Fluconazole and Lipopeptide Surfactin Interplay During Candida albicans Plasma Membrane and Cell Wall Remodeling Increases Fungal Immune System Exposure DOI Creative Commons
Jakub Suchodolski, Daria Derkacz, Jakub Muraszko

et al.

Pharmaceutics, Journal Year: 2020, Volume and Issue: 12(4), P. 314 - 314

Published: April 1, 2020

Recognizing the β-glucan component of Candida albicans cell wall is a necessary step involved in host immune system recognition. Compounds that result exposed recognizable to could be valuable antifungal drugs. Antifungal development especially important because fungi are becoming increasingly drug resistant. This study demonstrates lipopeptide, surfactin, unmasks when C. cells lack ergosterol. observation also holds ergosterol depleted by fluconazole. Surfactin does not enhance effects local chitin accumulation presence Expression CHS3 gene, encoding gene product resulting 80% cellular chitin, downregulated. exposure fluconazole changes composition and structure fungal plasma membrane. At same time, altered remodeled way makes susceptible surfactin. In silico studies show surfactin can form complex with β-glucan. forms less stable which combination lowering synthesis, second anti-fungal mechanism action this lipopeptide.

Language: Английский

Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium DOI Creative Commons
Amir Arastehfar, Toni Gabaldón, Rocio Garcia‐Rubio

et al.

Antibiotics, Journal Year: 2020, Volume and Issue: 9(12), P. 877 - 877

Published: Dec. 8, 2020

The high clinical mortality and economic burden posed by invasive fungal infections (IFIs), along with significant agricultural crop loss caused various species, has resulted in the widespread use of antifungal agents. Selective drug pressure, attributes, host- drug-related factors have counteracted efficacy limited systemic drugs changed epidemiological landscape IFIs. Species belonging to Candida, Aspergillus, Cryptococcus, Pneumocystis are among pathogens showing notable rates resistance. Drug-resistant fungi from environment increasingly identified settings. Furthermore, we a understanding class-specific resistance mechanisms emerging Candida species. establishment stewardship programs both fields inclusion species identification, susceptibility testing, therapeutic monitoring practices clinic can minimize emergence drug-resistant fungi. New featuring promising profiles great promise treat setting. Mitigating tolerance, prelude resistance, also requires development effective fungal-specific adjuvants be used combination antifungals.

Language: Английский

Citations

212
Mutations in TAC1B : a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris DOI Creative Commons
Jeffrey M. Rybak, José F. Muñoz, Katherine S. Barker

et al.

mBio, Journal Year: 2020, Volume and Issue: 11(3)

Published: May 11, 2020

Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and commonly resistant antifungals. While the vast majority clinical C. isolates are highly fluconazole, essential part available antifungal arsenal, very little about mechanisms contributing resistance. In this work, we show that mutations in transcription factor TAC1B significantly contribute fluconazole These studies demonstrated can arise rapidly vitro upon exposure a multitude resistance-associated present among fluconazole-resistant from collection appear specific subset lineages or clades. Thus, identification novel genetic determinant resistance adds understanding .

Language: Английский

Citations

146
Protein–protein interaction prediction with deep learning: A comprehensive review DOI Creative Commons
Farzan Soleymani, Eric Paquet, Herna L. Viktor

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2022, Volume and Issue: 20, P. 5316 - 5341

Published: Jan. 1, 2022

Most proteins perform their biological function by interacting with themselves or other molecules. Thus, one may obtain insights into protein functions, disease prevalence, and therapy development identifying protein–protein interactions (PPI). However, finding the non-interacting pairs through experimental approaches is labour-intensive time-consuming, owing to variety of proteins. Hence, interaction protein–ligand binding problems have drawn attention in fields bioinformatics computer-aided drug discovery. Deep learning methods paved way for scientists predict 3-D structure from genomes, functions attributes a protein, modify design new provide desired functions. This review focuses on recent deep applied including predicting sites, binding, design.

Language: Английский

Citations

102
Fungal Drug Response and Antimicrobial Resistance DOI Creative Commons

Paloma Osset-Trénor,

Amparo Pascual‐Ahuir, Markus Proft

et al.

Journal of Fungi, Journal Year: 2023, Volume and Issue: 9(5), P. 565 - 565

Published: May 12, 2023

Antifungal resistance is a growing concern as it poses significant threat to public health. Fungal infections are cause of morbidity and mortality, especially in immunocompromised individuals. The limited number antifungal agents the emergence have led critical need understand mechanisms drug resistance. This review provides an overview importance resistance, classes agents, their mode action. It highlights molecular including alterations modification, activation, availability. In addition, discusses response drugs via regulation multidrug efflux systems drug–target interactions. We emphasize understanding develop effective strategies combat highlight for continued research identify new targets development explore alternative therapeutic options overcome Overall, its will be indispensable field clinical management fungal infections.

