Abstract: A novel sarR gene and sarR gene product which down regulates the expression of sarA and the resulting virulence determinants in Staphylococcus aureus is provided. Methods for modulating the expression of sarA and virulence determinants are also provided. A preferred embodiment of the present invention provides structural information relating to the gene product and enables the identification and formulation of lead compounds and reducements for treating and preventing infections by S. aureus and related bacteria.

Abstract: There is disclosed vaccines formulated for administration to the mucosa of the lungs of a mammal, and the use thereof in methods for prophylaxis or treatment of an infection by at least one pathogenic microorganism. The vaccines comprise a cellular fraction of the microorganism that is essentially free of particulate matter and includes polyvalent soluble antigen from the microorganism.

Abstract: The present invention relates to methods and compositions for treatment of microbial infections and for the enhancement of resistance to infection. The invention comprises administration of an effective amount of bacterial lysate compositions for the treatment of pathological conditions of microbial infections. The present invention can also be used to enhance the immune system to prevent infections by the administration of an effective amount of the compositions.

Abstract: The present invention relates to a method of producing recombinant modified Staphylococcal toxin having improved stability, comprising the steps of preparing a modified toxin in which a specific amino acid sequence is substituted and a vector for expressing the modified toxin, and culturing E. coli transformed with the vector, and a use thereof for the vaccine.

Abstract: The invention provides isolated polypeptide and nucleic acid sequences derived from Staphylococcus epidermidis that are useful in diagnosis and therapy of pathological conditions; antibodies against the polypeptides; and methods for the production of the polypeptides. The invention also provides methods for the detection, prevention and treatment of pathological conditions resulting from bacterial infection.

Abstract: The present invention encompasses protective monoclonal antibodies that bind to peptidoglycan of Gram-positive bacteria. The antibodies also bind to whole bacteria and enhance phagocytosis and killing of the bacteria in vitro and block nasal colonization by Gram-positive bacteria in vivo. The invention also provides human, humanized and chimeric antibodies. The invention also sets forth the heavy chain and light chain variable regions of an antibody within the invention.

Abstract: A method of immunomodulating the T cell response in Staphylococcal bacteria is provided wherein an effective amount of the Map protein from Staphylococcus aureus is administered to a host to prevent or suppress the T cell response. The present method may be utilized with either the Map protein or an effective subdomain or fragment thereof such as the Map 10 or Map 19 protein. The present invention is advantageous in that suppression or prevention of the T cell response in a host can prevent or ameliorate a wide variety of the pathogenic conditions such as T cell lymphoproliferative disease and toxic shock syndrome wherein the overstimulation of T cells needs to be suppressed or modulated.

Abstract: Monoclonal antibodies which can bind to the Fnbp protein of Staphylococcus aureus and which are generated from a peptide from the D2 region of fibronectin binding protein B (Fnbp) of S. aureus are provided which can be useful in the treatment and protection against infection from staphylococcal bacteria such as Staphylococcus aureus. The monoclonal antibodies of the invention are advantageous in that they bind S. aureus in high affinity and thus can be useful in the prevention of the adherence of staph bacteria to host cells by impairing or inhibiting the ability of S. aureus Fnbp to bind to fibronectin. Kits and methods of utilizing the monoclonal antibodies of the invention are also provided.

Abstract: This invention relates to compositions and methods which provide protection against, or reduce the severity of toxic shock and septic shock from bacterial infections. More particularly it relates to peptides derived from homologous sequences of the family of staphylococcal and streptococcal toxins, which may be polymeric, and carrier-conjugates thereof. The invention also relates to serum antibodies induced by the peptides and carrier-conjugates and their use to prevent, treat, or protect against the toxic effects of most, if not all, of the staphylococcal and streptococcal toxins. The invention also relates to diagnostic assays and kits to detect the presence of staphylococcal and streptococcal toxins, or antibodies thereto. The invention also relates isolated and purified to nucleic acids encoding the peptides of the invention and transformed host cells containing those nucleic acids.

