Method for Treating and/or Preventing Bacteriophage Lysis During Fermentation
The subject invention relates to enhancing for the production of microorganisms and/or their growth by-products by treating and/or preventing bacteriophage contamination of bacterial cultures. Advantageously, the methods can help reduce the likelihood of total and/or partial culture loss through the direct control of bacteriophages and/or prophages that may be present in the culture. In certain embodiments, the method comprise applying an antiviral composition comprising, for example, ribavirin, to the nutrient medium in which a microorganism is being cultivated.
1 . A method of cultivating a bacterial strain and/or producing a growth by-product of a bacterial strain, the method comprising:
a) inoculating a nutrient medium with the strain;
b) applying an antiviral composition to the nutrient medium; and
c) cultivating the strain to produce a culture having a desired cell density and/or a desired concentration of the growth by-product,
wherein the antiviral composition comprises one or more antiviral compounds that interfere with viral DNA or RNA synthesis and/or interfere with viral DNA or RNA polymerase activity, and
wherein the antiviral composition controls a bacteriophage in the culture but does not harm the bacterial strain.
2 . The method of claim 1 , wherein the antiviral composition comprises ribavirin.
3 . The method of claim 1 , wherein the bacteria is a strain of Bacillus, Azotobacter, Pseudomonas or Rhodococcus.
4 . The method of claim 1 , wherein the nutrient medium is solid or liquid.
5 . The method of claim 1 , wherein the nutrient medium comprises sources of nitrogen and carbon.
6 . The method of claim 1 , wherein about 0.5 g/L to about 10.0 g/L of the antiviral composition is applied to the nutrient medium.
7 . The method of claim 1 , wherein the antiviral composition is applied prior to, or concurrently with, inoculating the nutrient medium.
8 . The method of claim 1 , wherein the antiviral composition is applied after inoculating the nutrient medium.
9 . The method of claim 1 , further comprising testing the culture for the presence of a bacteriophage infection.
10 . The method of claim 9 , wherein, if a bacteriophage infection is detected, the method further comprises applying one or more additional applications of the antiviral composition.
11 . The method of claim 1 , wherein the antiviral composition comprises one or more of ribavirin, valacyclovir, acyclovir, famciclovir, ganciclovir, valganciclovir, brivudin, cidofovir, fomivirsen, foscarnet, penciclovir, vidarabine, favipiravir, galidesivir, remdesivir, mericitabine, moroxydine, triazavirin, asunaprevir, boceprevir, ciluprevir, danoprevir, faldaprevir, glecaprevir, grazoprevir, narlaprevir, paritaprevir, simeprevir, sovaprevir, telaprevir, vaniprevir, vedroprevir, voxilaprevir, daclataasvir, elbasvir, ledipasvir, odalasvir, ombitasvir, pibrentasvir, ravidasvir, ruzasvir, samatasvir, velpatasvir, beclabuvir, dasabuvir, deleobuvir, filibuvir, setrobuvir, sofosbuvir, radalbuvir, uprifosbuvir, pleconaril, umifenovir, adapromione, amantadine, rimantadine, oseltamivir, zanamivir, peramivir, and laninamivir.
12 . The method of claim 1 , wherein the bacteriophage is from Cystoviridae or Leviviridae.