Tetracycline therapy targets intracellular bacteria in the filarial nematode Litomosoides sigmodontis and results in filarial infertility

Intracellular bacteria have been described in several species of filarial n ematodes, but their relationships with, and effects on, their nematode host s have not previously been elucidated. In this study, intracellular bacteri a were observed in tissues of the rodent parasite Litomosoides sigmodontis by transmission electron microscopy and by immunohistochemistry using antie ndobacterial heat shock protein-60 antisera Molecular phylogenetic analysis of the bacterial 16S ribosomal RNA gene, isolated by PCR, showed a close r elationship to the rickettsial Wolbachia endobacteria of arthropods and to other filarial intracellular bacteria. The impact of tetracycline therapy o f infected rodents on L. sigmodontis development was analyzed in order to u nderstand the role(s) these bacteria might play in filarial biology Tetracy cline therapy, when initiated with L. sigmodontis infection, eliminated the bacteria and resulted in filarial growth retardation and infertility. If i nitiated after microfilarial development, treatment reduced filarial fertil ity. Treatment with antibiotics not affecting rickettsial bacteria did not inhibit filarial development. Acanthocheilonema viteae filariae were shown to lack intracellular bacteria and to be insensitive to tetracycline. These results suggest a mutualistic interaction between the intracellular bacter ia and the filarial nematode. Investigation of such a mutualism in endobact eria-containing human filariae is warranted for a potential chemotherapeuti c exploitation.