Biology subjects

Dufresne, P.

Publications and source records attributed to Dufresne, P..

3 recordsLinked to original sources

bioRxiv2025

Antifungal susceptibility profile of clinically relevant species of the genus Sporothrix: establishment of Epidemiological Cutoff Values (ECVs) according to CLSI broth microdilution methodology

Sporotrichosis is a globally distributed subcutaneous mycosis caused mainly by Sporothrix brasiliensis, S. schenckii, and S. globosa. Cat-transmitted sporotrichosis, primarily caused by S. brasiliensis in South America and to a lesser extent by S. schenckii in Southeast Asia, is emerging as a significant public health concern, due its outbreak potential. Itraconazole is the first-choice drug for treatment of human and cats, but reduced susceptibility has been reported based on previously proposed epidemiological cut-off values (ECVs). To support resistance surveillance, we aimed to establish CLSI-endorsed ECVs for these clinically relevant Sporothrix species. A total of 3,588 minimum inhibitory concentration (MIC) values for seven antifungal agents (amphotericin B, itraconazole, posaconazole, voriconazole, isavuconazole, olorofim, and terbinafine) were obtained from 19 international laboratories. Four of seven antifungals met the CLSI M57 guidelines criteria to determine the ECV. Established ECVs for amphotericin B were found to be high with 8 {micro}g/mL for S. brasiliensis and S. globosa, and 4 {micro}g/mL for S. schenckii. Itraconazole ECVs were 4 {micro}g/mL for S. brasiliensis and S. schenckii. Posaconazole ECVs were 4 {micro}g/mL for all three species (tentative for S. globosa), while the terbinafine ECV for S. brasiliensis was 0.12 {micro}g/mL. Olorofim demonstrated good in vitro activity, particularly against S. brasiliensis. Overall, this study establishes validated ECVs for key antifungals against Sporothrix species and identifies a low prevalence of non-wild type (NWT) isolates, supporting ongoing antifungal resistance monitoring.

microbiology↗

bioRxiv2024

FungAMR: A comprehensive portrait of antimicrobial resistance mutations in fungi

Antimicrobial resistance (AMR) is a global threat. To optimize the use of our antifungal arsenal, we need rapid detection and monitoring tools that rely on high-quality AMR mutation data. Here, we performed a thorough manual curation of published AMR mutations in fungal pathogens to produce the FungAMR reference dataset. A total of 501 papers were curated, leading to 35,792 mutation entries all classified with the degree of evidence that supports their role in resistance. FungAMR covers 95 species, 246 genes and 208 drugs. We combined variant effect predictors with FungAMR resistance mutations and showed that these tools could be used to help predict the potential impact of mutations on AMR. Additionally, a comparative analysis among species revealed a high level of convergence in the molecular basis of resistance, highlighting some potentially universal resistance mutations. The analysis also showed that a significant number of resistance mutations lead to cross-resistance within antifungals of a class, as well as between classes for certain mutated genes. The acquisition of fungal resistance in the clinic and the field is an urging concern. Finally, we provide a computational tool, ChroQueTas, that leverages FungAMR to screen fungal genomes for AMR mutations. These resources are anticipated to have great utility for researchers in the fight against antifungal resistance.

microbiology↗

bioRxiv2018

Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus.

Dynamic trafficking of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs) to synapses is critical for activity-dependent synaptic plasticity underlying learning and memory, however the identity of key molecular effectors remains elusive. Here, we demonstrate that membrane depolarization and N-methyl-D-aspartate receptor (NMDAR) activation triggers secretion of the chemotropic guidance cue netrin-1 from dendrites. Using selective genetic deletion, we show that netrin-1 expression by excitatory neurons is required for NMDAR-dependent long-term potentiation (LTP) in the adult hippocampus. Further, we demonstrate that application of exogenous netrin-1 is sufficient to trigger the potentiation of excitatory glutamatergic transmission at hippocampal Schaffer collateral synapses via Ca2+-dependent recruitment of GluA1-containing AMPARs, promoting the maturation of immature or nascent synapses. These findings identify a central role for activity-dependent release of netrin-1 as a critical effector of synaptic plasticity in the adult hippocampus.

neuroscience↗