Drugs Commonly Used in Fungal Infection Risk Conditions Promote Drug Tolerance or Resistance in Candida albicans DOI Open Access
Martin Obermeier, Margy Alejandra Esparza Mora,

Oliver Heese

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 9, 2024

Abstract Background Fungal infections are an increasing concern, particularly among immunocompromised patients and those with comorbidities who require multiple medications. However, the effects of drugs targeting human pathways on fungal cells, whether they influence antifungal drug responses, poorly understood. Methods We systematically analyzed clinical guidelines to shortlist non-antifungal commonly used in conditions that increase likelihood infections. Focusing most prevalent pathogen, we then tested how these affected response Candida albicans two antifungals, fluconazole anidulafungin. Drug interactions identified were further assessed using checkerboard disk diffusion assays. Finally, treatment efficacy combination negatively interacting was evaluated vivo Galleria mellonella model disseminated C. infection. Findings Out 119 frequently co-administered antifungals 40 associated a high risk infections, 34 compounds , reducing or antagonising efficacy, several through resistance tolerance. Notably, combinations carvedilol loperamide promoted both cultures . Interpretation Our findings suggest medications taken by at regularly act pathogens can affect effectiveness antifungals. propose acting may be underestimated factor contributing evolution tolerance resistance.

Language: Английский

Focus on fungi DOI
Iliyan D. Iliev, Gordon D. Brown, Petra Bächer

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5121 - 5127

Published: Sept. 1, 2024

Language: Английский

Citations

17
Drug tolerance and persistence in bacteria, fungi and cancer cells: Role of non-genetic heterogeneity DOI Creative Commons
Imane El Meouche, Paras Jain, Mohit Kumar Jolly

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 49, P. 102069 - 102069

Published: Aug. 8, 2024

Language: Английский

Citations

5
Environmental microbiome, human fungal pathogens, and antimicrobial resistance DOI
Zhenzhen Yan, Hang‐Wei Hu, Chao Xiong

et al.

Trends in Microbiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

4
Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata DOI Creative Commons

Taiga Miyazaki,

Shintaro Shimamura,

Yohsuke Nagayoshi

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 25, 2025

Multidrug resistance in the pathogenic fungus Candida glabrata is a growing global threat. Here, we study mechanisms of multidrug this pathogen. Exposure C. cells to micafungin (an echinocandin) leads isolation mutant exhibiting echinocandin and azole antifungals. The drug-resistant phenotype due non-synonymous mutation (R70H) gene IPI1, which involved pre-rRNA processing. Azole ipi1R70H depends on Pdr1 transcription factor, regulates expression transporters. Ipi1 protein physically interacts with ribosome-related chaperones Ssb Ssz1, both bind Pdr1. Ipi1-Ssb/Ssz1 complex inhibits Pdr1-mediated glabrata, contrast Saccharomyces cerevisiae where Ssz1 acts as positive regulator Furthermore, exposure reduces metabolic activity cell proliferation mutant, may contribute tolerance. authors show that processing, pathogen by affecting interactions between two factor transporter expression.

Language: Английский

Citations

0
Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance DOI Creative Commons

Yanyu Su,

Yi Li,

Qiaolian Yi

et al.

Journal of Fungi, Journal Year: 2025, Volume and Issue: 11(2), P. 143 - 143

Published: Feb. 13, 2025

Antifungal resistance poses a critical global health threat, particularly in immuno-compromised patients. Beyond the traditional mechanisms rooted heritable and stable mutations, distinct phenomenon known as heteroresistance has been identified, wherein minority of resistant fungal cells coexist within predominantly susceptible population. Heteroresistance may be induced by pharmacological factors or non-pharmacological agents. The reversible nature it presents significant clinical challenges, can lead to undetected during standard susceptibility testing. As allows pathogens survive antifungal treatment, this adaptive strategy often leads treatment failure recurring infection. Though extensively studied bacteria, limited research explored its occurrence fungi. This review summarizes current findings on mechanisms, highlighting implications pressing need for deeper mechanism insights. We aim bring together latest advances field heteroresistance, summarizing detail characteristics, inducing factors, molecular significance, describing similarities differences between tolerance persistence. Further is needed understand develop more effective therapies combat infections.

Language: Английский

Citations

0
Peppermint Essential Oil For Controlling Aspergillus flavus and Analysis of its Antifungal Action Mode DOI
Yanjie Yi, Rumeng Liu,

Zijun Shang

et al.

Current Microbiology, Journal Year: 2025, Volume and Issue: 82(4)

Published: Feb. 18, 2025

Language: Английский

Citations

0
Induction of Antifungal Tolerance Reveals Genetic and Phenotypic Changes in Candida glabrata DOI Creative Commons

Christy Chedraoui,

Nour Fattouh,

Setrida El Hachem

et al.