Abstract: A substantially pure capsular exopolysaccharide adhesin of coagulase-negative staphylococcal strains, and a gonoral method to prepare such adhesins, are described. Vaccines composed of such adhesins, and uses of such adhesins to produce polyclonal and monoclonal antibodies against such adhesins, are also disclosed. The adhesins are useful in coating polymoric medical materials to prevent colonization by coagulase-negative staphylococcal strains, and as a probe in selecting desirable polymeric medical materials. Such adhesin antibodies are useful in vivo to prevent infection by nosocomial coagulase-negative staphylococcal strains, in assays for the detection of such bacteria, in assays for the estimation of such adhesins in complex mixtures, and as an affinity chromatography matrix.

Abstract: A novel vaccine for immunizing animals against Staphylococcus aureus-induced mastitis is disclosed. The vaccine is comprised of whole killed cells of S. aureus in a dosage effective to immunize an animal against the organism, in combination with a pharmaceutically acceptable carrier.

Abstract: Monoclonal antibodies which can bind to the ClfA protein and which are generated from binding subdomains or active fragments of the ClfA protein from Staphylococcus aureus, including the active fragments proteins from its fibrinogen binding domain such as Clf40 protein, the Clf33 protein, or ClfA N3, are provided which can be useful in the treatment and protection against infection from staphylococcal bacteria such as Staphylococcus aureus. In addition, medical instruments can be treated using the monoclonal antibodies of the invention in order to reduce or eliminate the possibility of their becoming infected or further spreading the infection. In particular, the antibodies of the present invention are advantageous because they can prevent adherence of the bacteria to host cells by impairing or inhibiting the ability of S. aureus ClfA to bind to fibrinogen or fibrin, and thus can be utilized in methods or treating or preventing staphylococcal inventions.

Abstract: A series of genes from Streptococcus pyogenes are shown to encode products which are implicated in virulence. The identification of these genes therefore allows attenuated microorganisms to be produced. Furthermore, the genes or their encoded products can be used in the manufacture of vaccines for therapeutic application.

Abstract: Purified, host-specific, non-toxic, wide host range and virulent bacteriophage preparations that are effective in killing bacterial organisms in vivo are disclosed. Also disclosed are compositions containing these bacteriophages, methods of making the bacteriophage preparations and methods of treating bacterial infections using the compositions. Methods of treating bacterial infections using the compositions containing the bacteriophages in combination with conventional antibiotics also are disclosed.

Abstract: A negatively-charged Staphylococcus antigen contains amino acids and a N-acetylated hexosamine as a major carbohydrate component. The antigen is common to many coagulase-negative strains of Staphylococcus, including S. epidermidis, S. haemolyticus, and S. hominis. Staphylococcus strains that carry the antigen include many clinically significant strains of Staphylococcus. The antigen and antibodies to the antigen are useful in kits and assays for diagnosing Staphylococcus infection. Vaccines of the antigen and of whole cells that carry the antigen also are disclosed.

Abstract: The present invention relates to methods and compositions for treatment of microbial infections and for the enhancement of resistance to infection. The invention comprises administration of an effective amount of bacterial lysate compositions for the treatment of pathological conditions of microbial infections. The present invention can also be used to enhance the immune system to prevent infections by the administration of an effective amount of the compositions.

Abstract: This invention is directed to mutant SPE-A toxins or fragments thereof, vaccine and pharmaceutical compositions, and methods of using the vaccine and pharmaceutical compositions. The preferred SPE-A toxin has at least one amino acid change and is substantially non-lethal compared with the wild type SPE-A toxin. The mutant SPE-A toxins can form vaccine compositions useful to protect animals against the biological activities of wild type SPE-A toxin.

