Cyclic Di-GMP Stimulates Biofilm Formation and Inhibits Virulence of Francisella novicida

dc.contributor.authorZogaj, Xhavit
dc.contributor.authorWyatt, Geoff C.
dc.contributor.authorKlose, Karl E.
dc.date.accessioned2023-06-30T17:56:21Z
dc.date.available2023-06-30T17:56:21Z
dc.date.issued2012-11-12
dc.description.abstractFrancisella tularensis is a Gram-negative bacterium that is highly virulent in humans, causing the disease tularemia. F. novicida is closely related to F. tularensis and exhibits high virulence in mice, but it is avirulent in healthy humans. An F. novicida-specific gene cluster (FTN0451 to FTN0456) encodes two proteins with diguanylate cyclase (DGC) and phosphodiesterase (PDE) domains that modulate the synthesis and degradation of cyclic di-GMP (cdGMP). No DGC- or PDE-encoding protein genes are present in the F. tularensis genome. F. novicida strains lacking either the two DGC/PDE genes (cdgA and cdgB) or the entire gene cluster (strain KKF457) are defective for biofilm formation. In addition, expression of CdgB or a heterologous DGC in strain KKF457 stimulated F. novicida biofilms, even in a strain lacking the biofilm regulator QseB. Genetic evidence suggests that CdgA is predominantly a PDE, while CdgB is predominantly a DGC. The F. novicida qseB strain showed reduced cdgA and cdgB transcript levels, demonstrating an F. novicida biofilm signaling cascade that controls cdGMP levels. Interestingly, KKF457 with elevated cdGMP levels exhibited a decrease in intramacrophage replication and virulence in mice, as well as increased growth yields and biofilm formation in vitro. Microarray analyses revealed that cdGMP stimulated the transcription of a chitinase (ChiB) known to contribute to biofilm formation. Our results indicate that elevated cdGMP in F. novicida stimulates biofilm formation and inhibits virulence. We suggest that differences in human virulence between F. novicida and F. tularensis may be due in part to the absence of cdGMP signaling in F. tularensis.en_US
dc.description.departmentMolecular Microbiology and Immunologyen_US
dc.description.sponsorshipNational Institutes of Healthen_US
dc.identifier.citationZogaj, X., Wyatt, G. C., & Klose, K. E. (2012). Cyclic Di-GMP Stimulates Biofilm Formation and Inhibits Virulence of Francisella novicida. Infection and Immunity, 80(12), 4239-4247. doi:10.1128/iai.00702-12en_US
dc.identifier.issn1098-5522
dc.identifier.otherhttps://doi.org/10.1128/iai.00702-12
dc.identifier.urihttps://hdl.handle.net/20.500.12588/1968
dc.language.isoen_USen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.ispartofseriesInfection and Immunity;Vol. 80, No. 12
dc.subjectFrancisellaen_US
dc.subjectFrancisella novicidaen_US
dc.titleCyclic Di-GMP Stimulates Biofilm Formation and Inhibits Virulence of Francisella novicidaen_US
dc.typeArticleen_US

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