Photodynamic inactivation of antibiotic resistant microorganisms based on natural pigment Hypericin

BACKGROUND AND OBJECTIVESOne of the most important public health threats of the present century is antibiotic resistance. Due to the inability of antibiotics for mutagenic strains, there is an incremental increase in hospital admission and death rates. In this regard, the development of novel therapeutic modalities may be effective in controlling antibiotic resistance increase. Antimicrobial photodynamic therapy (aPDT) has been suggested as an alternative to elude the use of drugs that cause resistance. The aPDT is a non-invasive method utilizing a combination of a nontoxic dye known as a photosensitizer, visible light, and molecular oxygen. The ROS produced after the excitation of photosensitizer by light at the appropriate wavelength react with cellular macromolecules leading to destroy pathogenic microorganisms. Hypericin (perihydroxylated perylene quinone-based) is a natural pigment extracted from plants of the genus Hypericium. This photosensitizer has low dark toxicity and a high quantum yield of singlet oxygen production which makes it a promising candidate for photodynamic therapy. This review aimed to give the latest results about the Hypericinmediated aPDT as a novel antimicrobial approach.MATERIALS AND METHODSThis study was a systematic search up to July ۲۰۲۳, using large citation databases, including Scopus, the Cochrane Library, Web of Science, and Pubmed, to review the investigations performed on photodynamic therapy with Hypericin in different in vitro and in vivo conditions. In addition, the potential of this procedure for the treatment of antibiotic-resistant microbial infections was evaluated. RESULTS AND DISCUSSIONThe different studies have indicated that Hypericin has a strong potential to photoinactivate many microbes in planktonic and biofilm forms. Hypericin-based PDT exerts its antimicrobial effect both by direct destruction of microorganisms and the activation of the host's innate immune system. The increase of Hypericin concentration as well as a high light dose used for Hypericin photoactivation improves the efficacy of aPDT. The findings showed that Gram-positive strains such as Staphylococcus sp. and Enterococcus spp. are more susceptible to aPDT than Gram-negative bacteria including Klebsiella pneumoniae and E. coli. Several articles reported that Hypericin shows significant cytotoxic activity against methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) S. aureus isolates. In the main, the induction of cell death after aPDT is due to the overproduction of ROS inside the cells, resulting in severe plasma membrane damage and photooxidation of important biomacromolecules. The results of different studies indicated that Hypericin had an inhibition effect on the transcriptional regulator SarA expression and increased β-lactam efficiency in MRSA. Recent reports also showed that this photosensitize can significantly decrease the minimum inhibitor concentrations of used antibiotics, especially at lower lightdoses. Compared to other natural photosensitizers, Hypericin presents a more effective antimicrobial effect, because some studies showed that it inhibited E. coli growth to ۹۹.۹% after photoactivation with a light dose of ۶ J/cm۲, while curcumin achieved suppression of the growth of bacteria with ۹۰% efficacy after using light doses higher than ۱۰ J/cm۲.CONCLUSIONBased on the current literature, it can be concluded that Hypericin-mediated aPDT can be considered a promising approach to cure antibiotic-resistant microbial diseases.

کلیدواژه ها:

Hypericin ، Antimicrobial approach ، Photodynamic therapy ، Antibiotic resistance