Prominent binding of human and equine fibrinogen to Streptococcus equi subsp. zooepidemicus is mediated by specific SzM-types and is a distinct phenotype of zoonotic isolates

Streptococcus equi subsp. zooepidemicus (SEZ) is an important pathogen in horses causing severe diseases such as pneumonia and abortion. Furthermore, it is a zoonotic agent and contact to horses is a known risk factor. In this study, we investigated the working hypothesis that the zoonotic potential varies among SEZ strains in association with differences in M-like protein-mediated binding of host plasma proteins. We demonstrate via in-frame deletion mutagenesis of two different SEZ strains that the M-like protein SzM is crucial for binding of fibrinogen to the bacterial surface and for survival in equine and human blood. SEZ isolates of equine and human origin were compared with regard to SzM sequences and binding of equine and human fibrinogen. The N-terminal 216 amino acids (aa) of the mature SzM were found to exhibit a high degree of diversity, but the majority of human isolates grouped in three distinct SzM clusters. Plasma protein absorption assays and flow cytometry analysis revealed that pronounced binding of human fibrinogen is a common phenotype of human SEZ isolates but much less so in equine SEZ isolates. Furthermore, binding of human fibrinogen is associated with specific SzM types. These results suggest that SzM-mediated binding of human fibrinogen is an important virulence mechanism of zoonotic SEZ isolates.