Abstract
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.
Highlights
In a recent report, the WHO pointed to antimicrobial resistance as a global problem that poses a threat for the management of diseases caused by viruses, bacteria, and fungi [1]
At 3.0 μM, the most hydrophilic FeP, FeTE-2-PyP, completely prevented cell proliferation, while the amphiphilic hexyl derivative FeTnHex-2-PyP only decreased the rate of cell proliferation, while the amphiphilic hexyl derivative FeTnHex-2-PyP only decreased the rate of growth
FeTnHex-2-PyP or FeTnOct-2-PyP (Figure 3). These results show that the amphiphilic hexyl and octyl derivatives exerts much stronger bactericidal action than the hydrophilic ethyl analog
Summary
The WHO pointed to antimicrobial resistance as a global problem that poses a threat for the management of diseases caused by viruses, bacteria, and fungi [1]. The number of antibiotic-resistant bacterial strains is increasing all over the world, which potentially may lead to a point when infections would become untreatable with currently available drugs. The routine answer to this problem has been the introduction of new antibiotics that overcome bacterial resistance. A drop in the research and introduction of new antibiotics has been observed [2,3,4]. Patients with infections due to antimicrobial-resistant organisms cost the health care system much more than patients infected with antimicrobial-susceptible pathogens [5].
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