Abstract: The invention features incapacitated whole cell bacterial immunogenic compositions produced by infecting a bacterium with Lys minus bacteriophage, which are deficient in the lysin protein. Lys minus bacteriophage retain activity in infection of its appropriate bacterial host, destruction of the bacterial genome, and replication, which are sufficient to inhibit bacterial growth and replication. The resulting, Lys minus-infected bacterium is provided in a state of bacteriostasis, and is not capable of replicating further (e.g., is “incapacitated”). The incapacitated bacterium can then be used as to elicit an immune response for prophylactic and/or therapeutic purposes. The invention thus also features incapacitated bacteria formulated appropriately for use in immunogenic compositions for eliciting an immune response, e.g., for production of antibodies in a non-human host or in a whole cell bacterial vaccine.

Abstract: Methods for the identification, production and use of staphylokinase derivatives characterized by a reduced immunogenicity after administration in patients. The derivatives of the invention are obtained by preparing a DNA fragment comprising at least the part of the coding sequence of staphylokinase that provides for its biological activity; performing in vitro site-directed mutagenesis on the DNA fragment to replace one or more codons for wild-type amino acids by a codon for another amino acid; cloning the mutated DNA fragment in a suitable vector; transforming or transfecting a suitable host cell with the vector; culturing the host cell under conditions suitable for expressing the DNA fragment; and purifying the expressed staphylokinase derivative to homogeneity. Preferably the DNA fragment is a 453 bp EcoRI-HindIII fragment of the plasmid pMEX602sakB, (pMEX.

Abstract: Pyrogenic toxins, such as staphylococcal enterotoxins, modified in the disulfide loop region are provided. The modified toxins retain useful biological properties but have substantially reduced toxicity compared to the corresponding unmodified native toxin. The native pyrogenic toxins are typically modified by deletions within the disulfide loop region to produce modified enterotoxins having 100-fold or greater decrease in toxicity.

Abstract: The invention is directed to isolated polypeptides bearing sequence homology to the Sp36 protein found in pneumococcal organisms, such as Streptococcus pneumoniae. Polynucleotides encoding such polypeptides are also disclosed. The invention also relates to antibodies specific for the disclosed polypeptides and to uses of such antibodies in the treatment of diseases caused by staphylococci as well as group A and B streptococci. In addition, the invention relates to the use of the disclosed polypeptides in compositions and as vaccines and for prophylactic uses such as in vaccination of animals, especially humans, against a wide variety of streptococcal, staphylococcal and other diseases.

Abstract: Isolated peptide sequences and proteins containing these sequences are provided which are useful in the prevention and treatment of infection caused by Gram-positive bacteria. The peptide sequences have been shown to be highly conserved motifs in the surface proteins of Gram-positive bacteria, and these consensus sequences include amino acid sequences such as LPXTG (SEQ ID NO:13), ALKTGKIDIIISGMTSTPERKK (SEQ ID NO:14), VEGAWEKPVAEAYLKQN (SEQ ID NO:15), and EYAGVDIDLAKKIAK (SEQ ID NO:16). By virtue of the highly conserved regions, the sequences and the proteins including these sequences can be utilized to generate antibodies which can recognize these highly conserved motifs and the proteins containing them and thus be useful in the treatment or prevention of a wide range of infections caused by Gram-positive bacteria.

Abstract: The present invention is a substantially purified sortase-transamidase enzyme from Gram-positive bacteria, such as Staphylococcus aureus.

Abstract: Isolated and purified Staphylococcus thioredoxin reductases (TrxB) are provided. Polynucleotides encoding the TrxBs, vectors and host cells containing such polynucleotides are also provided. In addition, antibodies reactive with the TrxBs are provided, as are methods of isolating the TrxBs, as well as methods for producing recombinant TrxBs, using TrxBs for screening compounds for TrxB-modulating activity, and detecting Staphylococcus in a test sample.

