Inhibition of Photosynthesis by a Fluoroquinolone Antibiotic

摘要

Recent microcosm studies have revealed that fluoroquinolone (FQ) antibiotics can have ecotoxicological impacts on photosynttietic organisms, but little is known about the mechanisms of toxicity. We employed a combination of modeling and experimental techniques to explore how FQs may have these unintended secondary toxic effects. Structure-activity analysis revealed that the quinolone ring and secondary amino group typically present in FQ antibiotics may mediate their action as quinone site inhibitors in photosystem II (PS-II), a key enzyme in photosynthetic electron transport. Follow-up molecular simulations involving nalidixic acid (Naldx), a nonfluorinated quinolone with a demonstrated adverse impact on photosynthesis, and ciprofloxacin (Cipro), the most commonly used FQ antibiotic, showed that both may interfere stereochemically with the catalytic activity of reaction center II (RC-III, the pheophytin-quinone-type center present in PS-II. Naldx can occupy the same binding site as the secondary quinone acceptor (Q_B) in RC-II and interact with amino acid residues required for the enzymatic reduction of Q_b. Cipro binds in a somewhat different manner, suggesting a different mechanism of interference. Fluorescence induction kinetics, a common method of screening for PS-II inhibition, recorded for photoexcited thylakoid membranes isolated from Cipro-exposed spinach chloroplasts, indicated that Cipro interferes with the transfer of energy from excited antenna chlorophyll molecules to the reaction center in RC-II ([Cipro] ≥ 5 μM in vitro and ≥10 μM in vivo) and thus delays the kinetics of photoreduction of the primary quinone acceptor (Q_a; [Cipro] ≥ 0.6 μM in vitro). Spinach plants exposed to Cipro exhibited severe growth inhibition characterized by a decrease in both the synthesis of leaves and growth of the roots ([Cipro] ≥ 0.5 μM in vivo). Our results thus demonstrate that Cipro and related FQ antibiotics may interfere with photosynthetic pathways, in addition to causing morphological deformities in higher plants.