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

Abstract

Streptococcus equi subsp. zooepidemicus is an important pathogen in horses that causes severe diseases such as pneumonia and abortion. Furthermore, it is a zoonotic agent, and contact with horses is a known risk factor. In this study, we investigated the working hypothesis that the zoonotic potential varies among S. equi subsp. zooepidemicus 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 S. equi subsp. zooepidemicus strains that the M-like protein SzM is crucial for the binding of fibrinogen to the bacterial surface and for survival in equine and human blood. S. equi subsp. zooepidemicus isolates of equine and human origins were compared with regard to SzM sequences and binding of equine and human fibrinogens. The N-terminal 216 amino acids 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 S. equi subsp. zooepidemicus isolates but much less so in equine S. equi subsp. zooepidemicus 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 S. equi subsp. zooepidemicus isolates.

Genetic characterization of Streptococcus equi subspecies zooepidemicus associated with high swine mortality in the United States

“…Putative virulence genes were retrieved from genome sequences according to previous publications (Alber et al., 2005; Bergmann et al., 2019; Kittang et al., 2017; Ma et al., 2019; Rash et al., 2014). The prediction of genomic island (GI) was based on IslandPath‐DIMOB, SIGI‐HMM, IslandPick and Islander using IslandViewer 4 (Bertelli et al., 2017).…”

“…The presence of 15 putative virulence genes, which have been previously reported in S. zooepidemicus (Alber et al, 2005;Bergmann et al, 2019;Kittang et al, 2017;Ma et al, 2019;Rash et al, 2014), was examined in all 48 isolates included in this study ( Figure 5, Table S7). (Alber et al, 2005;Paillot, Darby, et al, 2010;Xu et al, 2019).…”

Genetic characterization ofStreptococcus equisubspecieszooepidemicusassociated with high swine mortality in United States

“…Putative virulence genes were retrieved from genome sequences according to previous publications ( 13, 24–27 ). The prediction of genomic island (GI) was based on IslandPath-DIMOB, SIGI-HMM, IslandPick and Islander using IslandViewer 4 ( 28 ).…”

Pathogenicity and drug resistance of animal streptococci responsible for human infections

“…SEZ causes infections of the nasopharynx, lungs, lymph nodes and MALDI-TOF MS [191] the urinary tract in animals [82,86,87]. This microorganism caused an epidemic of respiratory diseases among several thousand Icelandic horses in 2010 [68,83,88]. Skive et al [89] demonstrated the viability of SEZ in the endometrium, suggesting its intracellular viability.…”

“…SEZ causes infections of the nasopharynx, lungs, lymph nodes and the urinary tract in animals [82, 86, 87]. This microorganism caused an epidemic of respiratory diseases among several thousand Icelandic horses in 2010 [68, 83, 88]. Skive et al .…”