N‐acetylglucosamine transporter, Ngt1, undergoes sugar‐responsive endosomal trafficking in Candida albicans

2021 ◽  
Author(s):  
Hanumantha Rao Kongara ◽  
Kasturi Roy ◽  
Soumita Paul ◽  
Swagata Ghosh
Keyword(s):  
Candida Albicans ◽  
Endosomal Trafficking

scholarly journals Endosomal and AP-3-Dependent Vacuolar Trafficking Routes Make Additive Contributions to Candida albicans Hyphal Growth and Pathogenesis

2010 ◽  
Vol 9 (11) ◽  
pp. 1755-1765 ◽  
Author(s):  
Glen E. Palmer
Keyword(s):  
Candida Albicans ◽  
Double Mutant ◽  
Kidney Tissue ◽  
Hyphal Growth ◽  
Endosomal Trafficking ◽  
Transcriptional Responses ◽  
Transport Pathways ◽  
Content Type ◽  
Vacuolar Protein ◽  
Vacuolar Trafficking

ABSTRACT Candida albicans mutants deficient in vacuolar biogenesis are defective in polarized hyphal growth and virulence. However, the specific vacuolar trafficking routes required for hyphal growth and virulence are unknown. In Saccharomyces cerevisiae, two trafficking routes deliver material from the Golgi apparatus to the vacuole. One occurs via the late endosome and is dependent upon Vps21p, while the second bypasses the endosome and requires the AP-3 complex, including Aps3p. To determine the significance of these pathways in C. albicans hyphal growth and virulence, aps3Δ/Δ, vps21Δ/Δ, and aps3Δ/Δ vps21Δ/Δ mutant strains were constructed. Analysis of vacuolar morphology and localization of the vacuolar protein Mlt1p suggests that C. albicans Aps3p and Vps21p mediate two distinct transport pathways. The vps21Δ/Δ mutant has a minor reduction in hyphal elongation, while the aps3Δ/Δ mutant has no defect in hyphal growth. Interestingly, the aps3Δ/Δ vps21Δ/Δ double mutant has dramatically reduced hyphal growth. Overexpression of the Ume6p transcriptional activator resulted in constitutive hyphal growth of wild-type, aps3Δ/Δ, and vps21Δ/Δ strains and formation of highly vacuolated subapical compartments. Thus, Ume6p-dependent transcriptional responses are sufficient to induce subapical vacuolation. However, the aps3Δ/Δ vps21Δ/Δ mutant formed mainly pseudohyphae that lacked vacuolated compartments. The aps3Δ/Δ strain was virulent in a mouse model of disseminated infection; the vps21Δ/Δ mutant failed to kill mice but persisted within kidney tissue, while the double mutant was avirulent and cleared from the kidneys. These results suggest that while the AP-3 pathway alone has little impact on hyphal growth or virulence, it is much more significant when endosomal trafficking is disrupted.

scholarly journals Trafficking through the Late Endosome Significantly Impacts Candida albicans Tolerance of the Azole Antifungals

2015 ◽  
Vol 59 (4) ◽  
pp. 2410-2420 ◽  
Author(s):  
Arturo Luna-Tapia ◽  
Morgan E. Kerns ◽  
Karen E. Eberle ◽  
Branko S. Jursic ◽  
Glen E. Palmer
Keyword(s):  
Candida Albicans ◽  
Membrane Trafficking ◽  
Ergosterol Biosynthesis ◽  
Endosomal Trafficking ◽  
Membrane Function ◽  
Content Type ◽  
Azole Antifungals ◽  
Trafficking Defects ◽  
Lanosterol Demethylase ◽  
Cellular Compartments

ABSTRACTThe azole antifungals block ergosterol biosynthesis by inhibiting lanosterol demethylase (Erg11p). The resulting depletion of cellular ergosterol and the accumulation of “toxic” sterol intermediates are both thought to compromise plasma membrane function. However, the effects of ergosterol depletion upon the function of intracellular membranes and organelles are not well described. The purpose of this study was to characterize the effects of azole treatment upon the integrity of theCandida albicansvacuole and to determine whether, in turn, vacuolar trafficking influences azole susceptibility. Profound fragmentation of theC. albicansvacuole can be observed as an early consequence of azole treatment, and it precedes significant growth inhibition. In addition, aC. albicansvps21Δ/Δ 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. Furthermore, thevps21Δ/Δ mutant is able to grow despite the depletion of cellular ergosterol. This phenotype resembles an exaggerated form of “trailing growth” that has been described for some clinical isolates. In contrast, thevps21Δ/Δ mutant is hypersensitive to drugs that block alternate steps in ergosterol biosynthesis. On the basis of these results, we propose that endosomal trafficking defects may lead to the cellular “redistribution” of the sterol intermediates that accumulate following inhibition of ergosterol biosynthesis. Furthermore, the destination of these intermediates, or the precise cellular compartments in which they accumulate, may be an important determinant of their toxicity and thus ultimately antifungal efficacy.

scholarly journals An Azole-Tolerant Endosomal Trafficking Mutant of Candida albicans Is Susceptible to Azole Treatment in a Mouse Model of Vaginal Candidiasis

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Brian M. Peters ◽  
Arturo Luna-Tapia ◽  
Hélène Tournu ◽  
Jeffrey M. Rybak ◽  
P. David Rogers ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mouse Model ◽  
Vaginal Candidiasis ◽  
Azole Resistance ◽  
Endosomal Trafficking ◽  
Wild Type ◽  
Content Type ◽  
Azole Antifungals

ABSTRACT We recently reported that a Candida albicans endosomal trafficking mutant continues to grow after treatment with the azole antifungals. Herein, we report that the vps21Δ/Δ mutant does not have a survival advantage over wild-type isolates after fluconazole treatment in a mouse model of vaginal candidiasis. Furthermore, loss of VPS21 does not synergize with established mechanisms of azole resistance, such as overexpression of efflux pumps or of Erg11p, the target enzyme of the azoles. In summary, although loss of VPS21 function enhances C. albicans survival after azole treatment in vitro, it does not seem to affect azole susceptibility in vivo.

Enhanced IgE response to Candida albicans in postoperative invasive candidiasis

1996 ◽  
Vol 26 (4) ◽  
pp. 452-460 ◽  
Author(s):  
J. SAVOLAINEN ◽  
A. RANTALA ◽  
M. NERMES ◽  
L. LEHTONEN ◽  
M. VIANDER
Keyword(s):  
Candida Albicans ◽  
Invasive Candidiasis ◽  
Ige Response

Existence of Candida albicans and microorganisms in denture stomatitis patients

1997 ◽  
Vol 24 (10) ◽  
pp. 788-790 ◽  
Author(s):  
Y. KULAK ◽  
A. ARIKAN ◽  
E. KAZAZOGLU
Keyword(s):  
Candida Albicans ◽  
Denture Stomatitis
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