Halo-fluorescein for photodynamic bacteria inactivation in extremely acidic conditions

Aciduric bacteria that can survive in extremely acidic conditions (pH < 4.0) are challenging to the current antimicrobial approaches, including antibiotics and photodynamic bacteria inactivation (PDI). Here, we communicate a photosensitizer design concept of halogenation of fluorescein for extremely acidic PDI. Upon halogenation, the well-known spirocyclization that controls the absorption of fluorescein shifts to the acidic pH range. Meanwhile, the heavy atom effect of halogens boosts the generation of singlet oxygen. Accordingly, several photosensitizers that could work at even pH < 2.0 were discovered for a broad band of aciduric bacteria families, with half maximal inhibitory concentrations (IC₅₀) lower than 1.1 μM. Since one of the discovered photosensitizers is an FDA-approved food additive (2',4',5',7'-tetraiodofluorescein, TIF), successful bacteria growth inhibition in acidic beverages was demonstrated, with greatly extended shelf life from 2 days to ~15 days. Besides, the in vivo PDI of Candidiasis with TIF under extremely acidic condition was also demonstrated.