Methods and compositions for treating a microbial infection

Abstract

Described herein are methods and compositions for treating and/or preventing a microbial infection. Aspects of the invention relate to administering to a subject an agent that inhibits CGRP release and CGRP receptors. In some embodiments of any of the aspects, a subject has been diagnosed with having, or is at risk of having, a microbial infection.

1 . A method for treating or preventing a microbial infection in a subject, the method comprising; administering to a subject in need thereof an agent that inhibits Calcitonin gene-related peptide (CGRP) activity, CGRP release, and/or CGRP receptor signaling in an amount and for a duration sufficient to treat or prevent a microbial infection. 
     
     
         2 .- 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the agent is an inhibitor of Transient Receptor Potential Vanilloid 1 (TRPV1)-expressing neurons. 
     
     
         6 . The method of  claim 5 , wherein the inhibitor of TRPV1-expressing neurons is Resiniferatoxin (RTX). 
     
     
         7 . The method of  claim 1 , wherein the agent is selected from the group consisting of: a competitive inhibitor of CGRP; an antagonist of CGRP receptors and their signaling; an anti-CGRP antibody or antibody reagent; a small molecule that inhibits CGRP; a nucleic acid that encodes an inhibitor of CGRP; a polypeptide that inhibits CGRP; a siRNA that inhibits CGRP activity, release, or receptor signaling; a shRNA that inhibits CGRP activity, release, or receptor signaling; and a miRNA that inhibits CGRP activity, release, or receptor signaling. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 7 , wherein the anti-CGRP antibody is ALD403, LY2951742, AMG 334, or TEV-48125. 
     
     
         11 .- 16 . (canceled) 
     
     
         17 . The method of  claim 7 , wherein the small molecule is selected from the group consisting of: olcegepant, obrogepant, tacagepant, Avitriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, galcanezumab, eptinezumab, erenumab, fremanezumab, (piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide (BMS 694153), atogepant, and MK-3207. 
     
     
         18 . The method of  claim 1 , wherein the agent inhibits a CGRP receptor. 
     
     
         19 . The method of  claim 18 , wherein the CGRP receptor is RAMP1/CALCRL. 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 7 , wherein the polypeptide comprises CGRP 8-37  peptide. 
     
     
         23 .- 25 . (canceled) 
     
     
         26 . The method of  claim 1 , wherein the microbial infection comprises a bacterium which is resistant to at least one antibiotic. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein the microbial infection comprises a gram-positive bacterial infection. 
     
     
         29 .- 36 . (canceled) 
     
     
         37 . The method of  claim 1 , wherein the microbial infection is selected from the group consisting of: a  Streptococcus  infection, a  Staphylococcus  infection, a  Corynebacterium  infection, a  Listeria  infection, a  Clostridium  infection, a  Pseudomonas aeruginosa  infection, an  Escherichia coli  infection, a  Klebsiella  infection, an  Aeromonas  infection, and a  Neisseria  infection. 
     
     
         38 . The method of  claim 1 , wherein the microbial infection is a skin, soft tissue, respiratory tract or lung, or subcutaneous infection. 
     
     
         39 .- 41 . (canceled) 
     
     
         42 . The method of  claim 1 , wherein the microbial infection is a systemic infection. 
     
     
         43 .- 48 . (canceled) 
     
     
         49 . The method of  claim 1 , wherein the microbial infection comprises a fungal infection, a burn, or a burn comprising a microbial infection. 
     
     
         50 .- 52 . (canceled) 
     
     
         53 . The method of  claim 1 , further comprising administering to a subject a second therapeutic agent. 
     
     
         54 . The method of  claim 53 , wherein the second therapeutic agent is an antibiotic, antifungal, or antimicrobial agent. 
     
     
         55 .- 70 . (canceled) 
     
     
         71 . A composition for treating or preventing a microbial infection in a subject, the composition comprising; an amount of an agent that inhibits Calcitonin gene-related peptide (CGRP) activity, CGRP release, and/or CGRP receptor signaling sufficient to treat or prevent a microbial infection. 
     
     
         72 . (canceled) 
     
     
         73 . (canceled) 
     
     
         74 . The composition of  claim 71 , further comprising a second therapeutic agent. 
     
     
         75 .- 80 . (canceled) 
     
     
         81 . A method for treating or preventing a microbial infection in a subject, the method comprising;
 a. receiving the results of an assay that diagnoses a subject as having or at risk of having a microbial infection;   b. administering to a subject in need thereof an agent that inhibits Calcitonin gene-related peptide (CGRP) activity, CGRP release, and/or CGRP receptor signaling in an amount and for a duration sufficient to treat or prevent a microbial infection.