The history of Wolbachia and heartworm.

Wolbachia is the most widespread endosymbiont in animals, and its discovery in Dirofilaria immitis significantly advanced our understanding of heartworm disease (HWD). In 1995, Sironi and colleagues from the universities of Milan and Pavia, Italy, published a study titled "Molecular evidence for a close relative of the arthropod endosymbiont Wolbachia in a filarial worm" (Mol Biochem Parasitol. 74:223-7, 1995). In the 1970s, intracellular bacteria were observed in filarial nematodes by electron microscopy, but no one understood what they were or why they were there. There had been previous reports on the anti-filarial effects of tetracycline, but no connection with these bacteria had been made. Many years later, these bacteria were identified as belonging to the genus Wolbachia, marking a new chapter in filarial research. As soon as Wolbachia had been described in heartworms, there was a flurry of excitement in the scientific community. By 1999, Wolbachia had been described in a further nine species of animal and human filarial nematodes. Subsequent studies strongly suggested that Wolbachia are obligatory mutualist symbionts of D. immitis, and related research then focused on targeting Wolbachia in the treatment of HWD. Studies on the effects of doxycycline treatment in D. immitis-infected dogs reported that bacterial depletion in adult worms, elimination of microfilariae, and adult worm death were more effective when antibiotics were combined with macrocyclic lactones, and that use of this combination also avoided the deleterious post-adulticide effects of treatment with melarsomine. Dirofilaria immitis-infected dogs develop an immune response to Wolbachia, which likely contributes to the immunopathology of HWD. Insights into how D. immitis and Wolbachia interact were gained in 2012, when genome sequencing of these organisms was completed.