Abstract: A substantially pure capsular exopolysaccharide adhesin of coagulaso-negative staphylococcal strains, and a general method to prepare such adhesins, are described. Vaccines composed of such adhesins, and uses of such adhesins to produce polyclonal and mono-clonal antibodies against such adhesins, are also disclosed. The adhesins are useful in coating polymeric medical materials to prevent colonization by coagulase-negative staphylococcal strains, and as a probe in selecting desirable polymeric medical materials. Such adhesin antibodies are useful in vivo to prevent infection by noso-comial coagulase-negative staphylococcal strains, in assays for the detection of such bacteria, in assays for the estimation of such adhesins in complex mixtures, and as an affinity chromatography matrix.

Abstract: A new fibrinogen binding protein or polypeptide originating from coagulase negative staphylococci, biotechnological methods for producing the protein or polypeptide having fibrinogen binding activity and a recombinant DNA molecule coding for the protein (or fragments thereof), and micro-organisms (including viruses) containing this recombinant DNA molecule. The present invention further comprises the therapeutic and diagnostic use of the protein and/or DNA, e.g., a diagnostic kit for determining the presence and/or type of coagulase negative staphylococci and a vaccine composition, comprising the protein or DNA.

Abstract: The present invention involves a method and an immuno-analytical device for the rapid and simultaneous detection of multiple micro-organisms in the biological fluids from milk-producing animals suffering from mastitis. This method is based on a lateral flow immuno-assay technique performed to detect antigens specific for multiple infectious agents which are known to cause and/or be encountered in cases of mastitis. Mastitis is an inflammatory condition affecting the udders of milk-producing animals as a result of microbial infections.

Abstract: Multicomponent vaccines are provided which aid in the prevention and treatment of staphylococcal infections and which include certain selected combinations of bacterial binding proteins or fragments thereof, or antibodies to those proteins or fragments. By careful selection of the proteins, fragments, or antibodies, a vaccine is provided that imparts protection against a broad spectrum of Staphylococcus bacterial strains and against proteins that are expressed at different stages of the logarithmic growth curve. In one embodiment of the invention, a composition is provided that includes at least a collagen binding protein or peptide (or an appropriate site directed mutated sequence thereof) such as CNA, or a protein or fragment with sufficiently high homology thereto, in combination with a fibrinogen binding protein, preferably Clumping factor A (“ClfA”) or Clumping factor B (“ClfB”), or a useful fragment thereof or a protein or fragment with sufficiently high homology thereto.

Abstract: Biologically active polypeptides and/or antigens are delivered by administering to a subject a non-invasive or non-pathogenic bacterium which expresses one or more antigens or polypeptides. The non-invasive or non-pathogenic bacterium can be included in delivery systems or pharmaceutical formulations.

Abstract: This invention discloses immunopotentiating agents which stimulate an immune resposne. These agents are categorized into single agents that act directly, adjuvants added concurrently with the agents, or heteroconjugates. Heteroconjugate agents eleicit or enhance a cellular or humoral immune response which may be specific for an epitope contained within an amino acid sequence. Enhanced hematopoieses by bone marrow stem cell recruitment was also a result of administering some of these agents.

Abstract: The present invention relates to methods and compositions for treatment of microbial infections and for the enhancement of resistance to infection. The invention comprises administration of an effective amount of bacterial lysate compositions for the treatment of pathological conditions of microbial infections. The present invention can also be used to enhance the immune system to prevent infections by the administration of an effective amount of the compositions.

Abstract: Isolated polynucleotide molecules contain a nucleotide sequence that encodes a L. intracellularis HtrA, PonA, HypC, LysS, YcfW, ABC1, or Omp100 protein, a substantial portion of the sequences, or a homologous sequence. Related polypeptides, immunogenic compositions and assays are described.

Abstract: Biologically active polypeptides and/or antigens are delivered by administering to a subject a non-invasive or non-pathogenic bacterium which expresses one or more antigens or polypeptides. The non-invasive or non-pathogenic bacterium can be included in delivery systems or pharmaceutical formulations.

