLQJDKDUPRQLRXVUHODWLRQVKLSEHWZHHQ
WKH WZR +RZHYHU FKDQJHV RFFXU GXULQJ WKH GLVHDVH SURFHVV WKDW WUDQVIRUP WKLV µKHDOWK\¶
GHQWDOSODTXHLQWRDµSDWKRJHQLF¶ELRILOP5HFHQWDGYDQFHVLQPROHFXODUPLFURELRORJ\KDYH
LPSURYHGWKHXQGHUVWDQGLQJRIGHQWDOSODTXHELRILOPDQGSURGXFHGQXPHURXVFOLQLFDOEHQHILWV
7KHUHIRUHLWLVLPSHUDWLYHWKDWFOLQLFLDQVNHHSDEUHDVWZLWKWKHVHQHZGHYHORSPHQWVLQWKHILHOG
RIGHQWLVWU\%HWWHUXQGHUVWDQGLQJRIWKHPROHFXODUPHFKDQLVPVEHKLQGGHQWDOGLVHDVHVZLOO
IDFLOLWDWHWKHGHYHORSPHQWRIQRYHOWKHUDSHXWLFVWUDWHJLHVWRHVWDEOLVKDµKHDOWK\GHQWDOSODTXH
ELRILOP¶E\PRGXODWLQJERWKKRVWDQGPLFURELDOIDFWRUV,QWKLVUHYLHZWKHSUHVHQWDXWKRUVDLP
WRVXPPDULVHWKHFXUUHQWNQRZOHGJHRQGHQWDOSODTXHDVDPLFURELDOELRILOPDQGLWVSURSHUWLHV
LQRUDOKHDOWKDQGGLVHDVH
.H\ZRUGVGHQWDOSODTXHELRILOPKHDOWKDQGGLVHDVHSURSHUWLHV
'HQWDOSODTXHELRILOP±KLVWRULFDODVSHFWV UHVLGLQJLQWKHGHQWDOSODTXH+HQFHGHQWDOSODTXHKDV
EHHQNQRZQWREHDUHVHUYRLURIPLFURRUJDQLVPVVLQFH
7KHUHODWLRQVKLSEHWZHHQPLFURRUJDQLVPVDQGGHQWLVWU\ WKH GDZQ RI PLFURELRORJ\ +RZHYHU XQWLO WKH V
GDWHV EDFN WR WKH HDUOLHVW REVHUYDWLRQV RI PLFURRUJDQ LW ZDV DVVXPHG WKDW PLFUREHV SUHGRPLQDQWO\ OLYH LQ D
LVPV,QDOHWWHUWRWKH5R\DO6RFLHW\LQ6HSWHPEHU VXVSHQGHGSKDVH7KHUHIRUHPRVWVWXGLHVRQPLFURELDO
$QWRQLYDQ/HHXZHQKRHNGHVFULEHGKLVREVHUYDWLRQRI GLVHDVHVDQGGUXJUHVLVWDQFHPHFKDQLVPVZHUHEDVHGRQ
µZKLWHOLWWOHPDWWHUEHWZHHQKLVWHHWK¶DVµDQXQEHOLHY WKLVIUHHIORDWLQJRUµSODQNWRQLF¶PRGHRIJURZWK7KLV
DEOHJUHDWFRPSDQ\RIOLYLQJDQLPDOFXOHVDVZLPPLQJ FRQFHSW ZRXOG KDYH LQIOXHQFHG WKH JHQHVLV RI .RFK¶V
PRUHQLPEO\WKDQDQ\,KDGHYHUVHHQXSWRWKLVWLPHWKH SRVWXODWHV ZKLFK DVVXPHG WKDW D VSHFLILF SDWKRJHQLF
ELJJHVWVRUWEHQW«WKHLUERG\LQWRFXUYHVLQJRLQJIRU DJHQW LV DFFRXQWDEOH IRU D VSHFLILF LQIHFWLRXV GLVHDVH
ZDUGV¶/DWHUVWXGLHVUHYHDOHGWKDWWKHµELJJHVWVRUW¶ ,QLWVHDUO\GD\VGHQWLVWU\HPEUDFHG.RFK¶VSRVWXODWHV
KHUHIHUUHGLQKLVOHWWHUFRXOGEH6HOHQRPRQDVVSHFLHV DQG DWWHPSWHG WR OLQN VSHFLILF SDWKRJHQLF DJHQWV ZLWK
SDUWLFXODUGHQWDOGLVHDVHVVXFKDV6WUHSWRFRFFXVPXWDQV
±ZKLFKZDVGLVFRYHUHGE\&ODUNHDVHDUO\DV±
'HSDUWPHQWRI2UDO%LRVFLHQFHV)DFXOW\RI'HQWLVWU\7KH8QLYHUVLW\
ZLWKGHQWDOFDULHV
RI+RQJ.RQJ+RQJ.RQJ35&KLQD
'HSDUWPHQWRI&RPSUHKHQVLYH'HQWDO&DUH)DFXOW\RI'HQWLVWU\7KH ,W LV RQO\ DV ODWH DV WKH V WKDW SLRQHHULQJVWXG
8QLYHUVLW\RI+RQJ.RQJ+RQJ.RQJ35&KLQD LHV E\ &RVWHUWRQ DQG FROOHDJXHV OHG WR DQ XQGHUVWDQG
LQJ RI WKH FRPPXQLW\ OLIHVW\OH RI PLFURRUJDQLVPV LQ
QDWXUH,QFLGHQWDOO\GHQWDOSODTXHZDVRQHRIWKHILUVW
&RUUHVSRQGLQJ DXWKRU 'U /3 6$0$5$1$<$.( 'HSDUWPHQW RI
2UDO%LR6FLHQFHV)DFXOW\RI'HQWLVWU\7KH8QLYHUVLW\RI+RQJ.RQJ
IHZVDPSOHVXVHGLQWKHVHJURXQGEUHDNLQJVWXGLHVRQ
+RQJ .RQJ 35 &KLQD 7HO )D[ PLFURELDO ELRILOPV &RVWHUWRQ DQG FROOHDJXHV VKRZHG
(PDLOODNVKPDQ#KNXKN WKDWPLFURELDOFHOOVDGKHUHWRWKHWRRWKVXUIDFHDQGIRUP
Fig 1 Sequence of biofilm development. A
biofilm typically develops in four sequential
steps: first, adhesion of a microorganism to
a surface; second, individual colonisation
and organisation of cells; third, secretion of
EPSs and maturation into a three-dimen-
sional structure; and finally, dissemination of
progeny biofilm cells. (Reprinted with the per-
mission of Oral Diseases, Blackwell Munks-
gaard).
