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AssigneeThe Rockefeller University
InventorsRobert C. Nowinski, Vincent A. Fischetti, Assaf Raz
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The present invention relates to methods and compositions for use in modulating, including inhibiting the growth and/or reducing the virulence of, gram-positive bacteria. The present invention provides methods and compositions for disrupting the cell wall and/or cell membrane in gram-positive bacteria such that cell wall or cell membrane target(s) are rendered exposed or accessible and sensitive to a modulation thereof. Methods for modulation of one or more gram-positive bacterial cell wall or cell membrane targets in a gram-positive bacteria are provided comprising disrupting the cell wall such that the cell wall or cell membrane target, which is particularly a sortase, is rendered exposed or accessible and sensitive to a modifying, modulating or binding agent, which is particularly an antibody or fragment thereof, wherein the cell wall or cell membrane target is inaccessible or relatively insensitive to the modifying, modulating or binding agent in the absence of cell wall disruption.
A method of reducing virulence of a gram positive bacteria in a mammal comprising administering to said mammal one or more cell wall disrupting agent(s) and one or more cell wall or cell membrane target inhibiting agent(s), wherein the inhibiting agent reduces virulence of the bacteria to a significantly greater extent in the presence of the cell wall disrupting agent than in its absence, wherein the one or more cell wall disrupting agent(s) is selected from the group of antibiotics, anti-microbial peptides, polycationic peptides, cell wall degrading enzymes, and catalytic antibodies having inherent antibacterial activity, and wherein the one or more cell wall disrupting agent(s) is effective in the method at a concentration which is less than the minimally inhibitory concentration (MIC) of said one or more cell wall disrupting agent(s).
A method of treatment or amelioration of a gram-positive bacterial infection in a mammal wherein the bacteria are Staphylococcus or Streptococcus bacteria comprising administering to said mammal one or more cell wall disrupting agent(s) and one or more cell wall or cell membrane target inhibiting agent(s), wherein the inhibiting agent inhibits or ameliorates the bacterial infection to a significantly greater extent in the presence of the cell wall disrupting agent than in its absence, wherein the one or more cell wall disrupting agent(s) is selected from the group of antibiotics, anti-microbial peptides, polycationic peptides, and cell wall degrading enzymes having inherent antibacterial activity, and wherein the one or more cell wall disrupting agent(s) is effective in the method at a concentration which is less than the minimally inhibitory concentration (MIC) of said one or more cell wall disrupting agent(s).
A method of inhibiting or preventing growth of Staphylococcus or Streptococcus bacteria by contacting said bacteria with one or more cell wall and/or cell membrane disrupter and one or more cell wall and/or cell membrane target inhibiting agent, wherein the one or more cell wall and/or cell membrane disrupter is selected from the group of antibiotics, anti-microbial peptides, polycationic peptides, and cell wall degrading enzymes having inherent antibacterial activity, and wherein the one or more cell wall disrupting agent(s) is effective in the method at a concentration which is less than the minimally inhibitory concentration (MIC) of said one or more cell wall disrupting agent(s).
Dependencies are inferred from the claim text.