Fexinidazole and Corallopyronin A target -infected sheath cells present in filarial nematodes.

The discovery of the endosymbiotic bacteria as an obligate symbiont of filarial nematodes has led to antibiotic-based treatments for filarial diseases. While lab and clinical studies have yielded promising results, recent animal studies reveal that levels may rebound following treatment with suboptimal doses of the antibiotic rifampicin. Previous work showed that a likely source of the bacterial rebound in females were dense clusters of in ovarian tissue. The number, size, and density of these clusters were not diminished despite antibiotic treatment. Here we define the cellular characteristics of the clusters in (wBp) and identify drugs that also target them. We have evidence that the clusters originate from newly formed sheath cells adjacent to the ovarian Distal Tip Cells. The dramatically enlarged volume of an infected sheath cell is strikingly similar to endosymbiont-induced bacteriocytes found in many insect species. Ultrastructural analysis reveals that the clustered present within the sheath cells exhibit a distinct morphology and form direct connections with the oocyte membrane and possibly the cytoplasm. This includes membrane-based channels providing a connection between -infected sheath cells and oocytes. We also determined that the within the sheath cells are either quiescent or replicating at a very low rate. Screens of known antibiotics and other drugs revealed that two drugs, Fexinidazole and Corallopyronin A, significantly reduced the number of clustered located within the sheath cells.