Language: Английский

Citations

50
Candidiasis: From cutaneous to systemic, new perspectives of potential targets and therapeutic strategies DOI
Hui Lu, Ting Hong, Yuanying Jiang

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 199, P. 114960 - 114960

Published: June 10, 2023

Language: Английский

Citations

46
Mechanisms of Azole Potentiation: Insights from Drug Repurposing Approaches DOI
Juan Xiong, Hui Lu, Yuanying Jiang

et al.

ACS Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

The emergence of azole resistance and tolerance in pathogenic fungi has emerged as a significant public health concern, emphasizing the urgency for innovative strategies to bolster efficacy azole-based treatments. Drug repurposing stands promising practical avenue advancing antifungal therapy, with potential swift clinical translation. This review offers comprehensive overview synergistic agents uncovered through drug strategies, alongside an in-depth exploration mechanisms by which these augment potency. Drawing from mechanisms, we delineate aimed at enhancing effectiveness, such inhibiting efflux pumps elevate concentrations within fungal cells, intensifying ergosterol synthesis inhibition, mitigating cell azoles, disrupting biological processes extending beyond synthesis. is beneficial development potentiators, it meticulously examines instances provides nuanced discussions on underlying progression potentiators strategies.

Language: Английский

Citations

2
First Report of Candidemia Clonal Outbreak Caused by Emerging Fluconazole-Resistant Candida parapsilosis Isolates Harboring Y132F and/or Y132F+K143R in Turkey DOI Open Access
Amir Arastehfar, Farnaz Daneshnia, Süleyha Hilmioğlu Polat

et al.

Antimicrobial Agents and Chemotherapy, Journal Year: 2020, Volume and Issue: 64(10)

Published: July 16, 2020

Clonal outbreaks of fluconazole-resistant (FLZR) Candida parapsilosis isolates have been reported in several countries. Despite its being the second leading cause candidemia, azole resistance mechanisms and clonal expansion FLZR C. blood not Turkey. In this study, we consecutively collected (n = 225) from fifth largest hospital Turkey (2007 to 2019), assessed their susceptibility pattern using CLSI M27-A3/S4, sequenced ERG11 for all MRR1, TAC1, UPC2 a selected number isolates. The typing resolution two widely used techniques, amplified fragment length polymorphism (AFLP) microsatellite (MST), biofilm production with without Y132F were compared. Approximately 27% (60/225), among which 90% (54/60) harbored known mutations Erg11, including (24/60) Y132F+K143R (19/60). Several specific found AFLP grouped into clusters, while MST revealed clusters. majority Y132F/Y132F+K143R significantly expanded throughout 2007 2019 neonatal wards. carrying associated higher mortality less than other Collectively, documented first outbreak exclusively establishes basis future studies, will potentially broaden our knowledge should be preferred method analysis scenarios.

Language: Английский

Citations

90
Genomic Diversity across Candida auris Clinical Isolates Shapes Rapid Development of Antifungal Resistance In Vitro and In Vivo DOI Creative Commons
Laura S. Burrack, Robert T. Todd, Natthapon Soisangwan

et al.

mBio, Journal Year: 2022, Volume and Issue: 13(4)

Published: July 5, 2022

Drug resistant Candida auris infections are recognized by the CDC as an urgent threat. Here, we obtained and characterized a set of clinical isolates C. including multiple from same patient.

Language: Английский

Citations

48
Emergence and circulation of azole-resistant C. albicans, C. auris and C. parapsilosis bloodstream isolates carrying Y132F, K143R or T220L Erg11p substitutions in Colombia DOI Creative Commons
Andrés Ceballos-Garzón,

Ana Peñuela,

Sandra Valderrama

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: March 21, 2023

Over a four-year period, 123 Candida bloodstream isolates were collected at quaternary care hospital. The identified by MALDI-TOF MS and their fluconazole (FLC) susceptibility patterns assessed according to CLSI guidelines. Subsequently, sequencing of ERG11, TAC1 or MRR1, efflux pump activity performed for resistant isolates.

Language: Английский

Citations

24
Upc2-mediated mechanisms of azole resistance in Candida auris DOI Creative Commons
Jizhou Li,

Lola Aubry,

Danielle Brandalise

et al.

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: 12(2)

Published: Jan. 11, 2024

is an emerging yeast pathogen of major concern because its ability to cause hospital outbreaks invasive candidiasis and develop resistance antifungal drugs. A majority

Language: Английский

Citations

12