Abstract
Antibiotic treatment has emerged as a promising strategy to sterilize and kill filarial nematodes due to their dependence on their endosymbiotic bacteria, Wolbachia. Several studies have shown that novel and FDA-approved antibiotics are efficacious at depleting the filarial nematodes of their endosymbiont, thus reducing female fecundity. However, it remains unclear if antibiotics can permanently deplete Wolbachia and cause sterility for the lifespan of the adult worms. Concerns about resistance arising from mass drug administration necessitate a careful exploration of potential Wolbachia recrudescence. In the present study, we investigated the long-term effects of the FDA-approved antibiotic, rifampicin, in the Brugia pahangi jird model of infection. Initially, rifampicin treatment depleted Wolbachia in adult worms and simultaneously impaired female worm fecundity. However, during an 8-month washout period, Wolbachia titers rebounded and embryogenesis returned to normal. Genome sequence analyses of Wolbachia revealed that despite the population bottleneck and recovery, no genetic changes occurred that could account for the rebound. Clusters of densely packed Wolbachia within the worm’s ovarian tissues were observed by confocal microscopy and remained in worms treated with rifampicin, suggesting that they may serve as privileged sites that allow Wolbachia to persist in worms while treated with antibiotic. To our knowledge, these clusters have not been previously described and may be the source of the Wolbachia rebound.
Highlights
Onchocerciasis, commonly known as river blindness, and lymphatic filariasis (LF), commonly known as elephantiasis, are neglected tropical diseases caused by filarial worms that together affect an estimated 86 million people worldwide [1]
We investigated the use of jirds infected with Brugia pahangi to assess the effects of rifampicin on Wolbachia and worm survival in an 8-month time course study in which Wolbachia titers were determined using adult worms recovered from animals treated with a oneweek dosing regimen of rifampicin
We hypothesized that rifampicin would deplete worms of Wolbachia which would eventually lead to adult worm death in jirds infected with Brugia pahangi
Summary
Onchocerciasis, commonly known as river blindness, and lymphatic filariasis (LF), commonly known as elephantiasis, are neglected tropical diseases caused by filarial worms that together affect an estimated 86 million people worldwide [1]. River blindness is caused by the release of thousands of microfilariae (mf) from adult Onchocerca volvulus females residing in subcutaneous tissues. While many infections are asymptomatic, individuals that develop the disfiguring disease often experience pain and severe lymphedema typically in the arms, legs, breasts and genitalia [2]. This can result in stigma associated with elephantiasis and extreme economic loss for individuals suffering from this disease [3]. The years lived with disability (YLDs) for LF and onchocerciasis are estimated to be 1.4 million and 1.3 million, respectively [1]
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