Differences in Cell Morphometry, Cell Wall Topography and Gp70 Expression Correlate with the Virulence of Sporothrix brasiliensis Clinical Isolates

Abstract

Sporotrichosis is a chronic infectious disease affecting both humans and animals. For many years, this subcutaneous mycosis had been attributed to a single etiological agent; however, it is now known that this taxon consists of a complex of at least four pathogenic species, including Sporothrix schenckii and Sporothrix brasiliensis. Gp70 was previously shown to be an important antigen and adhesin expressed on the fungal cell surface and may have a key role in immunomodulation and host response. The aim of this work was to study the virulence, morphometry, cell surface topology and gp70 expression of clinical isolates of S. brasiliensis compared with two reference strains of S. schenckii. Several clinical isolates related to severe human cases or associated with the Brazilian zoonotic outbreak of sporotrichosis were genotyped and clustered as S. brasiliensis. Interestingly, in a murine subcutaneous model of sporotrichosis, these isolates showed a higher virulence profile compared with S. schenckii. A single S. brasiliensis isolate from an HIV-positive patient not only showed lower virulence but also presented differences in cell morphometry, cell wall topography and abundant gp70 expression compared with the virulent isolates. In contrast, the highly virulent S. brasiliensis isolates showed reduced levels of cell wall gp70. These observations were confirmed by the topographical location of the gp70 antigen using immunoelectromicroscopy in both species. In addition, the gp70 molecule was sequenced and identified using mass spectrometry, and the sequenced peptides were aligned into predicted proteins using Blastp with the S. schenckii and S. brasiliensis genomes.

Asexual Propagation of a Virulent Clone Complex in a Human and Feline Outbreak of Sporotrichosis

“…Infection assays using mouse models revealed a higher virulence of S. brasiliensis than of S. schenckii, supporting the spread of virulent clone complexes in sporotrichosis epidemics (17,64). According to the phylogenetic trees (see Fig.…”

<i>Sporothrix brasiliensis</i>: aspectos imunol&oacute;gicos e virul&ecirc;ncia

“…Th1 e Th17 são elementos fundamentais na resposta imune frente a S. schenckii (FRANCO et al, 2012;ALMEIDA et al, 2015;FERREIRA et al, 2015;VERDAN et al, 2012;LIU et al, 2016). Estudos mostram que não só o IFN-γ é secretado durante a imunização passiva, mas que IL-10 e IL-4 também aumentaram durante o período de infecção, sugerindo um padrão misto de resposta Th1 / Th2 (ALMEIDA et al, 2015).…”

“…Estudos mostram que não só o IFN-γ é secretado durante a imunização passiva, mas que IL-10 e IL-4 também aumentaram durante o período de infecção, sugerindo um padrão misto de resposta Th1 / Th2 (ALMEIDA et al, 2015).…”

“…Sabe-se que anticorpos protetores e as células CD4+ Th1 e Th17 são elementos fundamentais na resposta imune frente a S. schenckii (FRANCO et al, 2012;ALMEIDA et al, 2015;FERREIRA et al, 2015;VERDAN et al, 2012;LIU et al, 2016). As citocinas padrão Th17 estão sabidamente envolvidas no controle de infecções causadas pelos fungos Candida e Aspergillus, particularmente em condições de deficiência de resposta Th1 (ROMANI, 2011).…”

“…é a glicoproteína de 70kDa (gp70) (NASCIMENTO et al, 2008). Esta glicoproteína está localizada na superfície de isolados de S. schenckii e S. brasiliensis, sendo capaz de mediar a interação do fungo à fibronectina (CASTRO et al, 2013). Contudo, análises da expressão de gp70 mostraram q ue ela é pouco expressa na superfície das leveduras da cepa S. brasiliensis ATCC MyA-4823.…”