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ERG2 and ERG24 are required for normal vacuolar physiology as well as candida albicans pathogenicity in a murine model of disseminated but not vaginal candidiasis.

Luna Tapia, Arturo; Peters, Brian M.; Eberle, Karen E.; Kerns, Morgan E.; Palmer, Glen E.; Foster, Timothy P.; Marrero, Luis; Noverr, Mairi C.; Fidel , Paul L. (Estados Unidos: Eukaryotic Cell, 2015., 2019-10-01)

Several important classes of antifungal agents, including the azoles, act by blocking ergosterol biosynthesis. It was recently reported that the azoles cause massive disruption of the fungal vacuole in the prevalent human ...
Three prevacuolar compartment Rab GTPases impact candida albicans hyphal growth.

Johnston, Douglas A.; Luna Tapia, Arturo; Eberle, Karen E.; Palmer, Glen E. (Estados Unidos: Eukaryotic Cell , 2013., 2019-10-03)

Disruption of vacuolar biogenesis in the pathogenic yeast Candida albicans causes profound defects in polarized hyphal growth. However, the precise vacuolar pathways involved in yeast-hypha differentiation have not been ...
Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals.

Luna Tapia, Arturo; Kerns, Morgan E.; Jursic, Branko S.; Eberle, Karen E.; Palmer, Glen E. (Estados Unidos: Antimicrobial Agents and Chemotherapy , 2015., 2019-10-02)

The purpose of this study was to characterize the effects of azole treatment upon the integrity of the Candida albicans vacuole and to determine whether, in turn, vacuolar trafficking influences azole susceptibility. ...

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ERG2 and ERG24 are required for normal vacuolar physiology as well as candida albicans pathogenicity in a murine model of disseminated but not vaginal candidiasis.
...
Luna Tapia, Arturo | 2019-10-01

Several important classes of antifungal agents, including the azoles, act by blocking ergosterol biosynthesis. It was recently reported that the azoles cause massive disruption of the fungal vacuole in the prevalent human pathogen Candida albicans. This is significant because normal vacuolar function is required to support C. albicans pathogenicity. This study examined the impact of the morpholine antifungals, which inhibit later steps of ergosterol biosynthesis, on C. albicans vacuolar integrity. It was found that overexpression of either the ERG2 or ERG24 gene, encoding C-8 sterol isomerase or C-14 sterol reductase, respectively, suppressed C. albicans sensitivity to the morpholines. In addition, both erg2 / and erg24 / mutants were hypersensitive to the morpholines. These data are consistent with the antifungal activity of the morpholines depending upon the simultaneous inhibition of both Erg2p and Erg24p. The vacuoles within both erg2 / and erg24 / C. albicans strains exhibited an aberrant morphology and accumulated large quantities of the weak base quinacrine, indicating enhanced vacuolar acidification compared with that of control strains. Both erg mutants exhibited significant defects in polarized hyphal growth and were avirulent in a mouse model of disseminated candidiasis. Surprisingly, in a mouse model of vaginal candidiasis, both mutants colonized mice at high levels and induced a pathogenic response similar to that with the controls. Thus, while targeting Erg2p or Erg24p alone could provide a potentially efficacious therapy for disseminated candidiasis, it may not be an effective strategy to treat vaginal infections. The potential value of drugs targeting these enzymes as adjunctive therapies is discussed.

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Three prevacuolar compartment Rab GTPases impact candida albicans hyphal growth.
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Johnston, Douglas A. | 2019-10-03

Disruption of vacuolar biogenesis in the pathogenic yeast Candida albicans causes profound defects in polarized hyphal growth. However, the precise vacuolar pathways involved in yeast-hypha differentiation have not been determined. Previously we focused on Vps21p, a Rab GTPase involved in directing vacuolar trafficking through the late endosomal prevacuolar compartment (PVC). Herein, we identify two additional Vps21p-related GTPases, Ypt52p and Ypt53p, that colocalize with Vps21p and can suppress the hyphal defects of the vps21 / mutant. Phenotypic analysis of gene deletion strains revealed that loss of both VPS21 and YPT52 causes synthetic defects in endocytic trafficking to the vacuole, as well as delivery of the virulence-associated vacuolar membrane protein Mlt1p from the Golgi compartment. Transcription of all three GTPase-encoding genes is increased under hyphal growth conditions, and overexpression of the transcription factor Ume6p is sufficient to increase the transcription of these genes. While only the vps21 / single mutant has hyphal growth defects, these were greatly exacerbated in a vps21 / ypt52 / double mutant. On the basis of relative expression levels and phenotypic analysis of gene deletion strains, Vps21p is the most important of the three GTPases, followed by Ypt52p, while Ypt53p has an only marginal impact on C. albicans physiology. Finally, disruption of a nonendosomal AP-3-dependent vacuolar trafficking pathway in the vps21 / ypt52 / mutant, further exacerbated the stress and hyphal growth defects. These findings underscore the importance of membrane trafficking through the PVC in sustaining the invasive hyphal growth form of C. albicans.

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Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals.
...
Luna Tapia, Arturo | 2019-10-02

The purpose of this study was to characterize the effects of azole treatment upon the integrity of the Candida albicans vacuole and to determine whether, in turn, vacuolar trafficking influences azole susceptibility. Profound fragmentation of the C. albicans vacuole can be observed as an early consequence of azole treatment, and it precedes significant growth inhibition. In addition, a C. albicans vps21/ mutant, blocked in membrane trafficking through the late endosomal prevacuolar compartment (PVC), is able to grow significantly more than the wild type in the presence of several azole antifungals under standard susceptibility testing conditions. F.

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Browsing by Author "Eberle, Karen E."

ERG2 and ERG24 are required for normal vacuolar physiology as well as candida albicans pathogenicity in a murine model of disseminated but not vaginal candidiasis.

Three prevacuolar compartment Rab GTPases impact candida albicans hyphal growth.

Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals.

Envíos recientes

ERG2 and ERG24 are required for normal vacuolar physiology as well as candida albicans pathogenicity in a murine model of disseminated but not vaginal candidiasis.

Three prevacuolar compartment Rab GTPases impact candida albicans hyphal growth.

Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals.

Browsing by Author "Eberle, Karen E."

ERG2 and ERG24 are required for normal vacuolar physiology as well as candida albicans pathogenicity in a murine model of disseminated but not vaginal candidiasis. ﻿

Three prevacuolar compartment Rab GTPases impact candida albicans hyphal growth. ﻿

Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals. ﻿

Envíos recientes

ERG2 and ERG24 are required for normal vacuolar physiology as well as candida albicans pathogenicity in a murine model of disseminated but not vaginal candidiasis.

Three prevacuolar compartment Rab GTPases impact candida albicans hyphal growth.

Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals.

ERG2 and ERG24 are required for normal vacuolar physiology as well as candida albicans pathogenicity in a murine model of disseminated but not vaginal candidiasis.

Three prevacuolar compartment Rab GTPases impact candida albicans hyphal growth.

Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals.