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Bordetella respiratory infections are common in people (B. pertussis) and in animals (B. bronchiseptica). During the last two decades, much has been learned about the virulence determinants, pathogenesis, and immunity of Bordetella. Clinically, the full spectrum of disease due to B. pertussis infection is now understood, and infections in adolescents and(More)
Many bacterial pathogens use the type III secretion system to inject "effector" proteins into host cells. Here, we report the identification of a 24 member effector protein family found in pathogens including Salmonella, Shigella, and enteropathogenic E. coli. Members of this family subvert host cell function by mimicking the signaling properties of(More)
Lafora disease (LD) is a progressive myoclonic epilepsy resulting in severe neurodegeneration followed by death. A hallmark of LD is the accumulation of insoluble polyglucosans called Lafora bodies (LBs). LD is caused by mutations in the gene encoding the phosphatase laforin, which reportedly exists solely in vertebrates. We utilized a bioinformatics screen(More)
The BvgAS virulence control system regulates the expression of type III secretion genes in Bordetella subspecies that infect humans and other mammals. We have identified five open reading frames, btrS, btrU, btrX, btrW and btrV, that are activated by BvgAS and encode regulatory factors that control type III secretion at the levels of transcription, protein(More)
Bordetella bronchiseptica utilizes a type III secretion system (TTSS) for induction of non-apoptotic cytotoxicity in host cells and modulation of host immunity. The identity of Bordetella TTSS effectors, however, has remained elusive. Here we report a genome-wide screen for TTSS effectors based on shared biophysical and functional characteristics of class I(More)
We show that the secreted antigen, IbpA, of the respiratory pathogen Histophilus somni induces cytotoxicity in mammalian cells via its Fic domains. Fic domains are defined by a core HPFxxGNGR motif and are conserved from bacteria to humans. We demonstrate that the Fic domains of IbpA catalyze a unique reversible adenylylation event that uses ATP to add an(More)
The Fic family of adenylyltransferases, defined by a core HPFx(D/E)GN(G/K)R motif, consists of over 2,700 proteins found in organisms from bacteria to humans. The immunoglobulin-binding protein A (IbpA) from the bacterial pathogen Histophilus somni contains two Fic domains that adenylylate the switch1 tyrosine residue of Rho-family GTPases, allowing the(More)
The maintenance of endoplasmic reticulum (ER) homeostasis is a critical aspect of determining cell fate and requires a properly functioning unfolded protein response (UPR). We have discovered a previously unknown role of a post-translational modification termed adenylylation/AMPylation in regulating signal transduction events during UPR induction. A family(More)
We have recently described a multicomponent cascade that regulates type III secretion in Bordetella. This cascade includes a group of proteins, BtrU, BtrW, and BtrV, that contain an array of domains that define partner-switching complexes previously characterized in gram-positive bacteria. BtrU contains a PP2C-like serine phosphatase domain, BtrW contains a(More)
Type III secretion system (T3SS) tip complexes serve as adaptors that bridge the T3SS needle and the pore-forming translocation apparatus. In this report we demonstrate that Bsp22, the most abundantly secreted substrate of the Bordetella T3SS, self-polymerizes to form the Bordetella bronchiseptica tip complex. Bsp22 is required for both T3SS-mediated(More)