THE EFFECT OF SULINDAC ON ARYLAMINE N-ACETYLTRANSFERASE ACTIVITY IN PSEUDOMONAS-AERUGINOSA

Arylamine N-acetyltransferase (NAT) activity in Pseudomonas aeruginosa was inhibited by sulindac, a drug proposed for cancer prevention. By using high performance liquid chromatography, the NAT activity for ace tylation of 2-aminofluorene (2-AF) was examined. The cytosolic NAT act ivity in P. aeruginosa ATCC 27853 was 5.32 +/- 0.36 nmol/min/mg of pro tein. Sulindac displayed a dose-dependent inhibition to cytosolic NAT activity in P. aeruginosa with an IC50 value of about 0.46 mM. The NAI activity measured from intact P. aeruginosa cells was 1.39 +/- 0.12 n mol/min/10(10) CFU and this activity was inhibited by sulindac in a si milar dose-dependent fashion with an IC50 value of similar to 0.42 mM. Time-course experiments showed that NAT activity measured from intact Fl aeruginosa cells was inhibited by sulindac for at least 3 h. Using standard steady-state kinetic analysis, it was demonstrated that suli ndac was a possible noncompetitive inhibitor to NAT activity in Fl aer uginosa. The results suggest that sulindac suppressed the NAT activity in Fl aeruginosa.