Inhibitory targets of fluoroquinolone antibiotics in the photosynthetic electron transport chain: SAR modeling analysis and in vitro binding studies

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Ludmilla Aristilde, ludmilla@nature.berkeley.edu, Molecular Toxicology Group, University of California at Berkeley, 117 Morgan Hall, MC 3104, Berkeley, CA 94720-3104 and Garrison Sposito, gsposito@nature.berkeley.edu, Division of Ecosystem Sciences, University of California, 137 Mulford Hall #3114, Berkeley, CA 94720-3114.
Quinolone compounds have been shown to inhibit photosynthesis by targeting enzymes in the photosynthetic electron transport chain. It has been proposed recently that fluoroquinolone antibiotics may also inhibit photosynthesis. However, little is known about the specific inhibitory targets of these compounds in the photosynthetic electron transport chain and their mechanisms of action. Using structure-activity relationship (SAR) analysis, the structural components that may be responsible for photosynthetic inhibition and the potential targeted enzymes were identified. In vitro binding studies with isolated chloroplasts to monitor oxygen evolution and ADP phosphorylation were used to localize the inhibitory targets of ciprofloxacin, a prototypical fluoroquinolone, in the photosynthetic apparatus.