ANTICANDIDA ACTIVITY OF CISPENTACIN - THE ACTIVE-TRANSPORT BY AMINO-ACID PERMEASES AND POSSIBLE MECHANISMS OF ACTION

Cispentacin transport into Candida albicans CCH442 was via a specific inducible proline permease and other amino acid permeases. Drug entry was also dependent upon the proton motive force. The apparent K(m) and V(max) for drug uptake under induced conditions were 0.4 mM and 7 nmol/μl/min, respectively, with cellular accumulation in the mM range. Cispentacin uptake was competitively inhibited by L-proline with an apparent K(i) of 75 μM. Cispentacin did not charge to transfer-RNA or incorporate into protein; however, the compound did inhibit in vivo incorporation of [14C]lysine into protein and [3H]adenine into RNA as well as in vitro [14C]proline charging to transfer-RNA. Cispentacin did not inhibit amino acid biosynthesis in vivo but did elevate levels of several amino acids possibly by interfering with self- regulatory mechanisms. © 1993 Academic Press, Inc.