期刊
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
卷 233, 期 -, 页码 -出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.jphotobiol.2022.112499
关键词
Dual phototherapy; Photodynamic inactivation; Ciprofloxacin; E. coli; In vivo
资金
- Fundacao para a Ciencia e Tecnologia (FCT), QREN/FEDER [UIDB/00313/2020, PTDC/QUI-OUT/ 27996/2017]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [CEPOF 2013/07276-1]
- NCT 'BasicOptics and Applied to Life Sciences' [FAPESP 2014/50857-8, CNPq465360/2014-9]
- FAPESP [2018/07961-0, 2019/13569-8]
- FCT [PD/BD/143123/2019]
- Fundação para a Ciência e a Tecnologia [PTDC/QUI-OUT/27996/2017, PD/BD/143123/2019] Funding Source: FCT
This study investigates the influence of cationic imidazolyl-substituted photosensitizers and light on the activity of ciprofloxacin for inactivation of Escherichia coli. The results demonstrate that the optimized dual phototherapy protocol using these photosensitizers can reduce the amount of photosensitizer and ciprofloxacin required for full E. coli inactivation, and the combination therapy is superior to monotherapy in both in vitro and in vivo studies.
The emergence of new microorganisms with resistance to current antimicrobials is one of the key issues of modern healthcare that must be urgently addressed with the development of new molecules and therapies. Photodynamic inactivation (PDI) in combination with antibiotics has been recently regarded as a promising wide-spectrum therapy for the treatment of localized topical infections. However, further studies are required regarding the selection of the best photosensitizer structures and protocol optimization, in order to maximize the efficiency of this synergic interaction. In this paper, we present results that demonstrate the influence of the structure of cationic imidazolyl-substituted photosensitizers and light on the enhancement of ciprofloxacin (CIP) activity, for the inactivation of Escherichia coli. Structure-activity studies have highlighted the tetra cationic imidazolyl porphyrin IP-H-Me4+ at sub-bactericide concentrations (4-16 nM) as the most promising photosensitizer for combination with sub-inhibitory CIP concentration (<0.25 mg/L). An optimized dual phototherapy protocol using this photosensitizer was translated to in vivo studies in mice wounds infected with E. coli. This synergic combination reduced the amount of photosensitizer and ciprofloxacin required for full E. coli inactivation and, in both in vitro and in vivo studies, the combination therapy was clearly superior to each monotherapy (PDI or ciprofloxacin alone). Overall, these findings highlight the potential of cationic imidazolyl porphyrins in boosting the activity of antibiotics and lowering the probability of resistance development, which is essential for a sustainable long-term treatment of infectious diseases.
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