Abstract: The present invention relates to compositions comprising EbpA and methods of use thereof. Specifically, methods useful in the treatment and prevention of EbpA-associated infections.

Abstract: The present invention relates to compositions comprising EbpA and methods of use thereof. Specifically, methods useful in the treatment and prevention of EbpA-associated infections.

Abstract: The present invention relates to compositions comprising EbpA and methods of use thereof. Specifically, methods useful in the treatment and prevention of EbpA-associated infections.

Abstract: The present invention relates to compositions comprising EbpA and methods of use thereof. Specifically, methods useful in the treatment and prevention of EbpA-associated infections.

Abstract: Novel amino methylated 2-pyridinones, precursors, intermediates, and derivatives; the methods for the preparation of the same; uses of the same for inhibiting pili formation in bacteria; and pharmaceutical compositions comprising these compounds are described in this application. The present compounds may be employed to inhibit biofilm formation and thereby inhibit adherence of bacteria to a host cell.

Abstract: Novel amino methylated 2-pyridinones, precursors, intermediates, and derivatives; the methods for the preparation of the same; uses of the same for inhibiting pili formation in bacteria; and pharmaceutical compositions comprising these compounds are described in this application. The present compounds may be employed to inhibit biofilm formation and thereby inhibit adherence of bacteria to a host cell.

Abstract: Novel amino methylated 2-pyridinones, precursors, intermediates, and derivatives; the methods for the preparation of the same; uses of the same for inhibiting pili formation in bacteria; and pharmaceutical compositions comprising these compounds are described in this application. The present compounds may be employed to inhibit biofilm formation and thereby inhibit adherence of bacteria to a host cell.

Abstract: Many Gram-negative pathogens assemble adhesive pili structures on their surfaces that allow them to colonize host tissues and cause disease. The present invention relates to novel compounds that mimic a chaperone G1 beta-strand or an amino terminal motif of a pilus subunit. The present invention also relates to the complex formed from the binding of such mimic compounds to the hydrophobic groove of a pilus subunit. Competitively interacting with the binding site of pili subunits will negatively affect the chaperone/usher pathway, which is one molecular mechanism by which Gram-negative bacteria assemble adhesive pili structures, and thus prevent or inhibit pilus assembly.

Abstract: A protein construct comprising a pilus protein portion, preferably a structurally stabilized pilus-protein, and an additional, or effector, portion other than a pilus protein or chaperone and wherein said effector portion serves to stabilize the pilus protein portion and to confer a therapeutic activity, such as vaccine activity or anti-microbial or anticancer activity, on the protein construct is disclosed. Such effector portion commonly comprises a donor strand complementary segment capable of structurally stabilizing a pilus protein subunit and attaching the auxiliary portion to said subunit to form the pilus protein analog of the invention. Methods of using said protein constructs are also disclosed as well as the formation and use of analogs comprising fragments of a pilus protein linked to effector components to produce immunogenic and/or therapeutic activity.

Abstract: Novel pyridinones and their derivatives which are effective in treating or preventing Gram-negative bacterial infections are provided. The pyridinones are stable and easily derivatized; the methods by which these derivatizations occur is described. Two regioselective and functional group tolerant methods for the synthesis of the novel pyridinones are also provided. One such synthetic method involves reacting an imine and a Meldrum's acid derivative in solution. The other synthetic method is a solid phase synthesis of the pyridinones in which an imine is prepared bound to a solid support and a Meldrum's acid derivative is reacted with the imine. Novel imine intermediates useful in the solid phase and solution methods of synthesizing the pyridionones are also described.

Abstract: The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. It particularly relates to the vaccination of mammalian species, especially human patients, with variants of the E. coli FimCH protein that elicit antibodies that have better functional inhibitory activity than antibodies raised against wild type protein. In particular, such variants include mutations that promote a more open confirmation of the FimH protein, particularly in regions involved in mannose binding, to expose regions previously poorly exposed and mutations that abolish a significantly reduce mannose binding. In another aspect, the invention provides antibodies against such proteins and protein complexes that may be used in passive immunization to protect or treat pathogenic bacterial infections.

Abstract: The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. It particularly relates to the vaccination of mammalian species with heteropolymeric protein complexes as a mechanism for stimulating production of antibodies that protect the vaccine recipient against infection by pathogenic bacterial species. In another aspect the invention provides antibodies against such proteins and protein complexes that may be used as diagnostics and/or as protective/treatment agents for pathogenic bacterial species. A novel vector for expressing the FimC-H complex at optimal levels is also disclosed.

Abstract: The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. It particularly relates to the vaccination of mammalian species with heteropolymeric protein complexes as a mechanism for stimulating production of antibodies that protect the vaccine recipient against infection by pathogenic bacterial species. In another aspect the invention provides antibodies against such proteins and protein complexes that may be used as diagnostics and/or as protective/treatment agents for pathogenic bacterial species. A novel vector for expressing the FimC-H complex at optimal levels is also disclosed.

Abstract: Compounds of the formula and the salts, esters and amides thereof wherein Z is S, SO, SO2 or O; each of R1, R2 and R3 is independently H or substituted or unsubstituted alkyl (1-10C), substituted or unsubstituted alkenyl, substituted or unsubstituted acyl (2-11C), substituted or unsubstituted aryl (6-14C), substituted or unsubstituted arylcarbonyl (7-15C), substituted or unsubstituted arylalkyl (7-15C), substituted or unsubstituted pyridyl wherein substituents on any alkyl, alkenyl, or acyl moiety are selected from the group consisting of halo, and RO, wherein R is H or alkyl (1-6C), and substituents on any aryl or pyridyl moiety are selected from the group consisting of halo, and RO, where R is H or alkyl (1-6C), —CN and —CF3; with the proviso that R1 is not H and R1 and R3 are not identical and with the proviso that in formula (1), the B ring may contain one double bond that is located between positions 2 and 3, and in formula (2), the B ring may contain one double bond tha

Abstract: A protein construct comprising a pilus protein portion, preferably a structurally stabilized pilus-protein, and an additional, or effector, portion other than a pilus protein or chaperone and wherein said effector portion serves to stabilize the pilus protein portion and to confer a therapeutic activity, such as vaccine activity or anti-microbial or anticancer activity, on the protein construct is disclosed. Such effector portion commonly comprises a donor strand complementary segment capable of structurally stabilizing a pilus protein subunit and attaching the auxiliary portion to said subunit to form the pilus protein analog of the invention. Methods of using said protein constructs are also disclosed as well as the formation and use of analogs comprising fragments of a pilus protein linked to effector components to produce immunogenic and/or therapeutic activity.

Abstract: The DegP (HtrA) protease is a multifunctional protein essential for the removal of misfolded and aggregated proteins in the periplasm. The present invention provides an assay for inhibitors of DegP activity, comprising mixing a suspected inhibitor of DegP activity with DegP and a suitable substrate (preferably a native substrate of DegP such as PapA) and detecting changes in DegP activity. DegP has been shown to be essential for virulence in several Gram negative pathogens. Only three natural targets for DegP have been described: colicin A lysis protein (Cal), pilin subunits (K88, K99, Pap) and recently HMW1 and HMW2 from Hemophilus influenzae. In vitro, DegP has shown weak protease activity on casein and several other non-native substrates. The present inventors have identified the major pilin subunit of the Pap pilus, PapA, as a native DegP substrate and demonstrated binding and proteolysis of this substrate in vitro.