Streptococcus suis, both a common colonizer of the porcine upper respiratory tract and an invasive pig pathogen, successfully adapts to different host environments encountered during infection. Whereas the initial infection mainly occurs via the respiratory tract, in a second step, the pathogen can breach the epithelial barrier and disseminate within the whole body. Thereby, the pathogen reaches other organs such as the heart, the joints, or the brain. In this review, we focus on the role of S. suis metabolism for adaptation to these different in vivo host niches to encounter changes in nutrient availability, host defense mechanisms and competing microbiota. Furthermore, we highlight the close link between S. suis metabolism and virulence. Mutants deficient in metabolic regulators often show an attenuation in infection experiments possibly due to downregulation of virulence factors, reduced resistance to nutritive or oxidative stress and to phagocytic activity. Finally, metabolic pathways as potential targets for new therapeutic strategies are discussed. As antimicrobial resistance in S. suis isolates has increased over the last years, the development of new antibiotics is of utmost importance to successfully fight infections in the future.

Streptococcus suis is a common pathogen colonising the respiratory tract of pigs. It can cause meningitis, sepsis and pneumonia leading to economic losses in the pig industry worldwide. Cyclooxygenase-2 (COX-2) and its metabolites play an important regulatory role in different biological processes like inflammation modulation and immune activation. In this report we analysed the induction of COX-2 and the production of its metabolite prostaglandin E₂ (PGE₂) in a porcine precision-cut lung slice (PCLS) model. Using Western blot analysis, we found a time-dependent induction of COX-2 in the infected tissue resulting in increased PGE₂ levels. Immunohistological analysis revealed a strong COX-2 expression in the proximity of the bronchioles between the ciliated epithelial cells and the adjacent alveolar tissue. The morphology, location and vimentin staining suggested that these cells are subepithelial bronchial fibroblasts. Furthermore, we showed that COX-2 expression as well as PGE₂ production was detected following infection with two prevalent S. suis serotypes and that the pore-forming toxin suilysin played an important role in this process. Therefore, this study provides new insights in the response of porcine lung cells to S. suis infections and serves as a basis for further studies to define the role of COX-2 and its metabolites in the inflammatory response in porcine lung tissue during infections with S. suis.

Streptococcus suis, a common member of the porcine respiratory microbiota, can cause life-threatening diseases in pigs as well as humans. A previous study identified the gene trpX as conditionally essential for in vivo survival by intrathecal infection of pigs with a transposon library of S. suis strain 10. Here, we characterized trpX, encoding a putative tryptophan/tyrosine transport system substrate-binding protein, in more detail. We compared growth capacities of the isogenic trpX-deficient mutant derivative strain 10∆trpX with its parent. Growth experiments in chemically defined media (CDM) revealed that growth of 10∆trpX depended on tryptophan concentration, suggesting TrpX involvement in tryptophan uptake. We demonstrated that trpX is part of an operon structure and co-transcribed with two additional genes encoding a putative permease and ATPase, respectively. Bioinformatics analysis identified a putative tryptophan T-box riboswitch in the 5′ untranslated region of this operon. Finally, qRT-PCR and a reporter activation assay revealed trpX mRNA induction under tryptophan-limited conditions. In conclusion, our study showed that TrpX is part of a putative tryptophan ABC transporter system regulated by a T-box riboswitch probably functioning as a substrate-binding protein. Due to the tryptophan auxotrophy of S. suis, TrpX plays a crucial role for metabolic adaptation and growth during infection.