Journal of Fungi, Journal Year: 2025, Volume and Issue: 11(4), P. 284 - 284

Published: April 4, 2025

Candida glabrata is an opportunistic, pathogenic fungus that increasingly isolated from hospitalized patients. The incidence of drug tolerance, heteroresistance, and resistance on the rise due to overuse antifungal drugs. aim this study was expose a sensitive C. strain sequentially increasing concentrations two drugs, fluconazole, azole targets ergosterol biosynthesis, or caspofungin, echinocandin cell wall glucan synthesis. Analysis drug-exposed isolates showed development chromosomal abnormalities, decreased adhesion, attenuated virulence, increase in efflux pump activity. Furthermore, whole genome sequencing all exposed different fluconazole caspofungin performed determine mutations key genes could correlate with observed phenotypes. Mutations were found implicated such as AWP, PWP, EPA family genes. Isolates higher displayed more than those at lower concentrations.

Language: Английский

Citations

0
Vaginal mycobiome characteristics and therapeutic strategies in vulvovaginal candidiasis (VVC): differentiating pathogenic species and microecological features for stratified treatment DOI

Zimo Liu,

Hua Yang,

Roujie Huang

et al.

Clinical Microbiology Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

SUMMARY Vulvovaginal candidiasis (VVC) is a prevalent global health burden, particularly among reproductive-aged women. Recurrent VVC affects significant proportion of this population, presenting therapeutic challenges. The predominant pathogen, Candida albicans , opportunistically transitions from commensal organism to pathogen when microenvironmental conditions become dysregulated. Recently, non- species have gained attention for their reduced antifungal susceptibility and recurrence tendencies. Diagnosis constrained by the limitations conventional microbiological techniques, while emerging molecular assays offer enhanced detection yet lack established thresholds differentiate between pathogenic states. Increasing resistance issues are encountered traditional azole-based antifungals, necessitating innovative approaches that integrate microbiota modulation precision medicine. Therefore, review aims systematically explore diversity, drug mechanisms, biofilm effects species. Vaginal (VMB) alterations associated with were also examined, focusing on interaction Lactobacillus spp. fungi, emphasizing role microbial dysbiosis in disease progression. Finally, potential summarized, particular focus use probiotics modulate VMB composition restore healthy ecosystem as promising treatment strategy. This addresses adopts microbiota-centric approach, proposing comprehensive framework personalized management reduce improve patient outcomes.

Language: Английский

Citations

0
Miconazole induces aneuploidy-mediated tolerance in Candida albicans that is dependent on Hsp90 and calcineurin DOI Creative Commons
Liangsheng Guo, Lijun Zheng, Yubo Dong

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: June 25, 2024

Antifungal resistance and antifungal tolerance are two distinct terms that describe different cellular responses to drugs. describes the ability of a fungus grow above minimal inhibitory concentration (MIC) drug. drug susceptible strains slowly at concentrations. Recent studies indicate have evolutionary trajectories. Superficial candidiasis bothers millions people yearly. Miconazole has been used for topical treatment yeast infections over 40 years. Yet, fungal miconazole remains relatively low. Here we found clinical isolates Candida albicans had profile miconazole, was modulated by physiological factors including temperature medium composition. Exposure non-tolerant with genetic backgrounds mainly induced development tolerance, not resistance, due whole chromosomal or segmental amplification chromosome R. The efflux gene CDR1 required maintenance in wild type but gain aneuploidy-mediated tolerance. Heat shock protein Hsp90 calcineurin were essential as well Our study indicates is predominant mechanism rapid adaptation C. , relevance deserves further investigations.

Language: Английский

Citations

2
Ketoconazole induces reversible antifungal drug tolerance mediated by trisomy of chromosome R in Candida albicans DOI Creative Commons
Lijun Zheng, Yi Xu, Chen Wang

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: July 30, 2024

Background The emergence of tolerance to antifungal agents in Candida albicans complicates the treatment fungal infections. Understanding mechanisms underlying this is crucial for developing effective therapeutic strategies. Objective This study aims elucidate genetic and molecular basis ketoconazole C. , focusing on roles chromosomal aneuploidy, Hsp90, calcineurin. Methods wild-type strain SC5314 was exposed increasing concentrations (0.015–32 μg/mL) select tolerant adaptors. Disk diffusion spot assays were used assess tolerance. Whole-genome sequencing identified changes Hsp90 calcineurin maintaining investigated using specific inhibitors knockout strains. Results Adaptors exhibited up 16 μg/mL, a significant increase from parent strain’s inhibition at 0.015 μg/mL. All adaptors showed amplification chromosome R, with 29 having trisomy one tetrasomy. aneuploidy unstable, reverting euploidy losing drug-free conditions. Both essential Inhibition these proteins resulted loss efflux gene CDR1 not required development Chromosome R tetrasomy induce cross-tolerance other azole agents, including clotrimazole miconazole, but classes, such as echinocandins pyrimidines, exemplified by caspofungin 5-flucytosine. Conclusion Ketoconazole mediated specifically amplification, requires These findings highlight potential targets intervention combat improve outcomes.

Language: Английский

Citations

1