Fermentation for Antiprotozoal Agents

Antiprotozoal agent refers to any agent that kills or inhibits the growth of an organism known as a protozoan. Protozoa are similar to plants and animals in that they are eukaryotes with a well-defined nucleus. This distinguishes them from prokaryotes such as bacteria. Their metabolic processes are closer to those of their human hosts than those of prokaryotic bacterial pathogens. Therefore, many antibiotics that are effective in inhibiting bacteria are not active against protozoa. In addition, antiprotozoal agents sometimes can cause severe toxic effects in the host, especially on cells that exhibit high metabolic activity. Microorganisms and protozoa have become major causes of infectious disease, death and many global health problems since protozoa often cause a variety of diseases, including malaria and Chagas disease. Diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare.

The production of biologically active metabolites such as antiprotozoal compounds is an important step in the process of drug discovery and development based on natural products. In order to obtain potent compounds, they must be synthesized by biological fermentation process via using the corresponding producers, mainly microorganisms. In order to obtain efficient antiprotozoal compounds, the activity of crude extracts obtained by fermenting antagonistic bacteria in different media is optimized in terms of media and fermentation time to evaluate and determine which of them is the most suitable for producing antiprotozoal compounds.

Classification of protozoan parasites.Fig 1. Classification of protozoan parasites. (Seong-Min, L.; et al. 2019)

Hazards of Protozoal Infection

Protozoal diseases remain one of the major threats to animal health worldwide, especially in tropical and subtropical regions. Domestic and wild animals may also be reservoirs of such diseases, raising public health and safety concerns. In animal health, protozoal infection has caused significant economic losses to livestock and poultry worldwide.

  • Abortions in livestock
  • Widespread and rapidly spreading diarrheal diseases
  • Severe morbidity and mortality

Currently available antiprotozoal compounds.Fig 2. Currently available antiprotozoal compounds. (Seong-Min, L.; et al. 2019)

Production of Antiprotozoal Agents by Fermentation

A new microorganism has been isolated from soil samples and identified as Streptomyces lisandri. By submerged fermentation in a suitable medium, this streptomyces is able to produce three new related compounds, axenomycins A, B and D. In vitro test data indicates that these compounds are effective antiprotozoal agents with desired anthelmintic , antiprotozoal and antifungal activity.

Moreover, researchers have applied fermentation techniques to produce an antimicrobial peptide (AMPs): Leucinostatin A, which was isolated from a fungal fermentation broth. Leucinostatin A is also one of the most potent antiprotozoal compounds, inhibiting Plasmodium falciparum, Trypanosoma brucei, with reduced toxicity in vitro and in vivo.

A series of new antiprotozoal and antimicrobial compounds: 1,4-dihydroxy-5-phenyl-2-pyridinone alkaloids, 17-hydroxy-N-(O-methyl)septoriamycin A, 17-acetoxy-N-(O-methyl)septoriamycin A, 13-(S)-hydroxy-N-(O-methyl)septoriamycin A, and 13-(R)-hydroxy-N-(O-methyl)septoriamycin A were isolated from ethyl acetate extracts of the medium of the phytopathogen Septoria pistaciarum. Some of these fermentated compounds have showed significant activity against L. donovani promastigotes, and some of them showed moderate in vitro activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum.

Among the antiprotozoal reagents, in addition to some secondary metabolites produced by direct microbial fermentation, there are another type products that have undergone a series of modifications.

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BOC Sciences provides fermentation CDMO service for antiprotozoal 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.

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  1. Seong-Min, L.; et al. Recent Advances in the Discovery of Novel Antiprotozoal Agent. Molecules. 2019. 24(21): 3886.

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