D PLFURELDO FRPPXQLW\ DV RSSRVHG WR WKH FRPPRQ ELRILOP DV FRQYHQWLRQDO FXOWXUHEDVHG WHFKQLTXHV KDG
QRWLRQDWWKDWWLPHWKDWPLFUREHVOLYHDVIUHHO\IORDWLQJ RQO\OLPLWHGVXFFHVVLQUHFRYHULQJSODTXHPLFURELRWD
RUJDQLVPV LQ VXVSHQVLRQV ,W LV QRZ ZLGHO\ DFFHSWHG 8VH RI WKH PHWDJHQRPLFV DSSURDFK KDV LQGLFDWHG WKDW
WKDW PRVW LI QRW DOO PLFURRUJDQLVPV LQ QDWXUH SUHIHU WKH QXPEHU RI EDFWHULDO VSHFLHV LQ WKH PDWXUH GHQWDO
DEO\ OLYH DV VXUIDFH DGKHUHQW PLFURELDO FRPPXQLWLHV SODTXHELRILOPFRXOGEHDVKLJKDV,WLVDOVR
RU µELRILOPV¶ 0RUH LPSRUWDQWO\ LW KDV EHHQ UHYHDOHG QRWHZRUWK\ WKDW WKH FRPSRVLWLRQ RI WKH GHQWDO SODTXH
WKDW DW OHDVW RI DOO LQIHFWLRXV GLVHDVHV DUH OLQNHG ELRILOPLVKLJKO\GLYHUVHEHWZHHQLQGLYLGXDOVDQGWKHVH
WRWKHELRILOPPRGHRIJURZWKRIPLFUREHVLQFOXGLQJ VXEWOHGLIIHUHQFHVPD\JHQHUDWHDXQLTXHILQJHUSULQWIRU
RWLWLV PHGLD DQG F\VWLF ILEURVLV DQG GHQWDO GLVHDVHV HDFKLQGLYLGXDO+RZHYHUXQGHUFHUWDLQFRQGLWLRQV
VXFKDVGHQWDOFDULHVDQGSHULRGRQWDOGLVHDVH%LRILOP VKLIWV LQ WKH FRPSRVLWLRQ DQG SURSHUWLHV RI WKH GHQWDO
PLFUREHV GLVSOD\ SKHQRW\SLF FKDUDFWHUV WKDW DUH GUD SODTXH ELRILOP FRXOG OHDG WR GHQWDO GLVHDVHV VXFK DV
PDWLFDOO\GLIIHUHQWIURPWKHLUSODQNWRQLFFRXQWHUSDUWV GHQWDO FDULHV DQG SHULRGRQWDO GLVHDVHV ,W LV LPSRUWDQW
+LJKHUGUXJUHVLVWDQFHLVRQHRIWKHQRWDEOHIHDWXUHVRI WKDWFOLQLFLDQVDUHDZDUHRIDGYDQFHVLQWKHILHOGRIGHQ
WKH ELRILOP PRGH RI JURZWK %LRILOPV DUH VSDWLDOO\ WDOSODTXHELRILOPZKLFKFRXOGEHXVHGLQWKHGHYHORS
DUUDQJHG ZHOORUJDQLVHG PLFURELDO FRPPXQLWLHV WKDW PHQWRIQHZWUHDWPHQWRSWLRQVLQWKHIXWXUH7KHUHIRUH
GLVSOD\SURSHUWLHVDVDXQLW+HQFHELRILOPPLFURRUJDQ LQ WKLV EULHI UHYLHZ WKH SUHVHQW DXWKRUV H[DPLQH WKH
LVPV H[KLELW µVRFLDO¶ IHDWXUHV DV RSSRVHG WR WKH VXP VWUXFWXUH DQG SURSHUWLHV RI GHQWDO SODTXH ELRILOP DQG
RILQGLYLGXDOIHDWXUHVLQWKHFRPPXQLW\7KHUHIRUHDQ FULWLFDOO\ HYDOXDWH WKH G\QDPLF UHODWLRQVKLS EHWZHHQ
XQGHUVWDQGLQJ RI PLFURELDO ELRILOPV SURYLGHV XV ZLWK ELRILOPDQGKRVWLQWHUPVRIRUDOKHDOWKDQGGLVHDVH
DFOHDUHUYLHZRIWKHLUUROHLQRUDOKHDOWKDQGGLVHDVH 7KH DGKHUHQFH RI PLFUREHV WR DQ RUDO VXUIDFH LV D
SUHUHTXLVLWHIRUWKHIRUPDWLRQRIGHQWDOSODTXHELRILOP
+RZHYHU VLPSOH VXUIDFH FRQWDFW RU VHGLPHQWDWLRQ RI
)RUPDWLRQDQGVWUXFWXUHRIGHQWDOSODTXHELRILOP
PLFUREHV GRHV QRW OHDG WR WKH IRUPDWLRQ RI D ELRILOP
$OOVXUIDFHVRIWKHKXPDQERG\WKDWDUHH[SRVHGWRWKH ,QVWHDG D KLJKO\ RUJDQLVHG VHTXHQFH RI HYHQWV PXVW
H[WHULRUVXFKDVWKHRUDOFDYLW\VNLQDQGJDVWURLQWHVWLQDO RFFXU )LJ )LUVW SODQNWRQLF PLFURRUJDQLVPV
WUDFW DUH FRORQLVHG ZLWK UHVLGHQW PLFURELRWD +RZ DGKHUH WR WKH VXUIDFH 7KHQ PXOWLSOLFDWLRQ RI EDFWHU
HYHUHDFKRIWKHVHKDELWDWVKDUERXUVDXQLTXHJURXSRI LD OHDGV WR WKH IRUPDWLRQ RI GLVFUHWH FRORQLHV 7KHVH
