Avermectins, New Family of Potent Anthelmintic Agents: Producing Organism and Fermentation

Abstract

The avermectins are a complex of chemically related agents which exhibit extraordinarily potent anthelmintic activity. They are produced by a novel species of actinomycete, NRRL 8165, which we have named Streptomyces avermitilis . The morphological and cultural characteristics which differentiate the producing organism from other species are described. The avermectins have been identified as a series of macrocyclic lactone derivatives which, in contrast to the macrolide or polyene antibiotics, lack significant antibacterial or antifungal activity. The avermectin complex is fully active against the gastrointestinal nematode Nematospiroides dubius when fed to infected mice for 6 days at 0.0002% of the diet. Fermentation development, including medium modification and strain selection, resulted in increasing the broth yields from 9 to 500 μg/ml.

Effect of ivermectin on the life cycle and larval fat body of Culex quinquefasciatus

“…Ivermectin is a group of macrocyclical lactones, derived from 22,23-dihydro avermectin B1, with low water solubility that is produced by Streptomyces avermectilis (Burg, et al, 1979;Egerton et al, 1979;Miller et al, 1979;Chabala et al, 1980), being largely used as anti-parasitic in the domestic animals (Aziz et al, 1982;Campbell et al, 1983). Previous studies have shown that the avermectins are lethal for immature and adult stages of some insect orders (Strong and Brown, 1987) and efficient for the control of Culex quinquefasciatus (Freitas et al, 1996).…”

The autoregulator receptor homologue AvaR3 plays a regulatory role in antibiotic production, mycelial aggregation and colony development of Streptomyces avermitilis

“…Streptomyces avermitilis produces a family of polyketide macrocyclic lactones known as avermectins, which have potent antiparasitic and broad-spectrum activities against nematodes and arthropod parasites (Burg et al, 1979), together with two other families of polyketide antibiotics, filipins and oligomycins. The biosynthetic pathways of the three types of antibiotic have been predicted and partially elucidated (Ikeda et al, 1999;Omura et al, 2001), while genetic information on the regulatory mechanism of antibiotic production has so far been limited.…”

Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations

“…The avermectin family displayed extraordinarily potent anthelmintic properties. [15][16][17] Ivermectin is a safer, more potent semisynthetic mixture of two chemically modified avermectins, comprising 80% of 22,23-dihydroavermectinB1a and 20% 22,23-dihydroavermectin-B1b (Figure 3). …”