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1.
J Infect Dis ; 221(4): 618-626, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31565732

RESUMO

BACKGROUND: Antimicrobial resistance is a significant concern to public health, and there is a pressing need to develop novel antimicrobial therapeutic modalities. METHODS: In this study, we investigated the capacity for quinine hydrochloride (Q-HCL) to enhance the antimicrobial effects of antimicrobial blue light ([aBL] 405 nm wavelength) against multidrug-resistant (MDR) Gram-negative bacteria in vitro and in vivo. RESULTS: Our findings demonstrated the significant improvement in the inactivation of MDR Pseudomonas aeruginosa and Acinetobacter baumannii (planktonic cells and biofilms) when aBL was illuminated during Q-HCL exposure. Furthermore, the addition of Q-HCL significantly potentiated the antimicrobial effects of aBL in a mouse skin abrasion infection model. In addition, combined exposure of aBL and Q-HCL did not result in any significant apoptosis when exposed to uninfected mouse skin. CONCLUSIONS: In conclusion, aBL in combination with Q-HCL may offer a novel approach for the treatment of infections caused by MDR bacteria.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/efeitos da radiação , Antibacterianos/uso terapêutico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos da radiação , Quinina/uso terapêutico , Terapia Ultravioleta/métodos , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/efeitos da radiação , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos da radiação , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Plâncton/microbiologia , Pseudomonas aeruginosa/fisiologia , Quinina/farmacologia , Pele/lesões , Pele/microbiologia , Pele/patologia , Resultado do Tratamento , Ferimentos e Lesões/microbiologia
2.
J Infect Dis ; 220(5): 873-881, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-30629196

RESUMO

Antimicrobial resistance in Neisseria gonorrhoeae is a major issue of public health, and there is a critical need for the development of new antigonococcal strategies. In this study, we investigated the effectiveness of antimicrobial blue light (aBL; wavelength, 405 nm), an innovative nonpharmacological approach, for the inactivation of N. gonorrhoeae. Our findings indicated that aBL preferentially inactivated N. gonorrhoeae, including antibiotic-resistant strains, over human vaginal epithelial cells in vitro. Furthermore, no aBL-induced genotoxicity to the vaginal epithelial cells was observed at the radiant exposure used to inactivate N. gonorrhoeae. aBL also effectively inactivated N. gonorrhoeae that had attached to and invaded into the vaginal epithelial cells in their cocultures. No gonococcal resistance to aBL developed after 15 successive cycles of inactivation induced by subtherapeutic exposure to aBL. Endogenous aBL-activatable photosensitizing porphyrins in N. gonorrhoeae were identified and quantified using ultraperformance liquid chromatography, with coproporphyrin being the most abundant species in all N. gonorrhoeae strains studied. Singlet oxygen was involved in aBL inactivation of N. gonorrhoeae. Together, these findings show that aBL represents a potential potent treatment for antibiotic-resistant gonococcal infection.


Assuntos
Gonorreia/radioterapia , Neisseria gonorrhoeae/efeitos da radiação , Abetalipoproteinemia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos da radiação , Células Epiteliais/microbiologia , Feminino , Gonorreia/tratamento farmacológico , Humanos , Luz , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/crescimento & desenvolvimento , Oxigênio , Azida Sódica , Vagina/microbiologia
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