PLFUREHVZLWKSURSHUWLHVWKDWDUHGLIIHUHQWIURPWKRVHRI PLFURFRORQLHVVHFUHWHH[WUDFHOOXODUSRO\PHULFVXEVWDQFH
WKHRWKHUKDELWDWV2UDOPLFURELRWDLVGLVWULEXWHGLQVWUDWL (36 LQ ZKLFK WKH\ EHFRPH HPEHGGHG UHVXOWLQJ LQ
ILHGVTXDPRXVRUDOPXFRVDOVXUIDFHVWRRWKVXUIDFHVDQG WKH GHYHORSPHQW RI ELRILOP (36 LV D GLVWLQFWLYH IHD
PXFRJLQJLYDOPDUJLQV WXUHVHHQLQPLFURELDOELRILOPDQGSURYLGHVDSK\VLFDO
'HQWDO SODTXH LV DQ DUFKHW\SLFDO ELRILOP FRPSRVHG VFDIIROG IRU WKH ELRILOP FRPPXQLW\ 0RUHRYHU (36
RI D FRPSOH[ PLFURELDO FRPPXQLW\7KH 1DWLRQDO DOVR FRQWDLQV ELRORJLFDOO\ DFWLYH FRPSRQHQWV VXFK DV
,QVWLWXWHVRI+HDOWKLQLWLDWHGWKH+XPDQ2UDO0LFURELRPH DQWLPLFURELDO HQ]\PHV WKDW SURWHFW WKH ELRILOP FRP
'DWDEDVH EDVHG RQ 6 U'1$ JHQH VHTXHQFLQJ WHFK PXQLW\DJDLQVWQR[LRXVHQYLURQPHQWDOVWLPXOL,QDODWHU
QLTXHV WR REWDLQ D KROLVWLF YLHZ RI WKH GHQWDO SODTXH VWDJHRIGHYHORSPHQWPLFURFRORQLHVHPEHGGHGLQ(36
E\WKHSUHVHQWDXWKRUVGLIIHUHQFHVLQWKHXOWUDVWUXFWXUH 6LPLODUO\WKHPHQDTXLQRQHSURGXFHGE\9HLOORQHOODDQG
DQG PRUSKRORJ\ RI WKH GHQWDO SODTXH ELRILOP ZHUH 3URSLRQLEDFWHULXPLVYLWDOIRUWKHV\QWKHVLVRIYLWDPLQ
IRXQGEHWZHHQµVORZSODTXHIRUPHUV¶DQGµIDVWSODTXH .ZKLFKSURPRWHVWKHJURZWKRIEDFWHULDVXFKDV3RU
IRUPHUV¶ 2WKHU VWXGLHV KDYH DOVR GHPRQVWUDWHG WKDW SK\URPRQDV3UHYRWHOODDQG%LILGREDFWHULXP$QRWKHU
FRQVLGHUDEOH YDULDWLRQ LQ GHQWDO SODTXH WKLFNQHVV FDQ H[DPSOHLVWKHXVHRIWKLDPLQHDQGLVREXW\UDWHE\VSLUR
EHVHHQZLWKLQLQGLYLGXDOV2QHVWXG\UHSRUWHGVLPLODU FKHWHVZKLFKLVSURGXFHGE\)XVREDFWHULXPVSHFLHVLQ
SODTXHWKLFNQHVVHVLQWKHEXFFDOUHJLRQRIWKHPD[LOOD WKHGHQWDOSODTXHELRILOP:HDUHRQO\EHJLQQLQJWRJDLQ
DQGPDQGLEOHEXWWKLQQHUELRILOPRQWKHSDODWDOVLGH DQXQGHUVWDQGLQJRIWKHIDVFLQDWLQJDQGLQWULJXLQJUHOD
'\QDPLF SURFHVVHV RI V\QHUJLVP DQG DQWDJRQLVP WLRQVKLSVDPRQJWKHPLFURELDOPHPEHUVRIGHQWDOSODTXH
RFFXUGXULQJGHYHORSPHQWEXWRQFHHVWDEOLVKHGGHQWDO ELRILOPZKLFKFRXOGFHUWDLQO\KHOSXVWRGHYLVHEHWWHU
SODTXHELRILOPLVFRQVLGHUHGWREHLQDVWDWHRIKRPHR VWUDWHJLHVIRUPRGXODWLQJWKHSODTXHELRILOPWRZDUGVD
VWDVLV 7KHUHIRUH PDWXUH GHQWDO SODTXH ELRILOP DFWV KHDOWK\VWDWH
DVDFRPPXQLW\RUDXQLWUDWKHUWKDQDVDVXPRIWKH $XQLTXHIHDWXUHUHODWHGWRPLFURELDOELRILOPLVKLJKHU
SURSHUWLHV RI LQGLYLGXDO EDFWHULDO PHPEHUV 0LFURELDO DQWLPLFURELDOUHVLVWDQFHDQGWKLVFDQEHVHHQLQGHQWDO
KRPHRVWDVLV RI WKH GHQWDO SODTXH LV RQO\ GLVWXUEHG LI SODTXHELRILOP7KHUHDUHVWXGLHVWKDWVKRZPLFUREHVLQ
GUDVWLFFKDQJHVRFFXULQWKHLPPHGLDWHHQYLURQPHQWRI WKHGHQWDOSODTXHELRILOPFRPPXQLW\DUHPRUHUHVLVWDQW
WKHKRVWVXFKDVFKDQJHVLQGLHWDU\LQWDNHRUFKDQJHV WR FRPPRQO\ XVHG DQWLPLFURELDO DJHQWV WKDQ DUH FRU
LQLPPXQLW\OHDGLQJWRLQYDVLRQRIKRVWWLVVXHVE\ELR UHVSRQGLQJSODQNWRQLFFRXQWHUSDUWV6HYHUDOK\SRWKHVHV
