Selective photoinactivation of Candida albicans in the non-vertebrate host infection model Galleria mellonella

Abstract

BackgroundCandida spp. are recognized as a primary agent of severe fungal infection in immunocompromised patients, and are the fourth most common cause of bloodstream infections. Our study explores treatment with photodynamic therapy (PDT) as an innovative antimicrobial technology that employs a nontoxic dye, termed a photosensitizer (PS), followed by irradiation with harmless visible light. After photoactivation, the PS produces either singlet oxygen or other reactive oxygen species (ROS) that primarily react with the pathogen cell wall, promoting permeabilization of the membrane and cell death. The emergence of antifungal-resistant Candida strains has motivated the study of antimicrobial PDT (aPDT) as an alternative treatment of these infections. We employed the invertebrate wax moth Galleria mellonella as an in vivo model to study the effects of aPDT against C. albicans infection. The effects of aPDT combined with conventional antifungal drugs were also evaluated in G. mellonella.ResultsWe verified that methylene blue-mediated aPDT prolonged the survival of C. albicans infected G. mellonella larvae. The fungal burden of G. mellonella hemolymph was reduced after aPDT in infected larvae. A fluconazole-resistant C. albicans strain was used to test the combination of aPDT and fluconazole. Administration of fluconazole either before or after exposing the larvae to aPDT significantly prolonged the survival of the larvae compared to either treatment alone.ConclusionsG. mellonella is a useful in vivo model to evaluate aPDT as a treatment regimen for Candida infections. The data suggests that combined aPDT and antifungal therapy could be an alternative approach to antifungal-resistant Candida strains.

Antimicrobial photodynamic therapy with phenothiazinium photosensitizers in non-vertebrate model Galleria mellonella infected with Fusarium keratoplasticum and Fusarium moniliforme

“…This model of infection has the potential to facilitate the in vivo study of pathogen-host cross talk (Chibebe Junior et al, 2013). We previously showed the in vitro efficacy of APDT with MB, NMBN and S137 against microconidia of F. keratoplasticum (F. solani species complex) and F. moniliforme (de Menezes et al, 2016).…”

Non‐mammalian Hosts and Photobiomodulation: Do All Life‐forms Respond to Light?

“…Larvae of the greater wax moth Galleria mellonella have recently been used as model hosts for studying pathogenic microorganisms as an alternative to vertebrate animals . The model has been used to study microbial virulence and pathogenesis by such species as Candida albicans, Cryptococcus neoformans and Enterococcus faecalis (), and has been used to study new therapies such as antimicrobial photodynamic inactivation .…”

Dissecting Candida albicans Infection from the Perspective of C. albicans Virulence and Omics Approaches on Host–Pathogen Interaction: A Review

“…On the other hand, the C. elegans model has also often been used in the screening and development of new antifungal chemical compounds [81], to study Candida virulence factors [68], and to examine antifungal innate immunity [82]. Like the D. melanogaster and C. elegans models, the G. mellonella model has been employed in many studies, including experiments on Candida albicans mutants and virulence [83,84], Candida virulence factors [85,86,87], C. albicans virulence transcriptional factors [88], photodynamic therapy (PDT) as a treatment regimen for Candida infections [89], and the evaluation of the efficacy of antifungal agents [90]. Overall, the adoption of these mini-hosts in C. albicans infection studies provides a number of advantages.…”