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.

Public Health Relevance

Bacteriathatcolonizeanimalstransitionfromanenvironmentallifestyletothehost-associatedstate,inwhich individualbacterialcellscoordinatefunctionstoactasagroup.Usingamodelsystemthatallowsfor interrogationofbacteriadirectlywithintheanimalhost,thisprojectaddresseshowmolecularsignalingfromthe hostdirectsthebacteriatoformbiofilms,matrix-encodedgroupsofcellsthatarewidespreadandoften underlieantimicrobialresistance.Informationinthemodelwillthenbeusedtoimprovebeneficialbacterial colonization(e.g.probiotics)andinterferewithcolonizationbypathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM119627-05
Application #
9700153
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Sledjeski, Darren D
Project Start
2016-09-01
Project End
2021-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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