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Ivermectin Inhibits Growth of Chlamydia trachomatis in Epithelial Cells





Avermectins are macrocyclic lactone derivatives which are produced during fermentation of Streptomyces avermectinius, a species of actinomycete isolated from soil samples in Japan. Eight avermectins are produced by S. avermectinius (A1a, A1b, A2a, A2b, B1a, B1b, B2a, and B2b). The A series molecules contain a 5′-methoxyl group, while the B series contain a 5′-hydroxyl group and have more potent anti-parasitic activity [1], [2], [3]. Improved efficacy as a broad-spectrum anti-parasitic was achieved for the B1 compounds by selective hydrogenation utilizing Wilkinson’s catalyst (RhCl(PPh3)3), with the resultant product (22,23-dihydroavermectin B1) being given the name ivermectin [4]. Following considerable success as an anti-helminthic agent in veterinary practice, including use for treatment of Onchocerca cervicalis in horses, ivermectin entered clinical trials for use in humans against Onchocerca volvulus, a nematode which causes onchocerciasis (“river blindness”) [5]. Efficacious use in humans has extended to lymphatic filariasis [6], head-lice infestation [7], and scabies [8]. However, avermectins have not been previously described to have anti-bacterial activity [5].

Here we demonstrate that ivermectin inhibits growth of Chlamydia trachomatis during infection of human cervical epithelial cells, suggesting that avermectins may have previously undescribed anti-bacterial activity against pathogenic obligate intracellular bacteria, potentially via indirect effects on the host-cell.


Chlamydiae are obligate intracellular bacteria which mature through a unique biphasic developmental cycle, infecting as metabolically inert elementary bodies (EBs) and maturing into metabolically active but non-infectious reticulate bodies (RBs), which proliferate before condensing into infectious EBs to complete the cycle [9], [10], [11]. C. trachomatis strains, which are the leading cause of bacterial sexually transmitted disease and first cause of preventable blindness [12], primarily infect mucosal epithelial cells.


Open Access. Read more at:

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0048456





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