Immune-Deficient <i>Drosophila melanogaster</i>: A Model for the Innate Immune Response to Human Fungal Pathogens

Alarco, Anne‐Marie; Marcil, Anne; Chen, Jian; Suter, Beat; Thomas, David Y.; Whiteway, Malcolm

doi:10.4049/jimmunol.172.9.5622

Cited by 123 publications

(104 citation statements)

References 60 publications

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“…Flies deprived of a functional Toll pathway succumb to C. glabrata infection, thus highlighting again the primary role of the Toll pathway in systemic antifungal host defense (18,21,22,46). The inoculum size of C. glabrata we used did not induce a high mortality in wild-type flies in this systemic infection model for at least a period of 2 wk (data not shown).…”

Section: Glabrata Persist Even In Wild-type Fliesmentioning

confidence: 93%

“…Flies deficient for the evolutionarily conserved Toll signaling pathway are sensitive to fungal infections (18,21,22). The Toll pathway of D. melanogaster controls the systemic antifungal and the Gram-positive antibacterial host response, whereas immune deficiency (IMD), a second NF-kB-like pathway, is involved in the host response against Gram-negative bacteria infection.…”

mentioning

confidence: 99%

“…17). D. melanogaster is an excellent tool for the identification of novel virulence genes, for medium-throughput screening of antifungal molecules against Candida species, and for investigating pathogenicity of C. albicans (18)(19)(20).…”

mentioning

confidence: 99%

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The Drosophila Toll Pathway Controls but Does Not Clear Candida glabrata Infections

Quintin

Asmar

Matskevich

et al. 2013

The Journal of Immunology

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The pathogenicity of Candida glabrata to patients remains poorly understood for lack of convenient animal models to screen large numbers of mutants for altered virulence. In this study, we explore the minihost model Drosophila melanogaster from the dual perspective of host and pathogen. As in vertebrates, wild-type flies contain C. glabrata systemic infections yet are unable to kill the injected yeasts. As for other fungal infections in Drosophila, the Toll pathway restrains C. glabrata proliferation. Persistent C. glabrata yeasts in wild-type flies do not appear to be able to take shelter in hemocytes from the action of the Toll pathway, the effectors of which remain to be identified. Toll pathway mutant flies succumb to injected C. glabrata. In this immunosuppressed background, cellular defenses provide a residual level of protection. Although both the Gram-negative binding protein 3 pattern recognition receptor and the Persephone protease-dependent detection pathway are required for Toll pathway activation by C. glabrata, only GNBP3, and not psh mutants, are susceptible to the infection. Both Candida albicans and C. glabrata are restrained by the Toll pathway, yet the comparative study of phenoloxidase activation reveals a differential activity of the Toll pathway against these two fungal pathogens. Finally, we establish that the high-osmolarity glycerol pathway and yapsins are required for virulence of C. glabrata in this model. Unexpectedly, yapsins do not appear to be required to counteract the cellular immune response but are needed for the colonization of the wild-type host.

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Section: Glabrata Persist Even In Wild-type Fliesmentioning

confidence: 93%

mentioning

confidence: 99%

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The Drosophila Toll Pathway Controls but Does Not Clear Candida glabrata Infections

Quintin

Asmar

Matskevich

et al. 2013

The Journal of Immunology

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“…Regarding SC5314, the effect of (Fonzi & Irwin, 1993), 90028 (Espinel-Ingroff et al, 1992, 3153A (Evans et al, 1974), 2-76 , FH1 (Marr et al, 1997), AF293 (Nierman et al, 2005), H99 (Franzot et al, 1999) and D665-1A (Alarco et al, 2004). dMICs were determined by Etests (see Methods).…”

Section: B G Oliver and Othersmentioning

confidence: 99%

Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi

et al. 2008

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The tetracycline (TET) promoter has been used in several systems as an inducible regulator of gene expression. In control analyses, the standard Candida albicans laboratory strain SC5314 was found to have altered susceptibility to a variety of antifungal drugs in the presence of relatively high concentrations (50-200 mg ml "1 ) of TET. Altered susceptibility was most notable with exposure to amphotericin B (AMB), with a 32-fold increase in susceptibility, and terbinafine (TRB), with a 32-fold decrease in susceptibility. The TET/AMB synergy was observed in several clinical isolates of C. albicans and in the distantly related species Aspergillus fumigatus and Cryptococcus neoformans. The TET/AMB synergy is not related to efflux pump activity, as determined by FACS analyses and by analysis of a strain containing efflux pump deletions. Gene expression analyses by luciferase and by quantitative real-time reverse transcriptase PCR failed to identify significant alterations in expression of any genes associated with resistance. C. albicans grown with TET for 48 h does show a reduction in total cellular ergosterol. Analysis of growth curves suggests that the TET effect is associated with lack of a diauxic shift, which is related to a loss of mitochondrial function. MitoTracker fluorescent dye was used to demonstrate that TET has a direct effect on mitochondrial function. These results demonstrate the need for careful analysis of TET effects when using a TET-inducible promoter, especially in studies that involve antifungal drugs. This study defines some limits to the use of the TET-inducible promoter, and identifies effects on cells that are the result of TET exposure alone, not the result of expression of a targeted gene.

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“…Its fast growth, short life cycle, ease of manipulation, low cost and simplicity of ethical and regulatory issues, make it an attractive host for such studies, and its immune system is similar in some ways to the mammalian innate immune system 12,23,24,27,28 .…”

Section: Drosophila As a Model System For Host-pathogen Interactionsmentioning

confidence: 99%

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2017

IJPSR

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ABSTRACT:Probiotics have been used to protect hosts from pathogens of gastrointestinal and reproductive systems, but their ability to protect against systemic pathogens is largely unexplored. In this study we ask whether orally administered bacteria and yeasts can protect Drosophila melanogaster against the opportunistic fungal pathogen Aspergillus flavus. Flies were fed an artificial diet mixed with live microorganisms for one day prior to infection with A. flavus, and mortality was recorded every day for 8 days. Seven microorganisms were tested; of these, Bacillus cereus (ATCC 13061), Candida inconspicua, Issatchenkia hanoiensis, and Klebsiella sp. significantly decreased mortality of flies subsequently infected with A. flavus compared to controls infected with A. flavus alone. Heat-killed microorganisms did not protect flies, suggesting that the probiotic effect observed was not caused by improved nutrition. D. melanogaster is a good model organism to study microbial interactions with hosts and test the effects of potential probiotics against pathogens.

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Immune-Deficient Drosophila melanogaster: A Model for the Innate Immune Response to Human Fungal Pathogens

Cited by 123 publications

References 60 publications

The Drosophila Toll Pathway Controls but Does Not Clear Candida glabrata Infections

The Drosophila Toll Pathway Controls but Does Not Clear Candida glabrata Infections

Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi

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