ILOP EDFWHULD7KLV LQLWLDWHV D SDWKRORJLFDO VHTXHODH RI KDYHEHHQSXWIRUZDUGWRH[SODLQWKHKLJKHUDQWLELRWLF
LQIHFWLRQ DQG FRQFXUUHQW KRVW LQIODPPDWRU\ UHVSRQVH UHVLVWDQFHRIPLFURELDOELRILOPVVXFKDVDOWHUHGPHWD
UHSUHVHQWLQJ D VKLIW IURP KHDOWK\ SODTXH ELRILOP WR D EROLFVWDWHFRQWULEXWLRQRIH[WUDFHOOXODUPDWUL[KLJKHU
µSDWKRJHQLFELRILOP¶3DWKRJHQLFGHQWDOSODTXHELRILOPV DQWLR[LGDWLYHFDSDFLWLHVGLIIHUHQWLDOWUDQVFULSWRPLFDQG
QRWRQO\UHVXOWLQGHQWDOGLVHDVHVVXFKDVGHQWDOFDULHV SURWHRPLFVH[SUHVVLRQDQGSUHVHQFHRIµVOHHSLQJFHOOV¶
DQGSHULRGRQWDOGLVHDVHEXWFRXOGDOVREHLQYROYHGLQ RU SHUVLVWHU FHOOV +RZHYHU WKH H[DFW PHFKDQLVP
GLVHDVHV LQ WKH FDUGLRYDVFXODU UHVSLUDWRU\ UHQDO DQG E\ZKLFKELRILOPPLFURRUJDQLVPVDFTXLUHKLJKHUDQWL
RWKHUV\VWHPV PLFURELDOUHVLVWDQFHUHPDLQVWREHHOXFLGDWHG
,Q YLYR VWXGLHV RI GHQWDO SODTXH KDYH FRUURERUDWHG
WKHVH LQ YLWUR REVHUYDWLRQV $ VWXG\ RQ VXEJLQJLYDO
3URSHUWLHVRIGHQWDOSODTXHELRILOP
ELRILOP VKRZHG WKDW WKH FRQFHQWUDWLRQ RI DQWLELRWLFV
2QH RI WKH LQWULJXLQJ IHDWXUHV RI PLFURELDO ELRILOP UHTXLUHGWRLQKLELWEDFWHULDLQVWHDG\VWDWHELRILOPFRXOG
LQFOXGLQJ GHQWDO SODTXH ELRILOP LV LWV VHOIVXVWDLQD EH XS WR WLPHV JUHDWHU WKDQ ZRXOG EH UHTXLUHG WR
ELOLW\$ PLFURELDO ELRILOP FRPPXQLW\ ZRXOG VXUYLYH LQKLELWWKHLUSODQNWRQLFPRGHRIJURZWK)XUWKHUPRUH
XQGHUKLJKO\FKDOOHQJLQJHQYLURQPHQWDOFRQGLWLRQVWKDW WKH DQWLELRWLFV WHWUDF\FOLQH GR[\F\FOLQH PLQRF\FOLQH
LWV SODQNWRQLF FRXQWHUSDUWV ZRXOG QRW )RU LQVWDQFH LW DPR[LFLOOLQ PHWURQLGD]ROH RU FRPELQDWLRQV VXFK DV
KDVEHHQVKRZQWKDWWKHELRILOPPRGHRIJURZWKDOORZV DPR[LFLOOLQFODYXODQDWH DQG DPR[LFLOOLQPHWURQLGD]ROH
PLFUREHVWRVXUYLYHXQGHUQXWULWLRQOLPLWHGFRQGLWLRQV ZHUH LQHIIHFWLYH LQ HUDGLFDWLQJ D GD\ROG PDWXUH
IRUDORQJSHULRGRIWLPH6LPLODUO\PLFURELDOFRQVWLWX GHQWDOSODTXHELRILOP$QRWKHUVWXG\VKRZHGWKDWLQ
HQWVRIWKHGHQWDOSODTXHELRILOPGRQRWUHO\RQWKHQXWUL ELRILOPSHULRGRQWDOSDWKRJHQ3JLQJLYDOLVFRXOGEH
WLRQWDNHQE\WKHKRVWWKH\DUHVXVWDLQHGE\HVWDEOLVKLQJ DQGWLPHVPRUHUHVLVWDQWWRGR[\F\FOLQHDQGPHWUR
µIRRGFKDLQV¶LQYROYLQJRWKHUPHPEHUVRIWKHFRPPX QLGD]ROHUHVSHFWLYHO\WKDQLWVSODQNWRQLFFRXQWHUSDUW
QLW\ *URZWK RI WKH GHQWDO SODTXH ELRILOP GHSHQGV RQ 0LVXVH RI WHWUDF\FOLQH PD\ HQULFK WKH EDFWHULD LQ WKH
WKH QXWULHQWV GHULYHG IURP HQGRJHQRXV VRXUFHV VXFK GHQWDOSODTXHZLWKEURDGUDQJHDQWLELRWLFUHVLVWDQFH
DV VDOLYD DQG JLQJLYDO FUHYLFXODU IOXLG UDWKHU WKDQ WKH 7KHVHVWXGLHVGHPRQVWUDWHWKHUHODWLYHODFNRIHIILFDF\
H[RJHQRXVIRRGLQWDNHRIWKHKRVW7KHUHIRUHDPHWD RIV\VWHPLFDQWLELRWLFWKHUDS\IRUSHULRGRQWDOGLVHDVHV
EROLFSURGXFWRIRQHRUJDQLVPPD\EHDQHVVHQWLDOSUL DQG HPSKDVLVH WKH QHHG IRU DOWHUQDWLYH PHWKRGV IRU
PDU\VRXUFHRIQXWULWLRQRIDQRWKHU)RULQVWDQFHDFLGR FRQWUROIRUGHQWDOSODTXHUHODWHGGLVHDVHV
