Pathogenicity Induced by Invasive Infection of Streptococcus dysgalactiae subsp. equisimilis in a Mouse Model of Diabetes

Abstract

Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes severe invasive diseases such as streptococcal toxic shock syndrome, similar to that caused by S. pyogenes (GAS). Invasive SDSE infections are increasing, particularly among patients with diabetes mellitus. Here we investigate the association between the pathogenicity of SDSE and diabetes mellitus in a mouse model, using GAS infection for comparison. Intraperitoneal injection of highly hemolytic SDSE-167 into C57BL6/J mice induced a rapid rise in blood glucose concentrations within 4 h, which was otherwise seen only in mice injected with high doses of hypervirulent GAS mutants. The survival rates of mice injected with SDSE-167 were significantly lower in mice (db/db) with type 2 diabetes than in nondiabetic mice. Injection of db/db mice with SDSE-167 increased the concentrations of cytokines and chemokines, particularly those of interleukin 6 and monocyte chemotactic protein-1. Microarray data indicate that multiple pathways are involved in the pathogenicity of SDSE-167 in db/db mice. These data reveal that the mechanisms underlying streptococcal infection differ between SDSE and GAS.

Group A, B, C, and G Streptococcus Lancefield antigen biosynthesis is initiated by a conserved α-d-GlcNAc-β-1,4-l-rhamnosyltransferase

“…Many species within the Lactobacillales order present a surface RhaPS intertwined with additional components of the thick cell wall that is typical of Gram-positive bacteria. These surface glycans, as with other critical peptidoglycan-anchored structures, are essential for cell viability and play an essential role in pathogenesis (7, 9, 15, 24, 36, 40–42). In the Streptococcus genus, in particular in S. pyogenes , S. agalactiae , and S. mutans , genetic studies conducted on S. pyogenes strains showed that the absence of rhamnose glycopolymers results in severe growth defects associated with an altered cell wall and an increased susceptibility to muralytic enzymes (7, 25, 43, 43–45).…”

Pathogenicity Characterization of Prevalent-Type Streptococcus dysgalactiae subsp. equisimilis Strains

“…In the present study, we did not utilize any disease model of mice. We previously reported that intraperitoneal injection of SDSE to diabetic mice resulted in the abundant release of inflammatory cytokines, chemokines, and damages associated with molecular patterns, whereas injection into wild-type mice did not (Ogura et al, 2018); this suggested that pathogenicity of SDSE varies depending on the underlying diseases of the host. To elucidate SDSE pathogenicity, further analysis using disease model mice is required.…”

“…The mean age of adult patients with invasive SDSE infection was older than those infected with GAS (Cohen-Poradosu et al, 2004;Wajima et al, 2016). Our group reported that an SDSE strain causes severe pathogenicity to diabetic mice compared with GAS strains (Ogura et al, 2018). Genteluci et al (2015) reported that 59.3% of the 118 SDSE clinical isolates were able to form biofilm in vitro, and all of the strains formed biofilm in mice.…”

“…The hemolytic activity of SDSE strains was measured as described previously (Ogura et al, 2018). SDSE strains were cultured overnight in THY medium supplemented with 1% Tween 80 (Sigma Aldrich, St. Louis, MO, United States), centrifuged at 1500 × g, and resuspended in fresh THY medium at OD 600 = 1.0.…”

Novel Hyaluronate Lyase Involved in Pathogenicity of Streptococcus dysgalactiae subsp. equisimilis

“…Most patients who present with SDSE bacteremia have other co-morbidities such as malignant tumors and diabetes mellitus (Broyles et al, 2009;Rantala, 2014). We previously explored physiologic responses to these bacteria and found that SDSE is particularly lethal in diabetic mice (Ogura et al, 2018). In this study, we focused on the relationship between HA degradation and pathogenic disease associated with SDSE.…”