Effects of a derivative of serotonin (deoxyfructoserotonin) and other antileprosy drugs on attachment and uptake of Mycobacterium leprae by Schwann cells in vitro.

The association (attachment and/or uptake) of Mycobacterium leprae with cultured Schwann cells was studied at 8 and 72 h in the presence of a new antileprosy compound, deoxyfructoserotonin (DFS), as well as conventional antileprosy drugs such as rifampin (RFP) and 4,4'-diaminodiphenyl sulfone (DDS). DFS significantly inhibited bacterial association with Schwann cells at 8 h. RFP also affected the association of M. leprae but not to the same extent as DFS. A similar inhibition at 8 h was noted when M. leprae but not Schwann cells were pretreated with DFS or RFP for 5 days before infection of cultures, implying that modulation was achieved through some form of drug action on bacteria. DDS had no effect on M. leprae association; however, the combination of DFS and DDS was neither antagonistic nor additive. At 72 h postinfection, when attached but noninternalized bacteria were removed with trypsin-EDTA from Schwann cell cultures containing DFS or RFP, a 50% reduction in the number of bacteria in the drug-treated group was obtained as compared with the numbers in drug-free cultures. This indicated a slow entry of M. leprae into Schwann cells in the presence of these drugs. Collectively, these observations point to differing requirements for late and early association of M. leprae with Schwann cells, besides suggesting a role for DFS and RFP in the prevention and minimization of M. leprae-induced nerve damage in vivo.