JHQLFEDFWHULDVXFKDV6WUHSWRFRFFXV/DFWREDFLOOXVDQG 4XRUXP VHQVLQJ 46 RU µFRPPXQLFDWLRQ EHWZHHQ
$FWLQRP\FHV SURGXFH ODFWDWH DV D E\SURGXFW RI WKHLU EDFWHULD¶LVDQLQWULJXLQJSURSHUW\RIPLFURELDOELRILOPV
FDUERK\GUDWHPHWDEROLVP2WKHUEDFWHULDOVSHFLHVVXFK 46 ZRUNV DV D JDWHNHHSHU FRQWUROOLQJ WKH JURZWK RI
DV9HLOORQHOODDQG3URSLRQLEDFWHULXPXWLOLVHODFWDWHDV WKH PLFURELDO FRPPXQLW\ E\ VLJQDOOLQJ WR EDFWHULD WR
D FDUERQ VRXUFH DQG E\ GRLQJ VR FRQYHUW ODFWDWH LQWR OHDYHWKHELRILOPWRILQGQHZKDELWDWV46LVPHGLDWHG
ZHDNSURSLRQLFDFLGUHGXFLQJWKHULVNRIGHQWDOFDULHV E\ VPDOO PROHFXOHV VXFK DV FRPSHWHQFH VWLPXODWLQJ
GHQWDOFDULHV7KHUHIRUHRQHPXVWQRWEHFRQILQHGWR
WKHWUDGLWLRQDOWKLQNLQJWKDWDVLQJOHVSHFLHVLVWKHVROH
FDXVHRIGLVHDVHVVXFKDVGHQWDOFDULHV
5HFHQWDGYDQFHVLQWKHXQGHUVWDQGLQJRIWKHPROHFX
ODU PLFURELRORJ\ RI GHQWDO SODTXH ELRILOP KDYH SUR
GXFHG QXPHURXV FOLQLFDO EHQHILWV 2QH VXFK H[DPSOH
LV [\OLWRO ZKLFK VHOHFWLYHO\ LQKLELWV WKH JURZWK DQG
PHWDEROLVPRI6PXWDQV&OLQLFDOVWXGLHVKDYHVKRZQ
WKH LQFRUSRUDWLRQ RI [\OLWRO LQWR FKHZLQJ JXP WR EH
HIIHFWLYH LQ UHGXFLQJ PXWDQV VWUHSWRFRFFL DQG ORZHU
LQJGHQWDOFDULHV&RQYHUVHO\VRPHLQYLWURVWXGLHV
XVLQJ PXOWLVSHFLHV FDULRJHQLF ELRILOP PRGHOV KDYH
GHPRQVWUDWHGWKDW[\OLWRODQGVRUELWROPLJKWQRWEHDV
Fig 2 Scanning electron micrograph showing mature Can- HIIHFWLYHDVFODLPHG8VHRISURELRWLFEDFWHULDVXFKDV
dida albicans biofilm. /DFWREDFLOOXV UKDPQRVXV /% DV D PLON VXSSOHPHQW
LV DQRWKHU LGHD WKDW KDV EHHQ SURSRVHG IRU FRQWUROOLQJ
GHQWDO FDULHV +RZHYHU VRPH VWXGLHV KDYH VKRZQ
WKDW WKH ELRILOP PRGH RI JURZWK KDV JUHDWHU WROHUDQFH WKLV PLJKW QRW EH HIIHFWLYH LQ FRQWUROOLQJ FRORQLVDWLRQ
RIDFLGLFVWUHVVZKLFKFRXOGEHDVKLJKDVVL[RUGHUVRI RIFDULRJHQLFEDFWHULDLQWKHFDULHVDFWLYHDGROHVFHQW
PDJQLWXGH KLJKHU FRPSDUHG ZLWK WKH SODQNWRQLF IRUP 2WKHUVWUDWHJLHVKDYHEHHQFRQVLGHUHGVXFKDVWKHXVH
RIEDFWHULD0DWXUH 6PXWDQVELRILOPGRZQUHJXODWHV RI SURWHDVH SURGXFHG E\ HDUO\ GHQWDO SODTXH ELRILOP
WKHPDLQHQHUJ\JHQHUDWLQJJO\FRO\WLFSDWKZD\LQRUGHU FRORQLVHUV WR LQKLELW WKH FRORQLVDWLRQ RI 6 PXWDQV
WREHDFLGWROHUDQW7KHUHLVRWKHUHYLGHQFHWRVXJJHVW +RZHYHUWKHFRPSOHWHSLFWXUHRIWKHGHQWDOSODTXHELR
WKDWPHPEHUVRIWKHGHQWDOSODTXHELRILOPFRPPXQLW\ ILOPLVVWLOOQRWIXOO\XQGHUVWRRGZKLFKLVWKH$FKLOOHV¶
XQGHUJRSKHQRW\SLFFKDQJHVGXULQJKHDOWKDQGGLVHDVH KHHOLQWKHWDVNRIILQGLQJDVXFFHVVIXOVROXWLRQWRWKH
5HFHQWVWXGLHVVKRZHGWKDW 6PXWDQVVWUDLQVUHFRYHUHG JOREDOHSLGHPLFRIGHQWDOFDULHV
IURPFDULHVDFWLYHDQGFDULHVIUHHLQGLYLGXDOVGLIIHULQ
VHQVLWLYLW\WRKRVWDQWLPLFURELDOSHSWLGHV*HQHVDVVRFL
'HQWDOSODTXHELRILOPLQSHULRGRQWDOGLVHDVH
DWHGZLWKJOXFDQ*WIDQGIUXFWDQIWIKDYHEHHQVKRZQ
WR EH GLIIHUHQWLDOO\ H[SUHVVHG EHWZHHQ WKH SODQNWRQLF 7KH PDLQ IHDWXUH RI SHULRGRQWDO GLVHDVH LV LQIODPPD
