scholarly journals Molecular Mechanisms of Resistance to Antifungals in Candida albicans

2021 ◽  
Author(s):  
Estela Ruiz-Baca ◽  
Rosa Isela Arredondo-Sánchez ◽  
Karina Corral-Pérez ◽  
Angélica López-Rodríguez ◽  
Iván Meneses-Morales ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Molecular Mechanisms ◽  
Antifungal Agents ◽  
Point Mutations ◽  
Antifungal Resistance ◽  
Antifungal Drug ◽  
Antifungal Drug Resistance ◽  
Etiological Agents ◽  
Nosocomial Disease

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.

scholarly journals Effects of Azole Antifungal Drugs on the Transition from Yeast Cells to Hyphae in Susceptible and Resistant Isolates of the Pathogenic Yeast Candida albicans

1999 ◽  
Vol 43 (4) ◽  
pp. 763-768 ◽  
Author(s):  
Kien C. Ha ◽  
Theodore C. White
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Molecular Mechanisms ◽  
Opportunistic Infections ◽  
Antifungal Drugs ◽  
Yeast Cells ◽  
Pathogenic Yeast ◽  
Oral Infections ◽  
Antifungal Drug Resistance ◽  
Hyphal Formation

ABSTRACT Oral infections caused by the yeast Candida albicansare some 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 resistance, creating a major problem in the treatment of yeast infections in AIDS patients and other immunocompromised individuals. Several molecular mechanisms that contribute to drug resistance have been identified. InC. albicans, the ability to morphologically switch from yeast cells (blastospores) to filamentous forms (hyphae) is an important virulence factor which contributes to the dissemination ofCandida in host tissues and which promotes infection and invasion. A positive correlation between the level of antifungal drug resistance and the ability to form hyphae in the presence of azole drugs has been identified. Under hypha-inducing conditions in the presence of an azole drug, resistant clinical isolates form hyphae, while susceptible yeast isolates do not. This correlation is observed in a random sample from a population of susceptible and resistant isolates and is independent of the mechanisms of resistance.35S-methionine incorporation suggests that growth inhibition is not sufficient to explain the inhibition of hyphal formation, but it may contribute to this inhibition.

A systematic review on distribution and antifungal resistance pattern of Candida species in the Indian population

2021 ◽  
Author(s):  
Rashi Verma ◽  
Dibyabhaba Pradhan ◽  
Ziaul Hasan ◽  
Harpreet Singh ◽  
Arun Kumar Jain ◽  
...  
Keyword(s):  
Systematic Review ◽  
Drug Resistance ◽  
Candida Species ◽  
Indian Population ◽  
Antifungal Resistance ◽  
Antifungal Drug ◽  
Resistance Pattern ◽  
Indian States ◽  
Antifungal Drug Resistance ◽  
Resistance Patterns

Abstract The emergence of antifungal drug resistance in Candida species has led to increased morbidity and mortality in immunocompromised patients. Understanding species distribution and antifungal drug resistance patterns is an essential step for novel drug development. A systematic review was performed addressing this challenge in India with keywords inclusive of ‘Candida’, ‘Antifungal Drug Resistance’, ‘Candidemia’, ‘Candidiasis’ and ‘India’. A total of 106 studies (January 1978-March 2020) from 20 Indian states were included. Of over 11,429 isolates, Candida albicans was the major species accounting for 37.95% of total isolates followed by C. tropicalis (29.40%), C. glabrata (11.68%) and C. parapsilosis (8.36%). Rates of antifungal resistance were highest in non-albicans Candida (NAC) species - C. haemuloni (47.16%), C. krusei (28.99%), C. lipolytica (28.89%) and C. glabrata (20.69%). Approximately 10.34% isolates of C. albicans were observed to be drug-resistant. Candida species were frequently resistant to certain azoles (ketoconazole-22.2%, miconazole–22.1% and fluconazole–21.8%). In conclusion, the present systematic review illustrates the overall distribution and antifungal resistance pattern of Candida species among the Indian population that could be helpful in the future for the formation of treatment recommendations for the region but also elsewhere.

scholarly journals Transcriptional Analyses of Antifungal Drug Resistance in Candida albicans

2000 ◽  
Vol 44 (9) ◽  
pp. 2296-2303 ◽  
Author(s):  
Chris N. Lyons ◽  
Theodore C. White
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Efflux Pump ◽  
Carbon Sources ◽  
Antifungal Drug ◽  
Resistant Isolate ◽  
Mrna Levels ◽  
Pathogenic Yeast ◽  
Antifungal Drug Resistance ◽  
Logarithmic Growth

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.

scholarly journals An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses

2017 ◽  
Vol 13 (9) ◽  
pp. e1006655 ◽  
Author(s):  
Irene A. I. Hampe ◽  
Justin Friedman ◽  
Mira Edgerton ◽  
Joachim Morschhäuser
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Antifungal Drug ◽  
Host Defenses ◽  
Antifungal Drug Resistance

scholarly journals Molecular Mechanisms of Antifungal Drug Resistance in Candida Species

2018 ◽  
Author(s):  
Lakshmi Krishnasamy ◽  
Sharanya Krishnakumar ◽  
Govindasamy Kumaramanickavel ◽  
Chitralekha Saikumar
Keyword(s):  
Drug Resistance ◽  
Candida Species ◽  
Molecular Mechanisms ◽  
Antifungal Drug ◽  
Antifungal Drug Resistance

Antimycotic drugs and their mechanisms of resistance to Candida species

2021 ◽  
Vol 22 ◽  
Author(s):  
Sweety Dahiya ◽  
Namita Sharma ◽  
Aruna Punia ◽  
Pooja Choudhary ◽  
Prity Gulia ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Candida Species ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Treatment Strategies ◽  
Distinct Species ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Success Rates ◽  
Antifungal Drug Resistance

: Fungal infections have shown an upsurge in recent decades, mainly because of the increasing number of immunocompromised patients, and the occurrence of invasive candidiasis is found to be 7-15 folds greater than that of invasive aspergillosis. The genus Candida comprises of more than 150 distinct species; however, only a few of them are found to be pathogenic to humans. Mortality rates of Candida species are found to be around 45%, and the reasons for this intensified mortality are inefficient diagnostic techniques and unfitting initial treatment strategies. There are only a few antifungal drug classes that are employed for the remedy of invasive fungal infections, including azoles, polyenes, echinocandins, and pyrimidine analogs. During the last 2-3 decades, the usage of antifungal drugs has increased several folds, due to which the reports of escalating antifungal drug resistance have also been recorded. The resistance is mostly to the triazole-based compounds. Due to antifungal drug resistance, the success rates of treatment have been reduced and major changes have been observed in the frequency of fungal infections. In this review, we have summarized the major molecular mechanisms for the development of antifungal drug resistance.

scholarly journals Large-Scale Biochemical Profiling of the Candida albicans Biofilm Matrix: New Compositional, Structural, and Functional Insights

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Jose L. Lopez-Ribot
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Large Scale ◽  
Pathogenic Fungi ◽  
Antifungal Drug ◽  
Content Type ◽  
Antifungal Drug Resistance ◽  
Functional Aspects ◽  
Main Components ◽  
Biofilm Matrix

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.

Sign in / Sign up

Export Citation Format

Share Document