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 N-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 E. coli and S. aureus 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.

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合成阳离子铁卟啉的抗菌活性

广泛的抗生素耐药性要求采取新的对抗感染的策略。基于卟啉的化合物很早以前就被引入作为光敏剂用于光动力疗法，但尚未系统地探索此类化合物的光依赖性抗菌活性。这项研究的结果表明，合成的阳离子两亲铁N-烷基吡啶基卟啉在低至5μM的浓度下具有很强的杀菌作用。实验动物良好耐受的铁卟啉FeTnHex-2-PyP有效杀死了革兰氏阴性和革兰氏阳性微生物。它的杀菌活性是不依赖氧的，并且受化合物的亲脂性和在细菌细胞中的积累的控制。这种行为与阴离子镓原卟啉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的活性受氧化还原循环的破坏而受到限制。从铁卟啉释放的铁或其他分解产物都不是杀菌活性的原因。FeTnHex-2-PyP对抗生素敏感的大肠杆菌和金黄色葡萄球菌相对于其抗生素抗性对应物。我们的数据表明，两性带正电荷的金属卟啉的开发可能是引进新的抗抗生素菌株的有前途的方法。