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Almeida-Paes, R.

Publications and source records attributed to Almeida-Paes, R..

2 recordsLinked to original sources

Telomeric assemblies of Paracoccidioides genomes

Paracoccidioides is a genus of dimorphic fungal pathogens endemic to Latin America. We generated long-read de novo assemblies for 11 isolates representing four species of the brasiliensis complex (P. brasiliensis, P. americana, P. restrepiensis, P. venezuelensis) and P. lutzii. These include the first complete telomere-to-telomere assemblies for P. brasiliensis (Pb18) and P. americana (Pb03), each with five chromosomes. Comparative analyses revealed chromosomal fusion and fission events distinguishing P. brasiliensis and P. americana, and a 90 kb tandem duplication in P. americana containing siderophore biosynthesis genes (sid1, sid3, sid4), a cluster of putative virulence factors. Mitochondrial genomes showed conserved gene order but a phylogenetic topology inconsistent with the nuclear tree, suggesting mitochondrial introgression between P. lutzii and P. venezuelensis. RNA transposable elements were enriched near telomeres, correlated with genome size, and most abundant in P. lutzii. These assemblies provide key resources for understanding genome evolution and introgression in Paracoccidioides. SIGNIFICANCESpecies of Paracoccidioides cause paracoccidioidomycosis, a systemic mycosis that remains a major public health problem in Latin America. Despite their clinical importance, genome evolution across the genus is poorly understood owing to the lack of complete reference assemblies. Here, we present the first telomere-to-telomere reference genomes for P. brasiliensis and P. americana, enabling a comprehensive comparison of chromosomal structure across the genus. Our analyses reveal that the nuclear genome is highly dynamic and shaped by large-scale rearrangements and structural variants, including the duplication of a siderophore biosynthesis-related gene cluster linked to virulence. In contrast, the mitochondrial genome is structurally conserved but shows introgression between species, revealing hidden evolutionary exchange. Together, these genomic resources redefine our understanding of Paracoccidioides evolution and provide a foundation for advances in molecular diagnostics, epidemiological surveillance, and studies of fungal pathogenicity.

microbiology↗

A screening of the MMV Pathogen Box(R) reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis

Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds with in vitro antifungal activity in the Pathogen Box(R) compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1M was performed with a Fonsecaea pedrosoi clinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii, Phialophora verrucosa, Exophiala jeanselmei, Exophiala dermatitidis, Fonsecaea monophora, Fonsecaea nubica, and Rhinocladiella similis) at concentrations ranging from 0.039 to 10 M. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of the F. pedrosoi growth: difenoconazole, bitertanol, iodoquinol, azoxytrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25 - 2.5M) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10M). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against the C. carrionii isolate. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.

microbiology↗