Abstract
Sporotrichosis is a polymorphic chronic infection of humans and animals classically acquired after traumatic inoculation with soil and plant material contaminated with Sporothrix spp. propagules. An alternative and successful route of transmission is bites and scratches from diseased cats, through which Sporothrix yeasts are inoculated into mammalian tissue. The development of a murine model of subcutaneous sporotrichosis mimicking the alternative route of transmission is essential to understanding disease pathogenesis and the development of novel therapeutic strategies. To explore the impact of horizontal transmission in animals (e.g., cat-cat) and zoonotic transmission on Sporothrix fitness, the left hind footpads of BALB/c mice were inoculated with 5×106 yeasts (n = 11 S. brasiliensis, n = 2 S. schenckii, or n = 1 S. globosa). Twenty days post-infection, our model reproduced both the pathophysiology and symptomology of sporotrichosis with suppurating subcutaneous nodules that progressed proximally along lymphatic channels. Across the main pathogenic members of the S. schenckii clade, S. brasiliensis was usually more virulent than S. schenckii and S. globosa. However, the virulence in S. brasiliensis was strain-dependent, and we demonstrated that highly virulent isolates disseminate from the left hind footpad to the liver, spleen, kidneys, lungs, heart, and brain of infected animals, inducing significant and chronic weight loss (losing up to 15% of their body weight). The weight loss correlated with host death between 2 and 16 weeks post-infection. Histopathological features included necrosis, suppurative inflammation, and polymorphonuclear and mononuclear inflammatory infiltrates. Immunoblot using specific antisera and homologous exoantigen investigated the humoral response. Antigenic profiles were isolate-specific, supporting the hypothesis that different Sporothrix species can elicit a heterogeneous humoral response over time, but cross reaction was observed between S. brasiliensis and S. schenckii proteomes. Despite great diversity in the immunoblot profiles, antibodies were mainly derived against 3-carboxymuconate cyclase, a glycoprotein oscillating between 60 and 70 kDa (gp60-gp70) and a 100-kDa molecule in nearly 100% of the assays. Thus, our data broaden the current view of virulence and immunogenicity in the Sporothrix-sporotrichosis system, substantially expanding the possibilities for comparative genomic with isolates bearing divergent virulence traits and helping uncover the molecular mechanisms and evolutionary pressures underpinning the emergence of Sporothrix virulence.
Highlights
Recent years have seen a global burden of fungal infections in warm-blooded hosts, many of which have the potential to trigger epidemics or cause endemic diseases [1]
Sporotrichosis is polymorphic infection that is acquired after traumatic implantation of Sporothrix propagules into host tissues
We explored a subcutaneous murine model of sporotrichosis mimicking the alternative route of transmission considering animal horizontal transmission and zoonotic transmission in which S. brasiliensis yeasts are inoculated
Summary
Recent years have seen a global burden of fungal infections in warm-blooded hosts, many of which have the potential to trigger epidemics or cause endemic diseases [1]. Sporotrichosis is a chronic infection of humans and animals caused by Sporothrix species in the order Ophiostomatales, which is mainly composed of saprophytic fungi. A pathogenic group consisting of four species (Sporothrix brasiliensis, Sporothrix schenckii, Sporothrix globosa, and Sporothrix luriei) has emerged as an important threat to the health of several warm-blooded hosts around the globe [2]. S. brasiliensis is by far the most virulent, followed by S. schenckii and S. globosa [8, 9], but all of them are capable of disease in mostly healthy patients [10]. Fernandes et al [8] confirmed differential virulence in the S. schenckii clade (pathogenic clade) and proposed a correlation among protein secretion, immunogenicity, genetic diversity, and virulence
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