Abstract: RNAIII inhibiting peptide (RIP) has been established as an effective inhibitor of staphylococcal infections. Non-peptide small molecule analogs based on a pharmacophore conforming to the putative atomic structure of RIP, can be identified by computer screening of that pharmacophore against established libraries of known small molecules other than peptides. One such identified structural analog is hamamelitannin. When tested for effective inhibition of staphylococcal infections, hamamelitannin demonstrated inhibition similar to that exhibited by RIP. Other analogs can be identified and similarly used.

Abstract: The invention features methods and compositions for treatment or prevention of infection by, or disease caused by infection with, certain species of bacteria, including in particular bacteria in which a RAP-type and/or TRAP-type molecule plays a role in pathogenesis. This includes Staphylococcus species.

Abstract: The present composition combines an RNAIII-inhibiting peptide (RIP) with an antimicrobial peptide, such as a cathelicidin, that is capable of binding and neutralizing lipidic and polyanionic components of bacterial cell envelope. In another embodiment, the RIP is combined with an antibiotic, with or without an antimicrobial peptide. The present composition is advantageously used in a method of treatment of bacterial sepsis.

Abstract: A biologically pure RNAIII inhibiting peptide (RIP), that includes five contiguous amino acids of the sequence YX2PX1TNF, where X1 is C, W, I or a modified amino acid, and X2 is K or S is provided. The RIP further includes amino acids having a sequence that differs from the sequence YX2PX1TNF by two substitutions or deletions, where X1 is C, W, I or a modified amino acid, and X2 is K or S. This agent offers improved protection against and treatment of staphylococcal infections, and related bacteria infections, in mammals.

Abstract: The invention features methods and compositions for treatment or prevention of infection by, or disease caused by infection with, Staphylococcus spp., particularly S. aureus. The treatment is effected by providing to the infection target a n amount of antibody, or antibody binding fragment, which binds specifically to RNAIII activating protein (RAP) which upregulates expression of virulence factors by a Staphylococcus infection in said host, or by raising a protective immune response in said host in the form of a circulating antibody titre through administration of RAP, or a fragment thereof, which promotes the expression of antibodies thereto by said host, which antibodies bind RAP and inhibit its ability to upregulate the virulence factors.

Abstract: A biologically pure RNAIII inhibiting peptide (RIP), that includes five contiguous amino acids of the sequence YX2PX1TNF, where X1 is C, W, I or a modified amino acid, and X2 is K or S is provided. The RIP further includes amino acids having a sequence that differs from the sequence YX2PX1TNF by two substitutions or deletions, where X1 is C, W, I or a modified amino acid, and X2 is K or S. The RIP does not consist of the sequence YSPX1TNF, where X1 is C, W, I or a modified amino acid. This agent offers improved protection against and treatment of staphylococcal infections, and related bacteria infections, in mammals.

Abstract: The bacterial protein OpuCA, an intracellular part of an ABC transporter, has been shown to interact directly with TRAP. The present invention provides methods and compositions directed at interfering with the interaction between OpuCA and TRAP. The resulting inhibition of TRAP advantageously will reduce pathogenesis of all bacteria that utilize this pathway. The present invention further provides methods and compositions directed at interfering with the interaction between TRAP and the extracellular substrate binding protein OpuCC, or the membrane-associated proteins OpuCB and OpuCD, which, like OpuCA, are encoded by the bacterial OpuC operon. Accordingly, the present methods and compositions will be useful in treating diseases caused by such bacteria.

Abstract: The invention features methods and compositions for treatment or prevention of infection by, or disease caused by infection with, certain species of bacteria, including in particular bacteria in which a RAP-type and/or TRAP-type molecule plays a role in pathogenesis. This includes Staphylococcus species.

Abstract: RNAIII inhibiting peptide (RIP) has been established as an effective inhibitor of staphylococcal infections. Non-peptide small molecule analogs based on a pharmacophore conforming to the putative atomic structure of RIP, can be identified by computer screening of that pharmacophore against established libraries of known small molecules other than peptides. One such identified structural analog is hamamelitannin. When tested for effective inhibition of staphylococcal infections, hamamelitannin demonstrated inhibition similar to that exhibited by RIP. Other analogs can be identified and similarly used.

