Pyrazinamide (PZA) is a drug listed on the World Health Organization’s list of essential medicines due to its crucial role in treating tuberculosis. PZA is known to enter the cell and be hydrolyzed into pyrazonoic acid (POA). Once hydrolyzed, it has been shown to do two things: collapse the membrane potential, and inhibit ribosomal rescue. We are interested in the membrane interaction due to this collapsing of the membrane potential. To look at this, NMR studies of reverse micelle microemulsions were used to identify the location of PZA/POA in a model of a membrane leaflet. Interactions between POA/PZA and Langmuir monolayers, prepared from various phospholipids, were also measured using a Langmuir trough. These studies help characterize the drug-membrane interaction, which provides insight into PZA’s mechanism of disrupting membrane potential.

Exploring the interactions between the anti-tuberculosis agent, pyrazinamide/pyrazonoic acid, and lipid model membrane systems

253rd National Meeting (2017)

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