Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies

Abstract

Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective therapeutic modality to eradicate drug resistant bacteria without provoking multidrug resistance, has attracted increasing attention. This study examined the antimicrobial efficacy of the novel cationic amino acid-porphyrin conjugate 4I with four lysine groups against two different clinical isolated strains (drug sensitive and multidrug resistant) of the Acinetobacter baumannii species and its toxicity on murine dermal fibroblasts in vitro, as well as the therapeutic effect of PACT on acute, potentially lethal multidrug resistant strain excisional wound infections in vivo. The PACT protocol exposed 4I to illumination, exhibiting high antimicrobial efficacy on two different strains due to a high yield of reactive oxygen species (ROS) and non-selectivity to microorganisms. The photoinactivation effects of 4I against two different strains were dose-dependent. At 3.9 μM and 7.8 μM, PACT induced 6 log units of inactivation of sensitive and multidrug resistant strains. In contrast, 4I alone and illumination alone treatments had no visibly antimicrobial effect. Moreover, cytotoxicity tests revealed the great safety of the photosensitizer 4I in mice. In the in vivo study, we found 4I-mediated PACT was not only able to kill bacteria but also accelerated wound recovery. Compared with non-treated mice, over 2.89 log reduction of multidrug resistant Acinetobacter baumannii strain was reached in PACT treat mice at 24 h post-treatment. These results imply that 4I-mediated PACT therapy is an effective and safe alternative to conventional antibiotic therapy and has clinical potential for superficial drug-resistant bacterial infections.

Antimicrobials Are a Photodynamic Inactivation Adjuvant for the Eradication of Extensively Drug-Resistant Acinetobacter baumannii

“…The significant bactericidal efficacy of both aBL and aPDI against A. baumannii was repeatedly reported in numerous published in vitro and in vivo studies (Dai et al, 2009; Huang et al, 2014; Maisch et al, 2014; Zhang et al, 2014; Yuan et al, 2017; Yang et al, 2018). However, the first published evidence of a combined aPDI/antibiotic approach being used against pandrug-resistant A. baumannii was presented by Boluki et al (2017).…”

“…A lack of effective antimicrobials has forced the need for the development of novel strategies to control A. baumannii infections. One of these approaches is antimicrobial photodynamic inactivation (aPDI) or antimicrobial blue light (aBL) (Nitzan et al, 1998; Dai et al, 2009; Cai et al, 2012; Huang et al, 2014; Yuan et al, 2017; Yang et al, 2018). These strategies exert high bactericidal efficacy toward various microbes regardless of antibiotic resistance.…”

Properties of halogenated and sulfonated porphyrins relevant for the selection of photosensitizers in anticancer and antimicrobial therapies

“…poly-L-lysine) porphyrin derivatives tend to have a superior activity towards microbial species and a relative selectivity over host mammalian cells, enabled by increased binding and penetration through the negatively charged bacteria outer barrier [ 2 , 10 – 12 ]. The ability of the cytotoxic agents to preferentially target bacteria over healthy mammalian cells can be also achieved by specific conjugation with antimicrobial peptides [ 13 ]. Interesting biological properties have also been reported for various non-tetrapyrrolic compounds with different molecular frameworks [ 14 , 15 ], such as functionalized fullerenes that act not only as highly effective PDI agents but also as antiretroviral dyes in cells, or benzo[ a ]phenoxazine chalcogen analogues that were proposed as broad-spectrum antimicrobial agents [ 16 – 18 ].…”

Porphyrinoid biohybrid materials as an emerging toolbox for biomedical light management

“…Ding and co-workers also studied the antimicrobial efficacy of Lys-H 2 Por, in this case against different strains of Acinetobacter baumannii, showing good results both in vitro and in vivo. 44 In a different approach, Serra et al synthesized four H 2 Por-AA conjugates with glycine, serine, tyrosine and methionine. 45 Biological assays were performed in vitro, against tumoral (HeLa) and non-tumoral (HaCaT) human cell lines.…”