DQGELRILOPEDFWHULD7KHHFRORJLFDOFKDQJHVWKDWRFFXU WLRQ RI WKH SHULRGRQWDO WLVVXHV LQ UHVSRQVH WR *UDP
LQWKHGHQWDOSODTXHELRILOPPD\WKHUHIRUHFRQWULEXWHWR QHJDWLYHSDWKRJHQLFEDFWHULDVXFKDV3JLQJLYDOLVDQG
WKHGLVHDVHSURFHVVVHHQLQGHQWDOFDULHV VSLURFKHWHVVXFKDV7GHQWLFRODLQWKHGHQWDOSODTXHELR
&RQYHUVHO\ VRPH VWXGLHV KDYH VXJJHVWHG WKDW WKH ILOP$FFRUGLQJWRWKHHFRORJLFDOSODTXHK\SRWKHVLVLW
SUHVHQFH RI KLJK QXPEHUV RI 6 PXWDQV LQ WKH GHQWDO LVDVVXPHGWKDWVHFUHWLRQRIJLQJLYDOFUHYLFXODUIOXLGLV
SODTXH LV QRW VXIILFLHQW IRU WKH GHYHORSPHQW RI GHQWDO LQFUHDVHGLQUHVSRQVHWRLQIODPPDWLRQRIWKHSHULRGRQWDO
FDULHV7KHUHIRUH LW LV DVVXPHG WKDW WKH SUHVHQFH RI D WLVVXHV7KLV OHDGV WR D ULVH LQ WKH ORFDO S+ DERYH WKH
VLQJOHVSHFLHVDORQHLVQRWWKHLQLWLDWLQJIDFWRUEXWWKDW QRUPDOQHXWUDOYDOXH,WKDVEHHQVXJJHVWHGWKDWHYHQD
PXOWLSOHFDULRJHQLFVSHFLHVVXFKDV6PXWDQV6PLWLV PLQRUULVHLQS+DOORZVSHULRGRQWRSDWKLFEDFWHULDVXFK
5RWKLD$FWLQRP\FHV/DFWREDFLOOXVDQG%LILGREDFWHULXP DV 3 JLQJLYDOLV WR RYHUJURZ DQG RYHUULGH RWKHU PLFUR
EDFWHULDDQGHYHQIXQJDOVSHFLHVOLNH&DQGLGD)LJ RUJDQLVPVLQWKHGHQWDOSODTXH3RUSK\URPRQDVJLQJL
FRXOG DFFRXQW IRU D ELRILOP EHFRPLQJ FDULRJHQLF YDOLVLVDKHPLQGHSHQGHQWEDFWHULXPWKDWDFTXLUHVKHPLQ
,QWHUHVWLQJO\IXQJDOVSHFLHVVXFKDV&DQGLGDDOELFDQV IURP JLQJLYDO FUHYLFXODU IOXLG 6HFUHWRU\ SURWHDVH
KDYH EHHQ VKRZQ WR EH FDSDEOH RI FDXVLQJ RFFOXVDO KHPDJJOXWLQLQV VXFK DV JLQJLSDLQV KHPDJJOXWLQLQ %
FDULHVDWDKLJKUDWHLQUDWV$UHFHQWVWXG\ZKLFKXVHG DQGKHPDJJOXWLQLQ&DOVRDLG3JLQJLYDOLVLQDFTXLULQJ
LQVLWXLPDJLQJWHFKQLTXHVWRH[DPLQHWKHDUFKLWHFWXUH KHPLQIURPHU\WKURF\WHV$ULVHLQORFDOKHPLQFRQFHQ
RI WKH GHQWDO SODTXH ELRILOP RQ QDWXUDO WHHWK GHPRQ WUDWLRQGXHWRLQFUHDVHGJLQJLYDOFUHYLFXODUIOXLGGXULQJ
VWUDWHGWKDW&DOELFDQVFRXOGIRUPFRUQFREVWUXFWXUHV SHULRGRQWLWLV SURYLGHV D FRPSHWLWLYH DGYDQWDJH WR WKH
ZLWKVWUHSWRFRFFDOVSHFLHVLQWKHVXSUDJLQJLYDOSODTXH VRFDOOHGUHGFRPSOH[EDFWHULDLQFOXGLQJ3JLQJLYDOLV
ZKLFK PD\ H[SODLQ LWV LPSRUWDQW QLFKH LQ WKH GHQWDO RYHU RWKHU FRPPHQVDO EDFWHULD ,QWHUHVWLQJO\ UHFHQW
SODTXH 7DQQHU HW DO VXJJHVWHG 6FDUGRYLD ZLJJVLDH VWXGLHVKDYHVKRZQWKDW3JLQJLYDOLVLVDEOHWRVKLIWLWV
D QHZ FDULRJHQLF EDFWHULD FRXOG EH DVVRFLDWHG ZLWK OLSRSRO\VDFFKDULGH/36VWUXFWXUHIURPSHQWDDF\ODWHG
+DQQLJ 0 -RLQHU$ 7KH VWUXFWXUH IXQFWLRQ DQG SURSHUWLHV RI WKH ELRILOPIRUPDWLRQE\6WUHSWRFRFFXVPXWDQV2UDO0LFURELRO,PPXQRO
DFTXLUHGSHOOLFOH0RQRJU2UDO6FL± ±
2NDKDVKL11DNDWD07HUDR<HWDO3LOLRIRUDO6WUHSWRFRFFXVVDQ 'L[RQ'5%DLQEULGJH%:'DUYHDX530RGXODWLRQRIWKHLQQDWH
JXLQLVELQGWRVDOLYDU\DP\ODVHDQGSURPRWHWKHELRILOPIRUPDWLRQ LPPXQH UHVSRQVH ZLWKLQ WKH SHULRGRQWLXP 3HULRGRQWRO
0LFURE3DWKRJ± ±
