Infections due to emerging and uncommon medically important fungal pathogens

Walsh, Thomas J.; Groll, Andreas H.; Hiemenz, John W.; Fleming, Rhonda; Roilides, Emmanuel; Anaissie, Elias

doi:10.1111/j.1470-9465.2004.00839.x

Cited by 522 publications

(434 citation statements)

References 177 publications

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“…Because the filamentous fungal pathogens are relatively resistant to the current antimycotic drugs (26), alternative treatment strategies are urgently needed, and the use of DLD as an antifungal agent could open new therapeutic avenues.…”

Section: Discussionmentioning

confidence: 99%

Drosomycin-Like Defensin, a Human Homologue ofDrosophila melanogasterDrosomycin with Antifungal Activity

Simon

Kullberg²,

Tripet

et al. 2008

Antimicrob Agents Chemother

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Innate antifungal defense in Drosophila melanogaster relies on the activation of the Toll molecule and the release of drosomycin, a defensin-like molecule with antifungal properties. Ten human homologues of Toll have been described, with central roles in activation of the innate host defense. In the present study, we report a putative human homologue of the Drosophila-derived drosomycin, designated drosomycin-like defensin (DLD). Synthetic DLD displays a broad spectrum of activity against Aspergillus spp. and other clinically relevant filamentous fungi. These effects are specific for filamentous fungi; no activity has been found against yeasts or gram-positive or gram-negative bacteria. Synthetic DLD also displays immunomodulatory effects on Aspergillus-stimulated cytokine production. In addition, we show the expression of DLD mRNA in several human tissues, particularly in the skin, consistent with its putative role as a defensin against invading microorganisms. This is the first indication of an endogenous human peptide with specific antifungal activity, which is probably central in the defense against infections with molds.Drosophila melanogaster, like other insects, relies on both cellular and humoral mechanisms to mount its antimicrobial host defense. The mainstay of its humoral defense is the injuryinduced secretion of an array of antimicrobial peptides by the fat body, the functional equivalent of the liver (9, 10). To date, seven distinct families of antimicrobial peptides from immunechallenged Drosophila flies have been characterized, each with a specific spectrum of activity. Among these peptides, drosomycin is highly active against filamentous fungi, protecting Drosophila from infections by Aspergillus fumigatus, whereas no activity against gram-positive or gram-negative bacteria has been found (9). The release of drosomycin is under the control of signals mediated by Toll, a transmembrane receptor activated by a cytokine-like protein, Spaetzle (16).Comparison of the Toll complex with that of mammalian innate defense mechanisms has revealed that the intracellular tail of Toll shows a striking homology with the intracellular domain of interleukin-1 receptor type I (IL-1RI), later designated the Toll/IL-1R (TIR) domain (23). Moreover, the intracellular signaling pathway induced by Drosophila Toll is highly similar to the intracellular pathways activated by IL-1RI (12). Eleven different Toll-like receptors (TLRs) have been identified in mammals and have been demonstrated to be crucial for the recognition of pathogenic microorganisms and the activation of the innate immune response in general (24), including antifungal defense (2, 20, 21). Where Toll activation leads to the direct release of drosomycin, engagement of TLRs induces the release of cytokines and ␣-and ␤-defensins (4, 6), but to date no human homologue of drosomycin has been reported.In the present study, we report a putative human peptide with high homology with drosomycin, and we demonstrate potent antifungal properties for this peptide, desi...

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Section: Discussionmentioning

confidence: 99%

Drosomycin-Like Defensin, a Human Homologue ofDrosophila melanogasterDrosomycin with Antifungal Activity

Simon

Kullberg²,

Tripet

et al. 2008

Antimicrob Agents Chemother

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“…This is a big challenge in developing countries including Tanzania (Leung et al, 2011;'t Hoen et al, 2014). To aggravate the situation further, the pharmaceutical industries are not enthusiastic anymore to invest in this line despite the fact that there is a lot of new emerging infections due HIV and AIDS (Walsh et al, 2004;Leung et al, 2011;White, 2011).…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Activity of Propolis From Tabora and Iringa Regions, Tanzania and Synergism with Gentamicin

