A systems analysis of the AHL Quorum Sensing system in Pseudomonas aeruginosa

Se s o ules wi h inpu ec o sModules Quo um sensing is a cell densi y dependen gene egula ion sys em whe eby popula ions o bac e ia communica e h ough small di usible signalling molecules in o de o coo dina e he exp ession o speci ic genes such as i ulence ac o s depending on he hei numbe s, exhibi ing popula ion-le el beha iou .1 In obio icsIn obio ics F ancisco J. Rome o-Campe o1, Jona han Blakes1, Miguel Cáma a2, Na alio K asnogo 1 1ASAP Resea ch G oup, School o Compu e Science and IT, Uni e si y o No ingham, Jubilee Campus, No ingham, NG8 1BB, UK. { xc, j b,nxk}@cs.no .ac.uk 2The Pseudomonas Quo um Sensing G oup, Ins i u e o In ec ion, Immuni y and In lamma ion & School o Molecula Medical Sciences, Cen e o Biomolecula Sciences, Uni e si y o No ingham. miguel.cama a@no ingham.ac.uk A sys ems analysis o he AHL Quo um Sensing sys em in Pseudomonas ae uginosa Funded by EPSRC & BBSRC g an s EP/E017215/1& BB/F01855X/1 a → b [ ]label a2b3c Mul ise s o objec sPopula ion o molecules Memb anesCompa men s Rew i ing ules on objec s Molecula in e ac ions P sys em speci ica ion Biological en i y c high cell densi ylow cell densi y di ision & quo a ion ais ans o med in o bwi h a e c Name({molecules,...}{cons an s,...}{labels}) Quo um sensing elies on he syn hesis, accumula ion and subsequen sensing o hese signals, pa icula ly N-acylhomose ine lac ones (AHLs) in P. ae uginosa: Composing a quo um sensing module In ou me hodology a module is a se o ules ha de ine a in eg a ed biological unc ion, such as un egula ed gene exp ession consis ing o p oduc ion and deg ada ion o he LasR p o ein om gene lasR: Modules can be assembled in o la ge modules. He e a LasI UnReg module, enzyma ic 3OC12 syn hesis and di usion, complexa ion and posi i e gene egula ion modules a e composed in o he quo um sensing module QS({LasR,...,RsaL·lasI},{c1,...,c24},{b}) = signalling molecule bac e ia In mos QS sys ems he signals, S, a e syn hesised by an Ienzyme encoded by a geneI. A ecep o p o ein Rencoded by a geneR in e ac s wi h S o o m an ac i e ansc ip ion ac o R·Swhich binds o geneI ampli ying he p oduc ion o Ip o ein and he e o e syn hesis o S. This ansc ip ion ac o also egula es many o he genes. N H O O N-bu y yl homose ine lac one (C4) N H OO O N-3-oxo-dodecanoyl homose ine lac one (3OC12) O O • Vi ulence • Seconda y Me aboli es • Mo ili y and Swa ming • Conjuga ion • Bio ilm De elopmen • G ow h Inhibi ion i + R S In P. ae uginosa LasR s imula es LasI, and RsaL which sup esses LasI. This ensu es he apid bu con olled p oduc ion o AHL- syn hesis equi ed o coo dina e a popula ion pheno ype. Re e ences 1. Be na dini F, Gheo ghe M, K asnogo N. Quo um sensing P sys ems. Theo . Compu . Sci. 371(1-2): 20-33 (2007) 2. Rome o Campe o FJ. & Pé ez Jiménez MJ. Modelling gene exp ession con ol using P sys ems: The Lac Ope on, a case s udy 3. Alon U. Ne wo k mo i s: heo y and expe imen al app oaches. Na u e Re iews Gene ics 8 (2007) BioSys ems 91 (2008) When coupled o a nega i e gene egula ion module h ough lasI a 3OC12 con olled ype 1 incohe en eed- o wa d loop3eme ges. Modelling quo um sensing he e o e equi es a colony-le el iew wi h many indi idual copies o he same quo um sensing gene ne wo k in di e en s a es. O dina y di e en ial equa ions a e p oblema ic o modelling gene ne wo ks, as low numbe s o molecules dec ease he signal o noise a io due o he ini e numbe e ec (η~ 1/√N). P sys ems ep esen a no el disc e e, s ochas ic and mesoscopic amewo k o modelling cellula sys ems2 ha acili a es he assembly o ansc ip ional modules, mass duplica ion o cells and ealis ic kine ics using he well-s udied Gillespie algo i hm, o he obse a ion o eme gen beha iou s h ough simula ion. A P sys em consis s o a nes ed memb ane s uc u e (colonies, cells o in acellula compa men s), con aining mul ise s o objec s (genes, complexes, me aboli es) which a e ew i en by ules ( eac ions). LasR RsaL LasI + − +speed up by LasR·3OC12 homeos asis by RsaL ype 1 IFFL • G ow h Inhibi ion IR R S+ s’ S