Tetracycline inhibits development of the infective-stage larvae of filarial nematodes in vitro

In recent years, studies have linked tetracycline treatment of filaria-infe cted animals with reduced adult worm burdens and decreased levels of microf ilaremia. These observations are believed to be attributable to clearance o f Wolbachia, intracellular rickettsial-like organisms found within filarial tissues. Although maximal worm reductions were observed when treatment was initiated early in infection, it is not known whether tetracycline inhibit s development of infective-stage larvae. To address this issue, we studied the effect of tetracycline on three different species of filarial nematodes , Brugia malayi, Brugia pahangi, and Dirofilaria immitis, in a serum-free i n vitro system supporting molting to the fourth larval stage. Tetracycline was capable of inhibiting L3 to L4 molting within a dosage range similar to that reported for susceptible rickettsial organisms. However, Wolbachia DN A could still be detected in nematodes from tetracycline-treated cultures. In addition, three other antibiotics with anti-rickettsial and anti-chlamyd ial activity (chloramphenicol, erythromycin, and ciprofloxacin) failed to i nhibit L3 to L4 molting. Although tetracycline is capable of completely blo cking molting of infective-stage larvae, it remains possible that this effe ct is due to pharmacological activities unrelated to its anti-rickettsial f unctions. (C) 2000 Academic Press.