=LMQJH9YDQ/HHXZHQ0%'HJHQHU-(HWDO2UDOELRILOPDUFKLWHF 0DUVK3'$UHGHQWDOGLVHDVHVH[DPSOHVRIHFRORJLFDOFDWDVWURSKHV"
WXUHRQQDWXUDOWHHWK3/R62QHH 0LFURELRORJ\±
%ULQLJ 00 /HSS 3: 2XYHUQH\ &&$UPLWDJH *& 5HOPDQ '$ 3DUDKLWL\DZD1%-LQ/-/HXQJ:.<DP:&6DPDUDQD\DNH/3
3UHYDOHQFH RI EDFWHULD RI GLYLVLRQ 70 LQ KXPDQ VXEJLQJLYDO 0LFURELRORJ\RIRGRQWRJHQLFEDFWHUHPLD%H\RQGHQGRFDUGLWLV&OLQ
SODTXH DQG WKHLU DVVRFLDWLRQ ZLWK GLVHDVH$SSO (QYLURQ 0LFURELRO 0LFURELRO5HY±
± 0DUVK3'0LFURELRORJ\RIGHQWDOSODTXHELRILOPVDQGWKHLUUROHLQ
3DVWHU%-%RFKHV6.*DOYLQ-/HWDO%DFWHULDOGLYHUVLW\LQKXPDQ RUDOKHDOWKDQGFDULHV'HQW&OLQ1RUWK$P±
VXEJLQJLYDOSODTXH-%DFWHULRO± :HOLQ1HLODQGV - 6YHQVDWHU *$FLG WROHUDQFH RI ELRILOP FHOOV RI
/RZ%/HH:6HQHYLUDWQH&-6DPDUDQD\DNH/3+DJJ88OWUDVWUXF 6WUHSWRFRFFXVPXWDQV$SSO(QYLURQ0LFURELRO±
WXUHDQGPRUSKRORJ\RIELRILOPVRQWKHUPRSODVWLFRUWKRGRQWLFDSSOL .OLQNH7*XJJHQKHLP%.OLPP:7KXUQKHHU7'HQWDOFDULHVLQ
DQFHV LQ ³IDVW´ DQG ³VORZ´ SODTXH IRUPHUV (XU - 2UWKRG UDWVDVVRFLDWHGZLWK&DQGLGDDOELFDQV&DULHV5HV±
± 7DQQHU$&0DWKQH\-0.HQW5/HWDO&XOWLYDEOHDQDHURELFPLFUR
$XVFKLOO70+HOOZLJ(6FXOHDQ$+HLQ1$UZHLOHU1%,PSDFWRI ELRWD RI VHYHUH HDUO\ FKLOGKRRG FDULHV - &OLQ 0LFURELRO
WKHLQWUDRUDOORFDWLRQRQWKHUDWHRIELRILOPJURZWK&OLQ2UDO,QYHVWLJ ±
± +ROJHUVRQ 3/ 6MRVWURP , 6WHFNVHQ%OLFNV & 7ZHWPDQ 6 'HQWDO
+RMR.1DJDRND62KVKLPD70DHGD1%DFWHULDOLQWHUDFWLRQVLQ SODTXHIRUPDWLRQDQGVDOLYDU\PXWDQVVWUHSWRFRFFLLQVFKRROFKLOGUHQ
GHQWDOELRILOPGHYHORSPHQW-'HQW5HV± DIWHU XVH RI [\OLWROFRQWDLQLQJ FKHZLQJ JXP ,QW - 3DHGLDWU 'HQW
0DK7)2
7RROH*$0HFKDQLVPVRIELRILOPUHVLVWDQFHWRDQWLPLFUR ±
ELDODJHQWV7UHQGV0LFURELRO± 6RGHUOLQJ(+LUYRQHQ$.DUMDODLQHQ6HWDO7KHHIIHFWRI[\OLWRORQ
/HZLV.5LGGOHRIELRILOPUHVLVWDQFH$QWLPLFURE$JHQWV&KHPRWKHU WKHFRPSRVLWLRQRIWKHRUDOIORUD$SLORWVWXG\(XU-'HQW
± ±
6HQHYLUDWQH&-:DQJ<-LQ/$ELNR<6DPDUDQD\DNH/3&DQGLGD *LHUWVHQ($UWKXU5$*XJJHQKHLP%(IIHFWVRI[\OLWRORQVXUYLYDO
DOELFDQVELRILOPIRUPDWLRQLVDVVRFLDWHGZLWKLQFUHDVHGDQWLR[LGDWLYH RIPXWDQVVWUHSWRFRFFLLQPL[HGVL[VSHFLHVLQYLWURELRILOPVPRGHO
FDSDFLWLHV3URWHRPLFV± OLQJVXSUDJLQJLYDOSODTXH&DULHV5HV±
6HGODFHN0-:DONHU&$QWLELRWLFUHVLVWDQFHLQDQLQYLWURVXEJLQJL 3HWHUVVRQ /* 0DJQXVVRQ . +DNHVWDP 8 %DLJL$ 7ZHWPDQ 6
YDOELRILOPPRGHO2UDO0LFURELRO,PPXQRO± 5HYHUVDO RI SULPDU\ URRW FDULHV OHVLRQV DIWHU GDLO\ LQWDNH RI PLON
/DUVHQ76XVFHSWLELOLW\RI3RUSK\URPRQDVJLQJLYDOLVLQELRILOPVWR VXSSOHPHQWHGZLWKIOXRULGHDQGSURELRWLFODFWREDFLOOLLQROGHUDGXOWV
DPR[LFLOOLQGR[\F\FOLQHDQGPHWURQLGD]ROH2UDO0LFURELRO,PPX $FWD2GRQWRO6FDQG0D\>(SXEDKHDGRISULQW@
QRO± /H[QHU 02 %ORPTYLVW 6 'DKOHQ *7ZHWPDQ 6 0LFURELRORJLFDO
5HDG\ ' 5REHUWV$3 3UDWWHQ - HW DO &RPSRVLWLRQ DQG DQWLELRWLF SURILOHVLQVDOLYDDQGVXSUDJLQJLYDOSODTXHIURPFDULHVDFWLYHDGR