Bordetella bronchiseptica is a gram-negative bacterium contributing to respiratory diseases in many different animal species. In the swine population, it occurs frequently and plays a role in the Porcine Respiratory Disease Complex as well as in the pathogenesis of atrophic rhinitis. The dermonecrotic toxin (DNT) is involved in the destruction of the nasal conchae, a hallmark of atrophic rhinitis, and several studies have shown the effects of DNT on osteoblastic cells. Surprisingly, only little is known about the interactions of DNT and respiratory epithelial cells. Thus, we investigated the influence of DNT on porcine respiratory epithelial cells during mono- and co-infections in vitro . For this, we infected porcine precision-cut lung slices and air-liquid interface cultures with a DNT-positive B. bronchiseptica wild-type strain and its isogenic DNT-deficient mutant strain. For co-infection experiments, a Streptococcus suis serotype 2 wild-type strain was used. We evaluated cytotoxic effects and colonization of both pathogens, as well as the pro-inflammatory cytokine response of the host cells. Remarkably, DNT neither contributed to the cytotoxic effects of B. bronchiseptica nor did it affect bacterial colonization. Regarding the cytokine response, pro-inflammatory cytokines were expressed mainly upon infection with B. bronchiseptica but hardly after infection with S. suis , whereas co-infection with both pathogens had an amplifying effect on cytokine expression after prolonged infection, independently of DNT. Concluding, we found no evidence that DNT contributes to the early stages of infection with B. bronchiseptica and S. suis in in vitro models of the porcine respiratory tract.

Streptococcus suis is a Gram-positive bacterium with a dual role as a commensal member of the porcine nasal microbiota and a pathogen causing systemic disease in pigs and humans. Mounting evidence suggests that metabolism is a key driver of S. suis pathogenicity. Given the species' high genetic variability, we hypothesize that differences in metabolic networks could explain the diverse pathogenic phenotypes observed across different strains. To test this, we generated an atlas of over 3000 strain-specific and automatically curated genome-scale metabolic models that cover the breadth of pathogenic and commensal S. suis lineages. Using this model atlas, we performed the first species-level examination of metabolic traits in S. suis. Our simulations, supported by experimental validation, revealed three key insights. First, while metabolic traits are broadly conserved in S. suis, there are nevertheless lineage-dependent differences in amino acid auxotrophies and carbon utilization patterns that point towards distinct in vivo niches. Second, most strains are predicted to grow in different plausible in vivo environments regardless of their virulence phenotype, suggesting that metabolism is a weak barrier to systemic infection. Third, by systematically predicting reaction essentiality in more than 15 million reaction-strain-condition combinations, we identify a subset of 17 reactions, largely in nucleotide metabolism, that are conditionally essential in vivo and may serve as new targets for the development of new antimicrobials or vaccines. Overall, this study provides a valuable new resource for broadly examining S. suis metabolism and its role in pathogenicity.

Antimicrobial resistance (AMR) is a complex and rapidly evolving global health challenge that requires well-trained professionals within a One Health framework. However, AMR education remains fragmented, with limited interdisciplinary integration and inconsistencies across disciplines. Although AMR is included in undergraduate and postgraduate curricula in human medicine, veterinary medicine, biological sciences, and pharmacology, the educational focus differs substantially between fields. Moreover, teaching focuses on biomedical and pharmacological aspects, while social, behavioural, and policy dimensions are often underrepresented, limiting the ability to address AMR as a multifaceted societal challenge. To identify gaps in AMR teaching, associated challenges and unmet educational resource needs, we conducted a three-month international survey among professionals from diverse scientific fields involved in AMR teaching. A total of 85 professionals participated in the survey, of whom 94% were actively involved in AMR teaching. AMR was most often taught within microbiology (35%) or health-related (33%) courses and was typically presented as few lectures within a module (33%). Although the general perception was that engaging teaching approaches, such as case-based learning, better support effective learning, many participants (31%) reported relying primarily on traditional lecture-based materials. Furthermore, the survey identified limited curriculum time, behavioural barriers, and funding constraints as the principle challenges to effective education. Overall, these findings indicate a strong demand for additional teaching resources, particularly interactive and application-oriented materials that support active learning and interdisciplinary education. This knowledge will support the development of an open educational resource (OER)-based interactive online educational platform, designed to enhance AMR education within a One Health context and support the training of future health professionals.