scholarly journals The lipid flippase subunit Cdc50 is required for antifungal drug resistance, endocytosis, hyphal development and virulence in Candida albicans

2019 ◽  
Vol 19 (3) ◽  
Author(s):  
Dayong Xu ◽  
Xing Zhang ◽  
Biao Zhang ◽  
Xin Zeng ◽  
Hongchen Mao ◽  
...  
2000 ◽  
Vol 44 (9) ◽  
pp. 2296-2303 ◽  
Author(s):  
Chris N. Lyons ◽  
Theodore C. White

ABSTRACT Oral infections with the pathogenic yeast Candida albicans are one of the most frequent and earliest opportunistic infections in human immunodeficiency virus-infected patients. The widespread use of azole antifungal drugs has led to the development of drug-resistant isolates. Several molecular mechanisms that contribute to drug resistance have been identified, including increased mRNA levels for two types of efflux pump genes: the ATP binding cassette transporter CDRs (CDR1 and CDR2) and the major facilitator MDR1. Using Northern blot analyses, the expression patterns of these genes have been determined during logarithmic and stationary phases of cell growth and during growth in different carbon sources in a set of matched susceptible and fluconazole-resistant isolates that have been characterized previously.MDR1, CDR1, and CDR2 are expressed early during logarithmic growth, CDR4 is expressed late during logarithmic growth, and CDR1 is preferentially expressed in stationary-phase cells. There is a small decrease in expression of these genes when the cells are grown in carbon sources other than glucose. While increased mRNA levels of efflux pump genes are commonly associated with azole resistance, the causes of increased mRNA levels have not yet been resolved. Southern blot analysis demonstrates that the increased mRNA levels in these isolates are not the result of gene amplification. Nuclear run-on assays show thatMDR1 and CDR mRNAs are transcriptionally overexpressed in the resistant isolate, suggesting that the antifungal drug resistance in this series is associated with the promoter andtrans-acting factors of the CDR1,CDR2, and MDR1 genes.


2017 ◽  
Vol 13 (9) ◽  
pp. e1006655 ◽  
Author(s):  
Irene A. I. Hampe ◽  
Justin Friedman ◽  
Mira Edgerton ◽  
Joachim Morschhäuser

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Jose L. Lopez-Ribot

ABSTRACTAmong pathogenic fungi,Candida albicansis most frequently associated with biofilm formation, a lifestyle that is entirely different from the planktonic state. One of the distinguishing features of these biofilms is the presence of extracellular material, commonly referred to as the “biofilm matrix.” The fungal biofilm matrix embeds sessile cells within these communities and plays important structural and physiological functions, including antifungal drug resistance with important clinical repercussions. This matrix is mostly self-produced by the fungal cells themselves and is composed of different types of biopolymers. InC. albicans, the main components of the biofilm matrix are carbohydrates, proteins, lipids, and DNA, but many of them remain unidentified and/or poorly characterized. In their recent article, Zarnowski et al. [mBio 5(4):e01333-14, 2014, doi:10.1128/mBio.01333-14] used a variety of biochemical and state-of-the-art “omic” approaches (glycomics, proteomics, and lipidomics) to identify and characterize unique biopolymers present in theC. albicansbiofilm matrix. Besides generating a true “encyclopedic” catalog of individual moieties from each of the different macromolecular categories, results also provide important insights into structural and functional aspects of the fungal biofilm matrix, particularly the interaction between different components and the contribution of multiple matrix constituents to biofilm antifungal drug resistance.


2021 ◽  
Author(s):  
Estela Ruiz-Baca ◽  
Rosa Isela Arredondo-Sánchez ◽  
Karina Corral-Pérez ◽  
Angélica López-Rodríguez ◽  
Iván Meneses-Morales ◽  
...  

Invasive Candidiasis (IC) presents a global mortality rate greater than 40%, occupying the fourth place worldwide as the most frequent opportunistic nosocomial disease. Although the genus Candida consists of around 200 species, only 20 are reported as etiological agents of IC, being Candida albicans the most frequent causal agent. Even when there is a broad range of antifungals drugs for Candida infections, azoles, polyenes, and echinocandins are considered among the most effective treatment. However, there is some incidence for antifungal resistance among some Candida strains, limiting treatment options. Several molecular mechanisms with antifungal agents have been reported for C. albicans where insertions, deletions, and point mutations in genes codifying target proteins are frequently related to the antifungal drug resistance. Furthermore, gene overexpression is also frequently associated to antifungal resistance as well as an increase in the activity of proteins that reduce oxidative damage. This chapter summarizes the main molecular mechanisms to C. albicans antifungal drug resistance, besides offering an overview of new antifungal agents and new antifungal targets to combat fungal infections.


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