UHVLVWDQFHSURILOHRIPLFURFRVPGHQWDOSODTXHVEHIRUHDQGDIWHUH[SR OHVFHQWV EHIRUH DQG DIWHU D VKRUWWHUP GDLO\ LQWDNH RI PLON VXSSOH
VXUHWRWHWUDF\FOLQH-$QWLPLFURE&KHPRWKHU± PHQWHGZLWKSURELRWLFEDFWHULD±DSLORWVWXG\2UDO+HDOWK3UHY'HQW
/D]DU94XRUXPVHQVLQJLQELRILOPV+RZWRGHVWUR\WKHEDFWHULDO ±
FLWDGHOVRUWKHLUFRKHVLRQSRZHU"$QDHUREH$SU>(SXEDKHDG :DQJ%<'HXWFK$+RQJ-.XUDPLWVX+.3URWHDVHVRIDQHDUO\
RISULQW@ FRORQL]HU FDQ KLQGHU 6WUHSWRFRFFXV PXWDQV FRORQL]DWLRQ LQ YLWUR -
-DNXERYLFV167DONRIWKHWRZQ,QWHUVSHFLHVFRPPXQLFDWLRQLQRUDO 'HQW5HV±
ELRILOPV0RO2UDO0LFURELRO± 3LKOVWURP%/0LFKDORZLF]%6-RKQVRQ1:3HULRGRQWDOGLVHDVHV
0DUVK 3' 'HQWDO SODTXH DV D PLFURELDO ELRILOP &DULHV 5HV /DQFHW±
± 0DUVK3'0LFURELDOHFRORJ\RIGHQWDOSODTXHDQGLWVVLJQLILFDQFHLQ
-DNXERYLFV16.ROHQEUDQGHU3(7KHURDGWRUXLQ7KHIRUPDWLRQRI KHDOWKDQGGLVHDVH$GY'HQW5HV±
GLVHDVHDVVRFLDWHGRUDOELRILOPV2UDO'LV± *HQFR&$5HJXODWLRQRIKHPLQDQGLURQWUDQVSRUWLQ3RUSK\URPRQDV
5LFNDUG$+3DOPHU5--U%OHKHUW'6HWDO$XWRLQGXFHU$FRQ JLQJLYDOLV$GY'HQW5HV±
FHQWUDWLRQGHSHQGHQWVLJQDOIRUPXWXDOLVWLFEDFWHULDOELRILOPJURZWK $O4XWXE01%UDKDP3+.DULPL1DVHU/0HWDO+HPLQGHSHQG
0RO0LFURELRO± HQWPRGXODWLRQRIWKHOLSLG$VWUXFWXUHRI3RUSK\URPRQDVJLQJLYDOLV
+DQQDQ65HDG\'-DVQL$6HWDO7UDQVIHURIDQWLELRWLFUHVLVWDQFH OLSRSRO\VDFFKDULGH,QIHFW,PPXQ±
E\WUDQVIRUPDWLRQZLWKH'1$ZLWKLQRUDOELRILOPV)(06,PPXQRO 'DUYHDX533HULRGRQWLWLV$SRO\PLFURELDOGLVUXSWLRQRIKRVWKRPHR
0HG0LFURELRO± VWDVLV1DW5HY0LFURELRO±
0HW]JHU=%ODVEDOJ-'RWDQ0:HLVV(,(QKDQFHGDWWDFKPHQWRI %DJDLWNDU-'HPXWK'5'DHS&$HWDO7REDFFRXSUHJXODWHV3JLQ
3RUSK\URPRQDVJLQJLYDOLVWRKXPDQILEUREODVWVPHGLDWHGE\)XVR JLYDOLVILPEULDOSURWHLQVZKLFKLQGXFH7/5K\SRVHQVLWLYLW\3/R6
EDFWHULXPQXFOHDWXP-(QGRG± 2QHH
0HW]JHU=%ODVEDOJ-'RWDQ07VHVLV,:HLVV(,&KDUDFWHUL]D 6KFKLSNRYD$<1DJDUDMD+1.XPDU366XEJLQJLYDOPLFURELDOSUR
WLRQRIFRDJJUHJDWLRQRI)XVREDFWHULXPQXFOHDWXP3.ZLWKVL[ ILOHVRIVPRNHUVZLWKSHULRGRQWLWLV-'HQW5HV±
3RUSK\URPRQDVJLQJLYDOLVVWUDLQV-(QGRG± +DIIDMHH$'6RFUDQVN\665HODWLRQVKLSRIFLJDUHWWHVPRNLQJWRWKH
0HW]JHU=/LQ<<'LPHR)HWDO6\QHUJLVWLFSDWKRJHQLFLW\RI3RU VXEJLQJLYDOPLFURELRWD-&OLQ3HULRGRQWRO±
SK\URPRQDVJLQJLYDOLVDQG)XVREDFWHULXPQXFOHDWXPLQWKHPRXVH 8]HO 1*7HOHV )57HOHV 53 HW DO 0LFURELDO VKLIWV GXULQJ GHQWDO
VXEFXWDQHRXVFKDPEHUPRGHO-(QGRG± ELRILOPUHGHYHORSPHQWLQWKHDEVHQFHRIRUDOK\JLHQHLQSHULRGRQWDO
0DUVK3'0RWHU$'HYLQH'$'HQWDOSODTXHELRILOPV&RPPXQL KHDOWKDQGGLVHDVH-&OLQ3HULRGRQWRO±
WLHVFRQIOLFWDQGFRQWURO3HULRGRQWRO± 'UHVFKHU-6FKODIHU66FKDXGLQQ&HWDO0ROHFXODUHSLGHPLRORJ\
7DPXUD6<RQH]DZD+0RWHJL0HWDO,QKLELWLQJHIIHFWVRI6WUHS DQGVSDWLDOGLVWULEXWLRQRI6HOHQRPRQDVVSSLQVXEJLQJLYDOELRILOPV
WRFRFFXV VDOLYDULXV RQ FRPSHWHQFHVWLPXODWLQJ SHSWLGHGHSHQGHQW (XU-2UDO6FL±