State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University, 610064, Chengdu, China.
Analytical & Testing Center, Sichuan University, 610064, Chengdu, China.
Nat Commun. 2021 Jan 22;12(1):526. doi: 10.1038/s41467-020-20869-8.
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 (IC) 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.
能够在极端酸性条件（pH < 4.0）下生存的耐酸菌对当前的抗菌方法，包括抗生素和光动力细菌失活（PDI），构成了挑战。在这里，我们提出了一种基于荧光素卤化的光动力失活极端酸性条件下的光敏剂设计概念。卤化后，控制荧光素吸收的著名螺环化反应转移到酸性 pH 范围。同时，卤素的重原子效应促进了单线态氧的生成。因此，我们发现了几种能够在 pH < 2.0 的条件下工作的光敏剂，适用于广泛的耐酸菌家族，其半最大抑制浓度（IC）低于 1.1 μM。由于其中一种发现的光敏剂是美国食品和药物管理局批准的食品添加剂（2'，4'，5'，7'-四碘荧光素，TIF），因此成功地抑制了酸性饮料中的细菌生长，将保质期从 2 天延长到约 15 天。此外，还在极端酸性条件下用 TIF 进行了体内念珠菌 PDI 实验。
