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AssigneesThe Rockefeller University, Contrafect Corporation
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 for modulation of one or more gram-positive bacterial cell wall or cell membrane targets in a gram-positive bacteria comprising disrupting the cell wall such that the cell wall or cell membrane target is rendered exposed or accessible and sensitive to a modifying, modulating or binding agent, wherein the cell wall or cell membrane target is inaccessible, relatively insensitive, or less sensitive to the modifying, modulating or binding agent in the absence of cell wall disruption.
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A method of treatment or amelioration of a gram-positive bacterial infection 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 modifying or modulating agent(s), wherein the modifying or modulating agent does not inhibit the bacterial infection in the absence of the cell wall disrupting agent or inhibits or ameliorates the bacterial infection to a significantly greater extent in the presence of the cell wall disrupting agent than in its absence.
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An assay system for isolating test agents or compounds capable of rendering a gram-positive bacterial cell wall and/or cell membrane target in a bacterial cell sensitive to a target modifying, modulating or binding agent comprising contacting the bacterial cell with a test agent or compound in the presence of a target modifying, modulating or binding agent and assessing the activity of the target or binding of the binding agent to the target, wherein the binding of the binding agent to the target is increased and/or the activity of the target is modified or modulated or is modified or modulated more significantly in the presence of the test agent when compared to the absence of test agent.
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A method of inhibiting or preventing growth of a gram positive bacteria by contacting said bacteria with one or more cell wall and/or cell membrane disrupter and one or more target modifying, modulating or binding agent.
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A composition comprising one or more gram-positive bacteria cell wall or cell membrane disrupter and one or more gram-positive cell wall or cell membrane target modifying, modulating or binding agent wherein the composition is capable of disrupting the cell wall such that the cell wall or cell membrane target is rendered exposed or accessible and sensitive to a modifying, modulating or binding agent, wherein the cell wall or cell membrane target is inaccessible, relatively insensitive, or less sensitive to the modifying, modulating or binding agent in the absence of the cell wall disrupting agent.
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Dependencies are inferred from the claim text.