Theobjectiveofmylaboratoryistocharacterizehowmolecularcommunicationbetweenbacteriaandtheir animalhostsleadstospecificandreproduciblecolonization.Toaccomplishthisgoal,thelaboratorystudiesthe V.fischeri-squidsystem.Thissystemisadvantageousbecausebacteriacolonizethroughthenaturalrouteof infection,allanimalsarecolonizedwithinthreehoursofbacterialinoculationintotheseawater,thebacteria canbesubjecttodetailedgeneticmanipulation,andtheprecisesiteofinfectioncanbeimageddirectlyinthe liveanimalhost,allowingforcuttingedgegeneticandgenomicapproaches.Focusingonhowsquidare reproduciblycolonizedbythespecificsymbiont,totheexclusionofthemillionsofcompetingbacteriain seawater,hasrevealedkeyrolesforbacterialaggregationandbiofilmformationinpromotingspecifichost- microbeinteractions.Recentlyourglobalgeneticscreentoidentifycolonizationfactorsrevealedmultiplenovel biofilmactivatorsandidentifiedanorphanhistidinekinase,whichactsasanegativeregulatorofSypbiofilm developmentinvivo.Toelucidatethepathwaysgoverningcolonizationandbiofilmdevelopmentintheanimal hostwewill(1)dissectthemoleculardetailsofthenovelhistidinekinasepathway,(2)defineathightemporal andspatialresolutionthestepsnecessaryfortheestablishmentofthismutualisticrelationship,and(3) characterizetheroleofnewcolonizationfactorsusinggeneticandmetabolomicapproaches.Sincethe strategiesusedbyV.fischeritointeractwithitshostareconservedinotherhost-microbesystems,ourfindings willbeapplicabletounderstandotherbeneficialassociationsaswellasinteractionsbetweenpathogenic bacteriaandtheirhosts.
Bacteriathatcolonizeanimalstransitionfromanenvironmentallifestyletothehost-associatedstate,inwhich individualbacterialcellscoordinatefunctionstoactasagroup.Usingamodelsystemthatallowsfor interrogationofbacteriadirectlywithintheanimalhost,thisprojectaddresseshowmolecularsignalingfromthe hostdirectsthebacteriatoformbiofilms,matrix-encodedgroupsofcellsthatarewidespreadandoften underlieantimicrobialresistance.Informationinthemodelwillthenbeusedtoimprovebeneficialbacterial colonization(e.g.probiotics)andinterferewithcolonizationbypathogens.
| Mandel, Mark J (2018) D-fining DarR: a LysR-type transcriptional regulator that responds to D-aspartate. J Bacteriol : |
| Thompson, Cecilia M; Tischler, Alice H; Tarnowski, Denise A et al. (2018) Nitric oxide inhibits biofilm formation by Vibrio fischeri via the nitric oxide sensor HnoX. Mol Microbiol : |
| Speare, Lauren; Cecere, Andrew G; Guckes, Kirsten R et al. (2018) Bacterial symbionts use a type VI secretion system to eliminate competitors in their natural host. Proc Natl Acad Sci U S A 115:E8528-E8537 |
| Henry, Christopher S; Rotman, Ella; Lathem, Wyndham W et al. (2017) Generation and Validation of the iKp1289 Metabolic Model for Klebsiella pneumoniae KPPR1. J Infect Dis 215:S37-S43 |
| Mandel, Mark J; Dunn, Anne K (2016) Impact and Influence of the Natural Vibrio-Squid Symbiosis in Understanding Bacterial-Animal Interactions. Front Microbiol 7:1982 |
