Effects of metronidazole and tinidazole on NTPDase1 and ecto-5′-nucleotidase from intact cells ofTrichomonas vaginalis

Abstract

Here we report the effects of metronidazole and tinidazole on NTPDase1 and ecto-5P-nucleotidase from intact cells of Trichomonas vaginalis. Adenosine triphosphate (ATP) and adenosine diphosphate (ADP) hydrolysis was 5-to 7-fold higher for the fresh clinical strain, when compared with the ATCC (American Type Culture Collection) strain. ATP hydrolysis was activated in the presence of metronidazole in the ATCC strain, whilst it was inhibited 33% by 50 WM tinidazole in a fresh clinical isolate. The treatment of cells in the presence of metronidazole for 2 h inhibited ATP and ADP hydrolysis, whilst treatment with tinidazole inhibited ATP and ADP hydrolysis only in the fresh clinical isolate. The drugs did not change the ecto-5P-nucleotidase activity for both strains. Our results suggest that the modulation of extracellular ATP and ADP levels during treatment with these drugs could be a parasitic defence strategy as a survival mechanism in an adverse environment.

The Synergistic Effect of Mud Crab Antimicrobial Peptides Sphistin and Sph12−38 With Antibiotics Azithromycin and Rifampicin Enhances Bactericidal Activity Against Pseudomonas Aeruginosa

“…However, the other six antibiotics had no significant synergistic effect against P. aeruginosa when each of them was combined with the AMPs. Among the six antibiotics, as previously reported (Menninger and Otto, 1982;Nord and Kager, 1983;Gardner and Hill, 2001;Raether and Hanel, 2003;Tasca et al, 2003), tinidazole and clindamycin also have intracellular targets. Among the remaining four antibiotics, the three antibiotics including penicillin, ceftizoxime, and cefotiam are all β-lactam antibiotics, while vancomycin is a glycopeptide antibiotic (Kahne et al, 2005).…”

“…With the decrease of intracellular concentration of tinidazole due to the reduction reaction, more tinidazole could enter the cells, thereby maintaining the inhibition activity of anaerobic bacteria. In aerobic bacteria and mammalian cells, they have relatively high redox potentials and are also rich in oxygen molecules than anaerobic organisms or protozoa, which will hinder the reduction reaction (Nord and Kager, 1983;Tasca et al, 2003). Because P. aeruginosa is an aerobic bacterium, we speculated that tinidazole will not have much effect on P. aeruginosa due to the lack of anaerobic condition in cells.…”

“…When tinidazole diffused into bacterial cells, the nitro group of tinidazole will be reduced to shortlived and toxic free radicals. The toxic intermediates covalently bind to DNA, causing DNA damage and ultimately cell death (Nord and Kager, 1983;Gardner and Hill, 2001;Raether and Hanel, 2003;Tasca et al, 2003). With the decrease of intracellular concentration of tinidazole due to the reduction reaction, more tinidazole could enter the cells, thereby maintaining the inhibition activity of anaerobic bacteria.…”

A systematic review of the literature on mechanisms of 5-nitroimidazole resistance inTrichomonas vaginalis

“…Thus, modulation of extracellular ATP and ADP levels may be a defense strategy of T. vaginalis in response to unfavourable environmental conditions (i.e. drug pressure) (Tasca et al ., 2003).…”

Trichomonas vaginalis: cytochemical localization of a NTPDase1 and an ecto-5′-nucleotidase and effects of adenine nucleotides on cellular viability

“…Protein was measured by the Coomassie blue method (Bradford 1976). The NTPDase1 and ecto-5¢-nucleotidase activities were measured as previously described (Tasca et al 2003b). All samples were run in triplicate, with similar results achieved in at least four different cell suspensions.…”