Antimicrobial resistance patterns in Streptococcus dysgalactiae in a One Health perspective.

Background: Streptococcus dysgalactiae (SD) is an important pathogen in humans as well as in a broad range of animal species. Escalating rates of antibiotic resistance in SD has been reported in both human and veterinary clinical practice, but the dissemination of resistance determinants has so far never been examined in a One Health Perspective. We wanted to explore the occurrence of zoonotic transmission of SD and the potential for exchange of resistance traits between SD from different host populations. Methods: We compared whole genome sequences and phenotypical antimicrobial susceptibility of 407 SD isolates, comprising all isolates obtained from human bloodstream infections in 2018 (n = 274) and available isolates associated with animal infections from the years 2018 and 2019 (n = 133) in Norway. Results: Antimicrobial resistance genes were detected in 70 (26%), 9 (25%) and 2 (2%) of the isolates derived from humans, companion animals and livestock, respectively. Notably, distinct host associated genotypic resistomes were observed. The erm(A) gene was the dominant cause of erythromycin resistance in human associated isolates, whereas only erm(B) and lsa(C) were identified in SD isolates from animals. Moreover, the tetracycline resistance gene tet(O) was located on different mobile genetic elements in SD from humans and animals. Evidence of niche specialization was also evident in the phylogenetic analysis, as the isolates could be almost perfectly delineated in accordance with host species. Nevertheless, near identical mobile genetic elements were observed in four isolates from different host species including one human, implying potential transmission of antibiotic resistance between different environments. Conclusion: We found a phylogenetic delineation of SD strains in line with host adapted populations and niche specialization. Direct transmission of strains or genetic elements carrying resistance genes between SD from different ecological niches appears to be rare in our geographical region.

Streptococcus dysgalactiae Bloodstream Infections, Norway, 1999-2021.

Streptococcus dysgalactiae increasingly is recognized as a pathogen of concern for human health. However, longitudinal surveillance data describing temporal trends of S. dysgalactiae are scarce. We retrospectively identified all ß-hemolytic streptococcal bloodstream infections reported in Bergen, in western Norway, during 1999-2021. To explore S. dysgalactiae disease burden in a broader context, we mapped the incidence of all microbial species causing bloodstream infections during 2012-2021. We found S. dysgalactiae incidence rates substantially increased during the study period; by 2021, S. dysgalactiae was the fifth most common pathogen causing bloodstream infections in our region. We noted genotypic shifts and found that the rising trend was related in part to the introduction and expansion of the stG62647 emm-type. S. dysgalactiae is among the most common causes of bloodstream infections in western Norway, and increased surveillance and unambiguous species identification are needed to monitor the disease burden attributable to this pathogen.

Clinical and molecular characteristics of infective ß-hemolytic streptococcal endocarditis.

Streptococcus pyogenes (S. pyogenes) and Streptococcus dysgalactiae subspecies equisimilis (SDSE) cause considerable morbidity and mortality, and show similarities in disease manifestations and pathogenic mechanisms. Their involvement in infective endocarditis, however, has not been well described. Invasive S. pyogenes and SDSE infections in Health Region Bergen, Norway, in the period 1999-2013 were reviewed, and sixteen cases of endocarditis were identified. The median duration of symptoms was 2.5days, the frequency of embolic events 50%, 38% received valve replacement and the 30-day mortality was 25%. In S. pyogenes, a significant correlation was observed between the repertoire of fibronectin-binding genes, phenotypic binding ability to fibronectin and disease manifestations. Conversely, no associations between phenotypic and genotypic characteristics were detected in SDSE. S. pyogenes and SDSE endocarditis is characterized by rapid and severe clinical manifestations. The pathogenesis is multifactorial, but our results infer a potential role of fibronectin binding in the development of S. pyogenes endocarditis.

New tricks from an old cow: infective endocarditis caused by Streptococcus dysgalactiae subsp. dysgalactiae.

We present a case of infective endocarditis caused by Streptococcus dysgalactiae subsp. dysgalactiae, a major cause of bovine mastitis and previously thought to be an animal-restricted pathogen. The patient reported no direct contact with animals, and the clinical course was severe and complicated.

Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells.

Dysfunction of glial lipid metabolism and abnormal myelination has recently been reported in both schizophrenia and bipolar disorder. Cholesterol is a major component of myelin, and glia-produced cholesterol serves as a glial growth factor in synaptogenesis. We have recently demonstrated that antipsychotic drugs activate the sterol regulatory element-binding protein (SREBP) transcription factors in human and rat glial cells, with subsequent up-regulation of numerous downstream genes involved in cholesterol and fatty acid biosynthesis. Since this stimulation of cellular lipogenesis could represent a new mechanism of action of psychotropic drugs, we investigated whether antidepressants and mood-stabilizers were able to induce a similar activation of SREBP-controlled lipid biosynthesis. Cultured human glioma cells (GaMg) were exposed to the antidepressant drugs imipramine, amitriptyline, clomipramine, citalopram, fluoxetine, mirtazapine and bupropion and the mood-stabilizers/antiepileptics lithium, valproate and carbamazepine. All antidepressant drugs activated the SREBP system with subsequent up-regulation of the downstream lipogenesis-related genes, although to a markedly different extent. The mood-stabilizers did not affect the SREBPs or the downstream genes. These results link antidepressant drugs, but not mood-stabilizers, to SREBP-mediated activation of cellular lipogenesis, and demonstrate a functional similarity between antipsychotic and antidepressant molecular drug action.