History
Hydrogenosomes were isolated, purified, biochemically characterized and named in the early 1970s by D. G. Lindmark and M. Müller at Rockefeller University. In addition to this seminal study on hydrogenosomes, they also demonstrated, for the first time, the presence of pyruvate:ferredoxin oxido-reductase and hydrogenase in eukaryotes. Further studies were subsequentially conducted on the biochemical cytology and subcellular organization of anaerobic protozoan parasites (Trichomonas vaginalis, Tritrichomonas foetus, Monocercomonas sp., Giardia lamblia, Entamoeba sp., and Hexamita inflata). Using information obtained from hydrogenosomal and biochemical cytology studies these researchers determined the mode of action of metronidazole (Flagyl) in 1976. Metronidazole is today recognized as the gold standard chemotherapeutic agent for the treatment of anaerobic infections caused by prokaryotes (Clostridium, Bacteroides, Helicobacter) and eukaryotes (Trichomonas, Tritrichomonas, Giardia, Entamoeba). Metronidazole is taken up by diffusion. Once taken up by anaerobes, it is non-enzymatically reduced by reduced ferredoxin which is produced by the action of pyruvate:ferredoxin oxido-reductase. This reduction creates products toxic to the anaerobic cell, and allows for selective accumulation of the drug in anaerobes.
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