Emergence of Triazole-Resistant Cryptococcus neoformans after Exposure to Environmentally Relevant Concentrations of Difenoconazole in Liquid Medium and Soil

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

The rapid global emergence and spread of resistance to clinical triazoles in Cryptococcus neoformans have been associated with the use agricultural triazole fungicides. However, there is no direct evidence currently linking triazole-resistant C. (TRCN) strains application fungicides soil. This study investigated whether could be induced by difenoconazole, an fungicide, liquid medium Our findings reveal that environmentally relevant concentrations difenoconazole can drive cross-resistance through upregulation ERG11 efflux pump genes (AFR1, AFR3, MDR1). Notably, prevalence TRCN soil correlates residual levels, significantly more isolates observed at two- five-fold recommended dose than standard dose. These results provide highlight importance applying or below dosage mitigate development environments. addresses a critical gap understanding environmental drivers underscores need for responsible fungicide prevent resistant pathogens.

Language: Английский

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Rise and fall of Caspofungin: the current status of Caspofungin as a treatment for Cryptococcus neoformans infection

Future Microbiology, Journal Year: 2024, Volume and Issue: 19(7), P. 621 - 630

Published: March 18, 2024

Antifungal infections are becoming a major concern to human health due antimicrobial resistance. Echinocandins have been promising agents against resistant fungal infections, primarily caspofungin, which has more effective mechanism of action than azoles and polyenes. However, fungi such as Cryptococcus neoformans appear be inheritably these drugs, is concerning the high clinical importance C. neoformans. In this review, we review history treatments used treat antifungals over years, focusing on while highlighting problem possible explanations for its inherent

Language: Английский

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Temporal trends in antifungal susceptibility of Cryptococcus neoformans isolates from a reference laboratory in the United States, 2011–2021

Mycoses, Journal Year: 2024, Volume and Issue: 67(1)

Published: Jan. 1, 2024

Abstract Background There are no established clinical breakpoints for antifungal agents against Cryptococcus species; however, epidemiological cut‐off values can help distinguish wild‐type (WT) isolates without any acquired resistance from non‐WT strains, which may harbour mechanisms. Patients/Methods We describe the trends of MICs and percentages WT C. neoformans species complex (CNSC) processed in our reference laboratory November 2011 to June 2021. were only nine 2011, thus, we included them year 2012 data analysis. Clinical is also described when available. Results identified 632 CNSC, majority collected blood ( n = 301), cerebrospinal fluid 230), respiratory 71) sources. The overall percentage amphotericin B (AMB), 5‐flucytosine, fluconazole was 77%, 98%, 91%, respectively. noticed a statistically significant change AMB over years, with 98% being compared 79% 2021 p < .01). A similar not observed other agents. available 36 patients, primarily non‐HIV immunocompromised patients disseminated cryptococcosis. differences characteristics outcomes between (58.3%) versus (41.7%) isolates, but higher mortality infected an CNSC isolate. Conclusions increase past decade. implications this finding warrant further evaluation larger studies.

Language: Английский

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Fungal Infections, Treatment and Antifungal Resistance: The Sub-Saharan African Context

Therapeutic Advances in Infectious Disease, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 1, 2024

Fungal pathogens cause a wide range of infections in humans, from superficial to disfiguring, allergic syndromes, and life-threatening invasive infections, affecting over billion individuals globally. With an estimated 1.5 million deaths annually attributable them, fungal are major mortality especially people with underlying immunosuppression. The continuous increase the population at risk sub-Saharan Africa, such as HIV patients, tuberculosis intensive care patients haematological malignancies, transplant (haematopoietic stem cell organ) recipients growing global threat multidrug-resistant strains, raise need for appreciation region’s perspective on antifungal usage resistance. In addition, unavailability recently introduced novel drugs Africa further calls regular evaluation resistance agents these settings. This is critical ensuring appropriate optimal use limited available arsenal minimise review, therefore, elaborates multifaceted nature market provides insights into prevalence Africa.

Language: Английский

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Reduced Susceptibility to Azoles in Cryptococcus gattii Correlates with the Substitution R258L in a Substrate Recognition Site of the Lanosterol 14-α-Demethylase

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 11(4)

Published: June 21, 2023

Cryptococcus neoformans and gattii cause cryptococcosis, a life-threatening fungal infection affecting mostly immunocompromised patients. In fact, cryptococcal meningitis accounts for about 19% of AIDS-related deaths in the world. Because long-term azole therapies to treat this mycosis, resistance fluconazole leading treatment failure poor prognosis has long been reported both species. Among mechanisms implicated azoles, mutations ERG11 gene, encoding target enzyme lanosterol 14-α-demethylase, have described. This study aimed establish amino acid composition Colombian clinical isolates C. correlate any possible substitution with vitro susceptibility profile fluconazole, voriconazole, itraconazole. Antifungal testing results showed that are less susceptible azoles than isolates, which could differences structure each addition, isolate high MICs (64 μg/mL) voriconazole (1 μg/mL), G973T mutation resulting R258L, located substrate recognition site 3 ERG11, was identified. finding suggests association newly phenotype gattii. Further investigations needed determine exact role R258L plays decreased as well participation additional drugs. IMPORTANCE The species human pathogens drug or other management challenges exist. Here, we report differential among species, some displaying resistant phenotypes. Azoles most commonly used drugs infections. Our findings underscore necessity antifungal setting order assist patient beneficial outcomes. an change sequence protein might be these Identifying understanding affect affinity will eventually aid design new overcome global growing concern resistance.

Language: Английский

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Genotypic diversity and antifungal susceptibility of Cryptococcus neoformans species complex from China, including the diploid VNIII isolates from HIV-infected patients in Chongqing region

Medical Mycology, Journal Year: 2023, Volume and Issue: 61(12)

Published: Nov. 15, 2023

Although previous studies on the genotypic diversity and antifungal susceptibility of Cryptococcus neoformans species complex (CNSC) isolates from China revealed ST5 genotype being dominant, information about CNSC Chinese HIV-infected patients is limited. In this study, 171 in Chongqing region Southwest were genotyped using International Society for Human Animal Mycology-multilocus sequence typing consensus scheme, their drug susceptibilities determined following CLSI M27-A3 guidelines. Among isolates, six types (STs) identified, including dominant newly reported ST15, four diploid VNIII (ST632/ST636). Moreover, a total 1019 with STs HIV-status collected analyzed Mainland present study. A minimum spanning analysis grouped these into three main subgroups, which dominated by clonal (CC5), followed ST31 (CC31) ST93 (CC93). The trend resistance or decreasing clinical to azole agents within increasing, especially fluconazole.In paper, novel ST15 (ST632/ST636) found China, evidence fluconazole. we clustered so far major subgroups.

Language: Английский

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