Runyoro¹,

Ngassapa²,

Kamugisha³

2017

J App Pharm Sci

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Antimicrobial resistance (AMR) is among the threats to global public health, with developing countries being mostly affected. The AMR has undermined development of new antimicrobial agents by pharmaceutical industries despite new emerging infections. This necessitates a search for antimicrobial agents from resources available in developing countries. This study, therefore, aimed at assessing antimicrobial activity of two propolis samples from Iringa and Tabora, Tanzania. Ethanolic extracts of the two propolis samples were tested against standard microorganisms including, Gram +ve and Gram -ve bacteria and yeasts by determination of MICs using broth microdilution method. Synergism with Gentamicin was also assessed for one of the samples. Furthermore, HPTLC profiles of the extracts and presence of flavonoids were determined. The two propolis samples exhibited varied activity against the tested microorganisms with MICs ranging from 0.42 to 6.67mg/ml, with Tabora propolis being more active than Iringa propolis. Staphylococcus aureus was the most susceptible microorganism, while Pseudomonas aeruginosa was the most resistant. Propolis also potentiated the activity of Gentamicin. Both samples tested positive for flavonoids. However, there were some differences in their HPTLC profiles. We recommend further studies involving more samples of propolis from various regions of Tanzania to verify further the observed activity and synergism.

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“…2 They belong to the human microbiome, as colonizers of the gastrointestinal and oral cavities, male perigenital skin (scrotal, perianal, and inguinal sites of the body) and temporarily inhabiting the respiratory tract and skin. [3][4][5][6][7][8][9][10][11][12] It is not clear how Trichosporonosis can be acquired, but the following possibilities can be envisaged: (i) poor hygiene, (ii) bathing in contaminated water, (iii) sexual transmission, (iv) hair humidity and the length of the scalp hair (more specifically in the case of acquiring white piedra), (v) gastrointestinal colonization and further translocation throughout the gut (deep-seated infections), and (vi) exogenously acquired through a percutaneously inserted intravascular catheter via colonized skin. [13][14][15][16][17][18] In spite of the fact that Trichosporon spp are probably the second or third most common non-Candida yeast infections causing invasive disease in patients with hematological cancer, there are few reports related to virulence factors of this genus.…”

Section: Introductionmentioning

confidence: 99%

The development of animal infection models and antifungal efficacy assays against clinical isolates ofTrichosporon asahii,T. asteroidesandT. inkin

et al. 2015

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The present study developed Galleria mellonella and murine infection models for the study of Trichosporon infections. The utility of the developed animal models was demonstrated through the assessment of virulence and antifungal efficacy for 7 clinical isolates of Trichosporon asahii, T. asteroides and T. inkin. The susceptibility of the Trichosporon isolates to several common antifungal drugs was tested in vitro using the broth microdilution and the Etest methods. The E-test method depicted a lower minimal inhibitory concentration (MIC) for amphotericin and a slightly higher MIC for caspofungin, while MICs observed for the azoles were different but comparable between both methods. All three Trichosporon species established infection in both the G. mellonella and immunosuppressed murine models. Species and strain dependent differences were observed in both the G. mellonella and murine models. T. asahii was demonstrated to be more virulent than the other 2 species in both animal hosts. Significant differences in virulence were observed between strains for T. asteroides in the murine model. In both animal models, fluconazole and voriconazole were able to improve the survival of the animals compared to the untreated control groups infected with any of the 3 Trichosporon species. In G. mellonella, amphotericin was not able to reduce mortality in any of the 3 species. In contrast, amphotericin was able to reduce murine mortality in the T. asahii or T. inkin models, respectively. Hence, the developed animal infection models can be directly applicable to the future deeper investigation of the molecular determinants of Trichosporon virulence and antifungal resistance.

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Infections due to emerging and uncommon medically important fungal pathogens

Cited by 522 publications

References 177 publications

Drosomycin-Like Defensin, a Human Homologue ofDrosophila melanogasterDrosomycin with Antifungal Activity

Drosomycin-Like Defensin, a Human Homologue ofDrosophila melanogasterDrosomycin with Antifungal Activity

Antimicrobial Activity of Propolis From Tabora and Iringa Regions, Tanzania and Synergism with Gentamicin

The development of animal infection models and antifungal efficacy assays against clinical isolates ofTrichosporon asahii,T. asteroidesandT. inkin

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