Abstract: Staphylococcal and Enterrococcal glycoconjugate vaccines are disclosed for use in preventing or treating bacterial infection in an immune-compromised individual. Such vaccines contain an immunocarrier and a conjugate of a polysaccharide or glycopeptide surface antigen from a clinically-significant bacterial strain. The vaccines can be used for active protection in immune-compromised individuals who are to be subjected to conditions that place them at immediate risk of developing a bacterial infection, as would be case in the context of a catheterization or a surgical procedure.

Abstract: The invention provides antigenic compositions for the vaccination of an animal against bovine mastitis caused by infection with Staphylococcus aureus. The invention also provides methods for stimulating an animal's immune system to respond to antigens derived from selected strains of Staphylococcus aureus by administering the antigenic compositions of the invention to the animal.

Abstract: A negatively-charged S. aureus antigen contains &bgr;-hexosamine as a major carbohydrate component. S. aureus strains that carry the antigen account for nearly all of the clinically significant strains of S. aureus that are not Type 5 or Type 8 strains. The antigen can be used in combination with S. aureus Type 5 polysaccharide antigen and S. aureus Type 8 polysaccharide antigen to provide nearly 100% coverage of S. aureus infection. The antigen and antibodies to the antigen are useful in kits and assays for diagnosing S. aureus infection. A whole cell vaccine of cells that contain the antigen is particularly useful in the treatment of mastitis.

Abstract: A rapid, simple, and inexpensive sandwich enzyme-linked receptor based immunodot assay detects pathogens or pathogenic products in test samples using receptors for a characteristic component of the pathogen. This assay is widely applicable because it is highly specific, it does not require special equipment, and the results can be obtained within a few hours with the naked eye. Since the lipid-based receptors have a long-shelf life, they can be easily stored and used for a long time.

Abstract: The invention relates to immunomodulatory effective microbiological compositions, to methods for the production thereof and to their use. The inventive microbiological immuno modulators are suited for use in active and passive immunization. The inventive compositions are primarily used as homeopathic medications in the areas of cardiac and circulatory disorders, hypertension or allergic ailments. The immunomodulatory effective microbiological compositions are comprised of equal parts of antigen and antitoxin suspensions and are potentiated using a potentiating solution.

Abstract: A method for the laboratory determination of prosthetic infections is described. This method, performed on biological fluids isolated from patients, is based on the detection of antibodies specific for the polysaccharides produced by bacteria colonizing prosthetic devices.

Abstract: The invention provides Fibronectin Binding Protein polypeptides and DNA (RNA) encoding Fibronectin Binding Protein polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing Fibronectin Binding Protein polypeptides to screen for antibacterial compounds.

Abstract: This invention provides peptides which inhibit agr transcription in S. aureus and thereby block the expression of virulence factors in S. aureus, pharmaceutical compositions comprising these peptides, as well as methods for treating or preventing an infection or disease caused by S. aureus using the peptides of the present invention.

Abstract: Polymers and polymer conjugates comprising crosslinked Staphylococcal protein A, or crosslinked protein A-superantigen, or crosslinked functional derivatives thereof ranging in size from 12kDa to 1O,OOOkDa are useful in the treatment of autoimmune diseases, such as rheumatoid arthritis and ITP as well as neoplastic diseases. Compositions and pharmaceutical composition comprising chemically crosslinked polymers of protein A alone or protein A and bacterial enterotoxins, optionally further complexed with immunoglobulins and complement components, are disclosed, as are methods for making and using these compositions in the treatment of diseases. Plasma perfusates of protein A immunadsorbent columns in clinical use are shown to act through the leaching of polymers of protein A and protein A-Staphylococcal enterotoxin B having a broad range of molecular masses.

Abstract: spsA polypeptides and DNA (RNA) encoding such spsA and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such spsA for the treatment of infection, particularly bacterial infections. Antagonists against such spsA and their use as a therapeutic to treat infections, particularly bacterial infections are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to the presence of spsA nucleic acid sequences and the polypeptides in a host. Also disclosed are diagnostic assays for detecting polynucleotides encoding spsA and for detecting the polypeptide in a host.

