Drug Resistance in Cryptococcosis

Hanson, Kimberly E.; Catania, Jelena; Alexander, Barbara; Perfect, John R.

doi:10.1007/978-3-319-47266-9_20

Cited by 5 publications

(4 citation statements)

References 134 publications

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“…The gold standard induction treatment includes giving amphotericin B along with flucytosine [23]. However, this combination therapy has substantial side effects and the need for intravenous medications poses a problem, as these are not readily available in developing countries, which are most affected by cryptococcosis [24]. To overcome this problem, a combination of fluconazole along with flucytosine has been recommended after initial therapy with amphotericin B and flucytosine [1,23].…”

Section: Introductionmentioning

confidence: 99%

Distribution and Diversity of Cytochrome P450 Monooxygenases in the Fungal Class Tremellomycetes

Akapo

Padayachee

Chen

et al. 2019

IJMS

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Tremellomycetes, a fungal class in the subphylum Agaricomycotina, contain well-known opportunistic and emerging human pathogens. The azole drug fluconazole, used in the treatment of diseases caused by some species of Tremellomycetes, inhibits cytochrome P450 monooxygenase CYP51, an enzyme that converts lanosterol into an essential component of the fungal cell membrane ergosterol. Studies indicate that mutations and over-expression of CYP51 in species of Tremellomycetes are one of the reasons for fluconazole resistance. Moreover, the novel drug, VT-1129, that is in the pipeline is reported to exert its effect by binding and inhibiting CYP51. Despite the importance of CYPs, the CYP repertoire in species of Tremellomycetes has not been reported to date. This study intends to address this research gap. Comprehensive genome-wide CYP analysis revealed the presence of 203 CYPs (excluding 16 pseudo-CYPs) in 23 species of Tremellomycetes that can be grouped into 38 CYP families and 72 CYP subfamilies. Twenty-three CYP families are new and three CYP families (CYP5139, CYP51 and CYP61) were conserved across 23 species of Tremellomycetes. Pathogenic cryptococcal species have 50% fewer CYP genes than non-pathogenic species. The results of this study will serve as reference for future annotation and characterization of CYPs in species of Tremellomycetes.

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Section: Introductionmentioning

confidence: 99%

Distribution and Diversity of Cytochrome P450 Monooxygenases in the Fungal Class Tremellomycetes

Akapo

Padayachee

Chen

et al. 2019

IJMS

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“…Although the rates of cryptococcosis have dropped substantially since the development of highly active antiretroviral therapy, the mortality of HIV patients associated with cryptococcal meningitis remains high. One of the causes of treatment failure is the emergence of azole-resistant and -heteroresistant mutants (21–23).…”

Section: Introductionmentioning

confidence: 99%

In VitroActivity of a Novel Antifungal Compound, MYC-053, against Clinically Significant Antifungal-Resistant Strains ofCandida glabrata,Candida auris,Cryptococcus neoformans, andPneumocystisspp

Tetz

Collins

Vikina³

et al. 2019

Antimicrob Agents Chemother

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An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis species. MYC-053 was equally effective against the susceptible control strains, clinical isolates, and resistant strains, with MICs of 0.125 to 4.0 μg/ml. Notably, unlike other antifungals such as azoles, polyenes, and echinocandins, MYC-053 was effective against Pneumocystis isolates, therefore being the only synthetic antifungal that may potentially be used against Pneumocystis spp., Candida spp., and Cryptococcus spp. MYC-053 was highly effective against preformed 48-h-old C. glabrata and C. neoformans biofilms, with minimal biofilm eradication concentrations equal to 1 to 4 times the MIC. Together, these data indicated that MYC-053 may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi.

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“…The standard therapy for this disease is the use of amphotericin B (AMB), with or without flucytosine (5‐FC) and fluconazole (FLC). However, studies showed that these drugs have high failure rates, with the emergence of intrinsic resistance …”

Section: Introductionmentioning

confidence: 99%

In vitro combination between antifungals and diphenyl diselenide against Cryptococcus species

Rossato

Loreto

Venturini

et al. 2019

Mycoses

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Summary Cryptococcus species are an encapsulated fungal pathogen that cause cryptococcal meningitis. There are limited therapeutic options for this infection. The management includes the use of different antifungals such as amphotericin B, flucytosine, or fluconazole, either alone or in combination. However, numerous therapeutic failures, as well as the limited effectiveness of such therapeutics, have been described. Diphenyl diselenide is a chemically synthesised molecule with was found to have antimicrobial activity. In this study, we evaluated the antifungal activities of fluconazole, amphotericin B and flucytosine, in combination with diphenyl diselenide against 30 clinical isolates of Cryptococcus spp. using CLSI M27‐A3 method and the checkerboard microdilution technique. Our results show that the combination of flucytosine and diphenyl diselenide displayed 100% of synergism. However, when we analysed (PhSe)2 plus AMB or FLZ we observed around 70% of indifference. Our results suggest that the combination of diphenyl diselenide with other antifungal agents deserves attention as a new option for the development of alternative therapies for cryptococcosis.

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Drug Resistance in Cryptococcosis

Cited by 5 publications

References 134 publications

Distribution and Diversity of Cytochrome P450 Monooxygenases in the Fungal Class Tremellomycetes

Distribution and Diversity of Cytochrome P450 Monooxygenases in the Fungal Class Tremellomycetes

In VitroActivity of a Novel Antifungal Compound, MYC-053, against Clinically Significant Antifungal-Resistant Strains ofCandida glabrata,Candida auris,Cryptococcus neoformans, andPneumocystisspp

In vitro combination between antifungals and diphenyl diselenide against Cryptococcus species

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