Abstract: RNAIII-inhibiting peptide (RIP) advantageously treats or reduces the risk of biofilm formation on implanted bone cement, thus reducing the possibility of sustained chemotherapy, hospitalization, or surgical removal of the bone cement. Avoiding sustained chemotherapy reduces the risk of inducing antibiotic resistance. Accordingly, RIP can be used with antibiotics that otherwise would be reserved as a last resort, such as vancomycin. RIP potentiates the activity of vancomycin, minimizing the risk of inducing vancomycin-resistance. The present invention thus is expected to prolong significantly the effectiveness of antibiotics of last resort for the treatment of periprosthetic infection.

Abstract: Compositions comprising RIP are advantageously formulated in compositions allowing sustained release and protection from degradation, and improved therapeutic efficacy. To that end, RIP compositions may be delivered to the skin or mucosal membranes as a salve or the like. Alternatively or additionally, RIP compositions may be administered in polymeric nanoparticle carriers, which may be biodegradable. Such formulations are compatible with oral administration. The nanoparticle may accommodate a composition comprising a RIP and at least one other antimicrobial agent, e.g., an antibiotic or an antimicrobial peptide. The nanoparticle further may comprise a coating or moiety, such as an antibody or fragment thereof, to assist in cell targeting.

Abstract: The present composition combines an RNAIII-inhibiting peptide (RIP) with an antimicrobial peptide, such as a cathelicidin, that is capable of binding and neutralizing lipidic and polyanionic components of bacterial cell envelope. In another embodiment, the RIP is combined with an antibiotic, with or without an antimicrobial peptide. The present composition is advantageously used in a method of treatment of bacterial sepsis.

Abstract: RNAIII-inhibiting peptide (RIP) advantageously treats or reduces the risk of biofilm formation on implanted bone cement, thus reducing the possibility of sustained chemotherapy, hospitalization, or surgical removal of the bone cement. Unlike antibiotics, RIP eradicates biofilms without inducing resistant bacterial strains, making RIP particularly advantageous in this application. Biodegradable compositions comprising RIP also are provided.

Abstract: An apparatus and method for treating or preventing bacterial colonization of medical devices, or the host itself, comprise combining an RNAIII inhibiting peptide (RIP) with the medical device, optionally with an antibiotic. Further, RIP may be used in a lock technique, comprising adding sufficient solution comprising RIP to occupy a space within the device, which provides a high concentration of RIP at the actual or potential site of infection and prevents the space from filing with blood. The invention thus allows a clinician to maximize the amount of RIP and an antibiotic used to clean the medical device, while, at the same time, retaining the device within the host.

Abstract: The invention features methods and compositions for treatment or prevention of infection by, or disease caused by infection with, certain species of bacteria, including in particular bacteria in which a RAP-type and/or TRAP-type molecule plays a role in pathogenesis. This includes Staphylococcus species.

Abstract: Methods and compositions are provided for the treatment of staphylococcal infections.

Abstract: The invention features methods and compositions for treatment or prevention of infection by, or disease caused by infection with, certain species of bacteria, including in particular bacteria in which a RAP-type and/or TRAP-type molecule plays a role in pathogenesis. This includes Staphylococcus species.

Abstract: The invention features methods and compositions for treatment or prevention of infection by, or disease caused by infection with, Staphylococcus spp., particularly S. aureus.

Abstract: The present invention is directed to a protein isolated from S. aureus that is the target of RAP, called TRAP, which is characterized by a molecular weight of about 21 KDa, is capable of being phosphorylated by RAP, and comprises an amino acid sequence of SEQ ID NO:2. In addition, the present invention is directed towards an antibody immunoreactive with TRAP that is preferably a monoclonal antibody or a humanized antibody but may be a polyclonal antibody. The invention provides a method of treating S. aureus infection by administering such a TRAP-inhibiting agent. The invention also features methods for identifying compounds that inhibit TRAP activity and/or inhibit TRAP-RAP interaction.

Abstract: The invention features methods and compositions for treatment or prevention of infection by, or disease caused by infection with, Staphylococcus spp., particularly S. aureus.