Abstract: The invention provides Def1 polypeptides and DNA (RNA) encoding Def1 polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing Def1 polypeptides to screen for antibacterial compounds.

Abstract: spsA polypeptides and DNA (RNA) encoding such spsA and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such spsA for the treatment of infection, particularly bacterial infections. Antagonists against such spsA and their use as a therapeutic to treat infections, particularly bacterial infections are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to the presence of spsA nucleic acid sequences and the polypeptides in a host. Also disclosed are diagnostic assays for detecting polynucleotides encoding spsA and for detecting the polypeptide in a host.

Abstract: A substantially pure capsular exopolysaccharide adhesin of coagulase-negative staphylococcal strains, and a general method to prepare such adhesins, are described. Vaccines composed of such adhesins, and uses of such adhesins to produce polyclonal and monoclonal antibodies against such adhesins, are also disclosed. The adhesins are useful in coating polymeric medical materials to prevent colonization by coagulase-negative staphylococcal strains, and as a probe in selecting desirable polymeric medical materials. Such adhesin antibodies are useful in vivo to prevent infection by nosocomial coagulase-negative staphylococcal strains, in assays for the detection of such bacteria, in assays for the estimation of such adhesins in complex mixtures, and as an affinity chromatography matrix.

Abstract: An antigenic composition is derived from surface extracted protein of cell wall surfaces and the culture supernatant extract of Staphylococci. The strain is highly virulent and &bgr; hemolytic on blood agar plate. They are mixed and purified by ion exchange and gel filtration column chromatography. This preparation method can be used in all Gram-positive bacilli. The antigens, having molecular weight of about 10,000-70,000 are certain kinds of glycoprotein comprising proteins (ca. 10-20%) and carbohydrates (ca. 75-90%). They are extracted from the cells with the use of a hypertonic buffer solution of pH 6.5-8.5 at a temperature below the denaturing point of the antigenic protein, and are salted out with ammonium sulfate (ca. 65-85%). The culture supernatant is extracted in the same way by salting out with ammonium sulfate (ca. 65-85%). The antigen fraction from both cell wall and culture supernatant is obtained in such an operation. The antigen can be used as a preparation antigen to Staphylococcus antigen.

Abstract: Methods for the identification, production and use of staphylokinase derivatives characterized by a reduced immunogenicity after administration in patients. The derivatives of the invention are obtained by preparing a DNA fragment comprising at least the part of the coding sequence of staphylokinase that provides for its biological activity; performing in vitro site-directed mutagenesis on the DNA fragment to replace one or more codons for wild-type amino acids by a codon for another amino acid; cloning the mutated DNA fragment in a suitable vector; transforming or transfecting a suitable host cell with the vector; culturing the host cell under conditions suitable for expressing the DNA fragment; and purifying the expressed staphylokinase derivative to homogeneity. Preferably the DNA fragment is a 453 bp EcoRI-HindIII fragment of the plasmid pMEX602sakB, (pMEX.

Abstract: spo-rel polypeptides and DNA (RNA) encoding such spo-rel and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such spo-rel for the treatment of infection, particularly bacterial infections. Antagonists against such spo-rel and their use as a therapeutic to treat infections, particularly bacterial infections are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to the presence of spo-rel nucleic acid sequences and the polypeptides in a host. Also disclosed are diagnostic assays for detecting polynucleotides encoding the relA/spoT gene family and for detecting the polypeptide in a host.

Abstract: A negatively-charged S. aureus antigen contains &bgr;-hexosamine as a major carbohydrate component. S. aureus strains that carry the antigen account for nearly all of the clinically significant strains of S. aureus that are not Type 5 or Type 8 strains. The antigen can be used in combination with S. aureus Type 5 polysaccharide antigen and S. aureus Type 8 polysaccharide antigen to provide nearly 100% coverage of S. aureus infection. The antigen and antibodies to the antigen are useful in kits and assays for diagnosing S. aureus infection. A whole cell vaccine of cells that contain the antigen is particularly useful in the treatment of mastitis.