Abstract
The development of effective strategies to combat biofilm infections by means of either mechanical or chemical approaches could dramatically change today’s treatment procedures for the benefit of thousands of patients. Remarkably, considering the increased focus on biofilms in general, there has still not been invented and/or developed any simple, efficient and reliable methods with which to “chemically” eradicate biofilm infections. This underlines the resilience of infective agents present as biofilms and it further emphasizes the insufficiency of today’s approaches used to combat chronic infections. A potential method for biofilm dismantling is chemical interception of regulatory processes that are specifically involved in the biofilm mode of life. In particular, bacterial cell to cell signaling called “Quorum Sensing” together with intracellular signaling by bis-(3′-5′)-cyclic-dimeric guanosine monophosphate (cyclic-di-GMP) have gained a lot of attention over the last two decades. More recently, regulatory processes governed by two component regulatory systems and small non-coding RNAs have been increasingly investigated. Here, we review novel findings and potentials of using small molecules to target and modulate these regulatory processes in the bacterium Pseudomonas aeruginosa to decrease its pathogenic potential.
Highlights
Over the years, research has provided increased insight into the mode of life of bacteria, in turn presenting important challenges in the treatment of infectious diseases
Targeting the biofilm and virulence without killing the bacteria has gained considerable attention as an anti-pathogenic strategy [14] and the present review turns to such investigations regarding small compounds capable of inhibiting cellular regulatory systems like, the Quorum Sensing (QS) systems (i.e., QS inhibitors (QSIs)), c-di-GMP as well as the Gac/Rsm cascade in P. aeruginosa from both natural and synthetic sources
It has been generally accepted that the formation of biofilms in the host organism correlates with the development of chronic infections [16]
Summary
Research has provided increased insight into the mode of life of bacteria, in turn presenting important challenges in the treatment of infectious diseases. Increased knowledge of essential regulatory systems involved in the biofilm life-cycle has culminated in the awareness of the possibility of attenuating bacteria’s biofilm developing capacity This reduces bacterial resilience and makes them more susceptible to subsequent combinatorial antibiotic treatments including the antimicrobial activities of the innate immune system. Targeting the biofilm and virulence without killing the bacteria has gained considerable attention as an anti-pathogenic strategy [14] and the present review turns to such investigations regarding small compounds capable of inhibiting cellular regulatory systems like, the QS systems (i.e., QSIs), c-di-GMP as well as the Gac/Rsm cascade in P. aeruginosa from both natural and synthetic sources. StSrtuructcuturersesofofthtehenantiavteivseigsniganl aml omleocluelceusleosf QofS;Q3S-;ox3o-o-Cxo1-2C-H12S-LH, SCL4,-HC4S-LH, SPLQ,SP, QHSH, QHHanQd aIQndS oIfQPS. aoefruPg.inaoesraugasinwoseallaass twheellinatesrnthalesiignntearlnmalolseicgunlaelc-mdoi-lGecMuPleocf-Gdir-aGmM-nPegoaftivGerabmac-tneergiaatainvde bparcetdeircitaedansedcopnrdeadriyctestdrucsetucorensdgareynersatrtuedctuurseisnggMenFeOraLteDd (musuilntgipleMfFoOldL)D(ht(tmp:u//lmtipfoleld.fronlda.)alb(hatntpy.: /e/dmu/f?oql=dm.rnfoal.da/lbRaNnAy.-eFdould/i?nqg=-mFofromld)/[R15N]Ao-fFtohledinnogn--Fcoordmin)g[1re5g] uolaf tothrey snmonal-lcoRdNinAgs rResgmuYlataonrdy RsmsmalZl RinNvAolsveRdsminY atnhde RGsamcZ/Rsinmvolcvaesdcadine thfreoGmacP/.Rsamerucgaisncoasdae afrnodm PP.. afeloruurgeisncoesnacea.nd3-oP.xofl-oCu1re2s-cHenScLe:. 3N-o-(x3o-o-Cxo12d-oHdSeLca: nNy-o(3l)--oLx-ohdoomdoescearninyeol)-lLa-chtoomneo,serCin4e-HlaScLto: neN, C-b4u-HtaSnLo:yNlh-obmutoasneoryinlheomlaocsteorninee, laHctHonQe:, H2-HheQp:ty2l--h4e-phtyydl-r4o-xhyyqdurionxoyliqnuei,noPliQneS,:PQ2S-h: e2p-htyelp-t3y-hl-y3d-hryodxyro-4x-yg-u4-ingoulionnoelo, neI,QISQ:S: 22--((--hhyyddrrooxxyypphheennyyll))-tthhiiaazzoollee--44--ccaarrbbaallddeehhyyddee,,cc--ddii--GGMMPP::bbisis-(-3(3-′-55′))--ccyycclliicc--ddiimmeerricicgguuaannoossinineemmoonnoopphhoospsphhaatete
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