Bicarbonate as a potentiator for antimicrobial agents
Provided herein are methods and compositions for modulating a microorganism's response to an antimicrobial agent. In one embodiment, the method comprises contacting the microorganism with an antimicrobial agent and bicarbonate. In one embodiment, provided herein are methods for treating a microbial infection comprising administering to a subject in need an effective amount of (i) bicarbonate and (ii) an antimicrobial agent. Also provided herein are methods of screening for antimicrobial compounds.
1 . A method for inhibiting the growth of a bacterium, comprising contacting the bacterium with an effective amount of (i) bicarbonate and (ii) an antimicrobial agent, wherein the antimicrobial agent is azithromycin, and the effective amount of the bicarbonate is a concentration of greater than 150 mM.
2 . The method of claim 1 , wherein the effective amount of the bicarbonate is greater than 175 mM.
3 . The method of claim 1 , wherein the effective amount of the bicarbonate is 175 mM to 200 mM.
4 . The method of claim 1 , wherein the bicarbonate is sodium bicarbonate, ammonium bicarbonate, lithium bicarbonate, potassium bicarbonate, magnesium bicarbonate, calcium bicarbonate or zinc bicarbonate.
5 . The method of claim 1 , wherein the bicarbonate is present in a first composition and the antimicrobial agent is present in a second composition.
6 . The method of claim 1 , wherein the bacterium is a Gram negative bacterium.
7 . The method of claim 1 , wherein the bacterium is a Gram positive bacterium.
8 . The method of claim 1 , wherein the bacterium is a species of Acetobacter, Acinetobacter, Actinomyces, Aerococcus, Agrobacterium, Anaplasma, Azorhizobium, Azotobacter, Bacillus, Bacteroides, Bartonella, Bordetella, Borrelia, Brucella, Burkholderia, Calymmatobacterium, Campylobacter, Chlamydia, Chlamydophila, Clostridium, Corynebacterium, Coxiella, Ehrlichia, Enterobacter, Enterococcus, Escherichia, Francisella, Fusobacterium, Gardnerella, Haemophilus, Helicobacter, Klebsiella, Lactobacillus, Lactococcus, Legionella, Listeria, Methanobacterium, Microbacterium, Micrococcus, Moraxella, Mycobacterium, Mycoplasma, Neisseria, Pasteurella, Pediococcus, Peptostreptococcus, Porphyromonas, Prevotella, Pseudomonas, Rhizobium, Rickettsia, Rochalimaea, Rothia, Salmonella, Serratia, Shigella, Sarcina, Spirillum, Spirochaetes, Staphylococcus, Stenotrophomonas, Streptobacillus, Streptococcus, Tetragenococcus, Treponema, Vibrio, Viridans, Wolbachia or Yersinia.
9 . The method of claim 1 , wherein the bacterium is Pseudomonas aeruginosa.
10 . The method of claim 1 , wherein the bacterium is Staphylococcus aureus.
11 . The method of claim 1 , wherein the bicarbonate is administered topically, and the antimicrobial agent is administered orally.
12 . The method of claim 11 , wherein the bicarbonate is administered intranasally.
13 . The method of claim 11 , wherein the bicarbonate is administered as an aerosol or nebulized spray.
14 . A kit comprising i) a first bicarbonate composition and ii) a second antimicrobial composition, wherein the first composition comprises bicarbonate in an amount of greater than 150 mM and a pharmaceutically acceptable carrier, and the second composition comprises an antimicrobial agent azithromycin.
15 . The kit of claim 14 , wherein the first composition is prepared for administration topically, and the second composition is prepared for oral administration.
16 . The kit of claim 14 , wherein the first composition is an aerosol or nebulized spray.
17 . The kit of claim 14 , wherein the amount of the bicarbonate is greater than 175 mM.
18 . The kit of claim 14 , wherein the amount of the bicarbonate is an amount of 175 mM to 200 mM.