Fermentation for Anticoccidial Agents

Coccidiosis is a parasitic disease of many animals caused by Coccidia, and it has become one of the most important parasitic diseases of poultry worldwide. According to statistics, the global poultry industry is estimated to lose more than $3 billion annually due to coccidiosis. Chemotherapy involving the use of anticoccidial reagents has played an important role in the development of the poultry industry in the last few years. Currently, the drugs that used to control this disease are polyether ionophore antibiotics derived from fermentation and synthetic compounds produced through chemical synthesis process. These anticoccidial reagents can be classified as synthetic drugs (chemicals) and polyether (fermentation products of Streptomyces and other fungi species). The polyether antibiotics or ionophores destroy coccidia by interfering with the balance of important ions such as sodium and potassium.

Fig 1. Anticoccidial drugs of the livestock industry. (Noack, S.; et al. 2019)

Fermentation Techniques Used for Anticoccidial Agents

Currently, fermentation technology has been applied to produce ionophores via using the Streptomyces and other fungi species. These ionophores have been validated to have broad-spectrum activity against most pathogens of coccidia and lack of development of drug resistance.

In general, anticoccidial active compounds can be isolated from the fermentation broth of the production strain by solvent extraction, silica gel column chromatography and preparative HPLC. Streptomyces spp. or Actinomyces spp are widely employed for the production of polyether antibiotics or ionophores:

Monovalent ionophores

• Monensin, produced by the fermentation of Streptomyces cinnamomi, has a broad-spectrum effect against Eimeria.
• Salinomycin can be isolated from Streptomyces albus.
• Narasin, a polyether antibiotic, obtained from Streptomyces aureofaciens

Monovalent glycosidic ionophores

• Maduramicin ionophore, isolated from the bacterium Actinomadura yumaensis, has a series of electronegative crown ethers capable of binding monovalent or divalent metal ions.
• Semduramicin, isolated from Actinomadura roserufa, is a highly effective drug against Eimeria.

Divalent ionophores

• Lasalocid, isolated from Streptomyces lasaliensis, has been shown to have anticoccidial activity in chickens.

Fig 2. Ionophores used as anticoccidials. (Noack, S.; et al. 2019)

Bacillus species-based fermentation products for the coccidiosis therapy

Bacillus spp. can synthesize antimicrobial cyclolipopeptides that can be produced by submerged and solid-state fermentation. In contrast to submerged fermentation, Bacillus species-based fermentation products (BSFP) produced by solid-state fermentation not only contain Bacillus spores but also have antimicrobial cyclic lipopeptides. The antimicrobial cyclic lipopeptides derived from Bacillus species have therapeutic effects on coccidiosis in animals.

Fermentation Method for Anticoccidial Agents

• Preparation of Inoculum

Vegetative cells grown on suitable medium are scraped from slants that have been inoculated with Streptomyces cultures. The resulting vegetative cells are then used to inoculate the inoculation jars.

• Fermentation Process

After a suitable growth period, the fermenters containing the same suitable growth medium are inoculated with fermented broth from the inocula.

• Recovery of the Product

Recovery of the crude or pure antibiotic compound after growth is complete.

• In Vitro Anticoccidial Testing

In vitro antimicrobial activity of the anticoccidial compounds is tested by standard methods.

Our Services

• Fermentation CDMO Service
• Strain Development Service
• Fermentation Process Optimization
• Fermentation for Special Small Molecules
• GRAS Services

BOC Sciences provides fermentation CDMO service for anticoccidial agents. With our complete quality management system and strong fermentation capabilities, we are able to help customers facilitate their fermentation related projects and support them from laboratory to commercialization.

Workflow of Our Service

Reference

1. Noack, S.; et al. Anticoccidial drugs of the livestock industry. Parasitology Research. 2019. 118(7): 2009-2026.