Tovmasyan Artak, Batinic-Haberle Ines, Benov Ludmil
Division of Neurobiology, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Department of Radiation Oncology, Duke University School of Medicine, Durham, NC 27710, USA.
Antioxidants (Basel). 2020 Oct 10;9(10):972. doi: 10.3390/antiox9100972.
Widespread antibiotic resistance demands new strategies for fighting infections. Porphyrin-based compounds were long ago introduced as photosensitizers for photodynamic therapy, but light-independent antimicrobial activity of such compounds has not been systematically explored. The results of this study demonstrate that synthetic cationic amphiphilic iron -alkylpyridylporphyrins exert strong bactericidal action at concentrations as low as 5 μM. Iron porphyrin, FeTnHex-2-PyP, which is well tolerated by laboratory animals, efficiently killed Gram-negative and Gram-positive microorganisms. Its bactericidal activity was oxygen-independent and was controlled by the lipophilicity and accumulation of the compound in bacterial cells. Such behavior is in contrast with the anionic gallium protoporphyrin IX, whose efficacy depends on cellular heme uptake systems. Under aerobic conditions, however, the activity of FeTnHex-2-PyP was limited by its destruction due to redox-cycling. Neither iron released from the Fe-porphyrin nor other decomposition products were the cause of the bactericidal activity. FeTnHex-2-PyP was as efficient against antibiotic-sensitive and as against their antibiotic-resistant counterparts. Our data demonstrate that development of amphiphilic, positively charged metalloporphyrins might be a promising approach in the introduction of new weapons against antibiotic-resistant strains.
广泛存在的抗生素耐药性需要新的抗感染策略。基于卟啉的化合物早在很久以前就被用作光动力疗法的光敏剂，但此类化合物与光无关的抗菌活性尚未得到系统研究。本研究结果表明，合成的阳离子两亲性铁 - 烷基吡啶卟啉在低至5 μM的浓度下就能发挥强大的杀菌作用。铁卟啉FeTnHex - 2 - PyP对实验动物耐受性良好，能有效杀灭革兰氏阴性菌和革兰氏阳性菌。其杀菌活性不依赖氧气，且受化合物在细菌细胞中的亲脂性和积累情况控制。这种行为与阴离子型原卟啉镓IX相反，后者的功效取决于细胞血红素摄取系统。然而，在有氧条件下，FeTnHex - 2 - PyP的活性因氧化还原循环导致的破坏而受到限制。从铁卟啉中释放出的铁以及其他分解产物都不是杀菌活性的原因。FeTnHex - 2 - PyP对抗生素敏感菌和耐药菌同样有效。我们的数据表明，开发两亲性、带正电荷的金属卟啉可能是引入对抗耐药菌株新武器的一种有前景的方法。
