The endosymbiont Wolbachia rebounds following antibiotic treatment

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 endosy...

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Bibliographic Details
Published in:PLoS pathogens 2020-07, Vol.16 (7), p.e1008623
Main Authors: Gunderson, Emma L, Vogel, Ian, Chappell, Laura, Bulman, Christina A, Lim, K C, Luo, Mona, Whitman, Jeffrey D, Franklin, Chris, Choi, Young-Jun, Lefoulon, Emilie, Clark, Travis, Beerntsen, Brenda, Slatko, Barton, Mitreva, Makedonka, Sullivan, William, Sakanari, Judy A
Format: Article
Language:English
Subjects:
Animals
Antibiotics
Biology and Life Sciences
Brugia pahangi - microbiology
Clusters
Confocal microscopy
Control
Depletion
Developmental biology
Drug dosages
Embryogenesis
Embryonic growth stage
Fecundity
Female
Females
Filariasis - microbiology
Filaricides - pharmacology
Funding
Genomes
Gerbillinae
Infectious diseases
Investigations
Life span
Long-term effects
Medical research
Medicine and Health Sciences
Nematodes
Nucleotide sequence
Parasitology
Patient outcomes
Pharmaceuticals
Population bottleneck
Recurrence (Disease)
Rifampin
Rifampin - pharmacology
Sterility
Supervision
Tropical diseases
Wolbachia
Wolbachia - drug effects
Worms
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1008623