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Evolution of virulence-related phenotypes of Sporothrix brasiliensis isolates from patients with chronic sporotrichosis and acquired immunodeficiency syndrome.

ABSTRACT: Sporotrichosis in immunocompromised patients has a high morbidity and may cause deaths. Particularly, patients with acquired immunodeficiency syndrome (AIDS) with low T CD4 counts develop a chronic disease, with severe and widespread forms. Recently, the ability of Sporothrix brasiliensis, the main agent of zoonotic sporotrichosis, to increase its virulence in a diabetic patient without HIV infection was described. Since it was a unique finding, it is not known how often this occurs in patients with chronic and refractory sporotrichosis. The aim of this study is to compare sequential Sporothrix isolates obtained from patients with sporotrichosis and AIDS in order to detect changes in virulence-related phenotypes and acquisition of antifungal resistance during the evolution of the disease. Fungal growth in different substrates, antifungal susceptibility, thermotolerance, resistance to oxidative stress, and production of hydrolytic enzymes were evaluated. Correlations were assessed between clinical and phenotypic variables. Sixteen isolates, all identified as S. brasiliensis, obtained from five patients were studied. They grew well on glucose and N-acetyl-D-glucosamine, but poorly on lactate. Except from isolates collected from two patients, which were non-wild type for terbinafine, they were considered wild type for the antifungal drugs tested. Thermotolerance of the isolates was moderate to high. Except for phytase and phospholipase, isolates were able to produce virulence-related enzymes on different levels. Changes in all studied phenotypes were observed during the course of the disease in some patients. The results show that the HIV-driven immunosuppression is more relevant than fungal phenotypes on the unfavorable outcomes of disseminated sporotrichosis.

SUBMITTER: Cruz ILR

PROVIDER: S-EPMC7966698 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: The fungal genus Sporothrix includes at least four human pathogenic species. One of these species, S. brasiliensis, is the causal agent of a major ongoing zoonotic outbreak of sporotrichosis in Brazil. Elsewhere, sapronoses are caused by S. schenckii and S. globosa. The major aims on this comparative genomic study are: 1) to explore the presence of virulence factors in S. schenckii and S. brasiliensis; 2) to compare S. brasiliensis, which is cat-transmitted and infects both humans and cats with S. schenckii, mainly a human pathogen; 3) to compare these two species to other human pathogens (Onygenales) with similar thermo-dimorphic behavior and to other plant-associated Sordariomycetes. RESULTS: The genomes of S. schenckii and S. brasiliensis were pyrosequenced to 17x and 20x coverage comprising a total of 32.3 Mb and 33.2 Mb, respectively. Pair-wise genome alignments revealed that the two species are highly syntenic showing 97.5% average sequence identity. Phylogenomic analysis reveals that both species diverged about 3.8-4.9 MYA suggesting a recent event of speciation. Transposable elements comprise respectively 0.34% and 0.62% of the S. schenckii and S. brasiliensis genomes and expansions of Gypsy-like elements was observed reflecting the accumulation of repetitive elements in the S. brasiliensis genome. Mitochondrial genomic comparisons showed the presence of group-I intron encoding homing endonucleases (HE's) exclusively in S. brasiliensis. Analysis of protein family expansions and contractions in the Sporothrix lineage revealed expansion of LysM domain-containing proteins, small GTPases, PKS type1 and leucin-rich proteins. In contrast, a lack of polysaccharide lyase genes that are associated with decay of plants was observed when compared to other Sordariomycetes and dimorphic fungal pathogens, suggesting evolutionary adaptations from a plant pathogenic or saprobic to an animal pathogenic life style. CONCLUSIONS: Comparative genomic data suggest a unique ecological shift in the Sporothrix lineage from plant-association to mammalian parasitism, which contributes to the understanding of how environmental interactions may shape fungal virulence. . Moreover, the striking differences found in comparison with other dimorphic fungi revealed that dimorphism in these close relatives of plant-associated Sordariomycetes is a case of convergent evolution, stressing the importance of this morphogenetic change in fungal pathogenesis.

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Evolution of virulence-related phenotypes of Sporothrix brasiliensis isolates from patients with chronic sporotrichosis and acquired immunodeficiency syndrome.

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