Insights for Combating Multidrug-Resistant Candida: A New Frontier in Antifungal Therapy

Fungal infections caused by Candida species pose a growing threat to global health, particularly in immunocompromised and critically ill patients. The rise of multidrug-resistant Candida spp. has undermined the effectiveness of existing antifungal therapies, leading to higher morbidity, mortality, and healthcare costs. Beyond simple treatment failure, resistance is closely linked to changes in virulence traits and infection pathogenesis, including altered host–pathogen interactions, immune evasion, tissue invasion, and persistence in clinical settings. A comprehensive understanding of how antifungal resistance reshapes Candida spp. biology at the cellular, molecular, and host–pathogen interaction levels is critical for the development of rational and durable therapeutic strategies aligned with current clinical and epidemiological realities.This article collection focuses on generating mechanistic and translational insights into multidrug-resistant Candida spp., addressing target assessment, antifungal drug discovery, and therapeutic development. Contributions should elucidate how antifungal resistance reshapes virulence, pathogenic traits, and treatment outcomes, and how these resistance-associated insights can be leveraged to identify and validate novel drug targets, optimize lead compounds, and design innovative antifungal strategies. We welcome studies spanning early-stage target identification and validation, mechanistic characterization of resistance–virulence interplay, preclinical development of small molecules or biologics, and innovative approaches to combination therapy or host-directed interventions. By integrating experimental and translational perspectives, this collection aims to advance the pipeline of next-generation antifungals against Candida spp. and improve management of invasive and mucosal candidiasis in the era of escalating resistance.To explore the impacts and innovative solutions to multidrug-resistant Candida spp., the following, non-exhaustive themes will be addressed.• Original research on how antifungal resistance reshapes Candida spp. virulence factors (e.g., adhesion, invasion, biofilm formation, secreted enzymes) and infection outcomes, providing insights to inform novel therapeutic strategies.• Studies identifying and validating novel antifungal targets in Candida spp. (e.g., enzymes, signaling pathways, cell wall or membrane components) using genetic, biochemical, pharmacological, and omics-based approaches.• Drug discovery reports describing hit identification, hit-to-lead optimization, and structure–activity relationship studies for new anti-Candida compounds active against resistant isolates.• Mechanistic investigations into how resistance mechanisms (e.g., target modification, efflux, stress responses) reshape Candida spp. pathogenesis and host–pathogen interactions.• Preclinical evaluation of new antifungal candidates (small molecules, peptides, antibodies, or biologics) against resistant Candida spp. in relevant in vitro and in vivo infection models.• Studies on combination therapies (antifungal–antifungal or antifungal–non-antifungal) designed to overcome resistance, reduce virulence, or prevent the emergence of resistant Candida spp. populations.• Research on host-directed or immune-modulating therapeutic strategies that mitigate disease severity or enhance clearance of drug-resistant Candida spp.• Investigations of biofilm-associated resistance and tolerance in Candida spp. that explore molecular pathways linking biofilm biology to virulence, with relevance for the development of novel antifungal therapies.• Pharmacokinetic/pharmacodynamic (PK/PD) and dose-optimization studies for existing or novel antifungals against resistant Candida spp..• Clinical or translational studies correlating resistance profiles with virulence traits, disease severity, treatment response, and patient outcomes to inform target prioritization and therapeutic design.• Reviews or mini-reviews synthesizing current knowledge on antifungal target assessment, drug development pipelines, and the resistance–virulence relationship in Candida spp.• Methodological or technological papers describing innovative platforms (e.g., phenotypic screening, target-based assays, high-content infection models) that accelerate target discovery and antifungal development for drug-resistant Candida spp. Topic editors: Estela Ruiz-Baca, Lívia Gurgel do Amaral Valente Sá, Sueli Fumie Yamada-Ogatta Source: https://www.frontiersin.org/research-topics/78595/insights-for-combating-multidrug-resistant-candida-a-new-frontier-in-antifungal-therapy