Biology subjects

Gottschalk, M.

Publications and source records attributed to Gottschalk, M..

3 recordsLinked to original sources

bioRxiv2020

Capsular polysaccharide switching in Streptococcus suis modulates host cell interactions and virulence

Streptococcus suis serotype 2 strains can cause severe infections in both swine and humans. The capsular polysaccharide (CPS) of S. suis defines various serotypes based on its composition and structure. Though serotype switching from serotype 2 has been suggested to occur between S. suis strains, its impact on pathogenicity and virulence remains unknown. Herein, we experimentally generated S. suis serotype-switched mutants from a serotype 2 strain (SS2) that express the serotype 3, 4, 7, 8, 9, or 14 CPS (SS2to3, SS2to4, SS2to7, SS2to8, SS2to9, and SS2to14, respectively). The effects of serotype switching were then investigated with regards to classical properties conferred by presence of the serotype 2 CPS, including adhesion to/invasion of porcine tracheal epithelial cells, resistance to phagocytosis by murine macrophages, killing by murine and porcine whole blood, and dendritic cell-derived pro-inflammatory mediator production. Results demonstrated that these properties on host cell interactions were differentially modulated depending on the switched serotypes. Using a mouse model of systemic infection, SS2to8 was demonstrated to be hyper-virulent, with animals rapidly succumbing to septic shock, whereas SS2to3 and SS2to4 were less virulent than SS2 because of a reduced systemic inflammatory host response. By contrast, switching to serotype 7, 9, or 14 CPSs had little to no effect. Finally, development of clinical signs in a porcine model of infection was only observed following infection with SS2, SS2to7, and SS2to8. Taken together, these findings suggest that serotype switching can differentially modulate S. suis host cell interactions and virulence depending on the CPS type expressed. ImportanceStreptococcus suis serotype 2 is the most frequently type associated with swine and zoonotic infections. While the serotype 2 CPS is required for virulence and pathogenesis, little information is available regarding that of other serotypes and how differences in serotype can directly affect host cell interactions and virulence. Herein, we constructed serotype-switched mutants from a serotype 2 strain and demonstrated that serotype switching can shift and modulate the S. suis host cell interactions and virulence in vivo. Among the serotype-switched mutants, the mutant expressing the serotype 8 CPS, whose composition and structure are identical to that of the human pathogen Streptococcus pneumoniae serotype 19F, was hyper-virulent, whereas mutants expressing the serotype 3 or 4 CPSs had reduced virulence. These results demonstrate that serotype switching can drastically alter S. suis phenotype. Consequently, further importance and attention should be given to the phenomenon of serotype switching and the possible emergence of hyper-virulent isolates.

microbiology↗

bioRxiv2020

Genome reduction is associated with bacterial pathogenicity across different scales of temporal and ecological divergence

Emerging bacterial pathogens threaten global health and food security, and so it is important to ask whether these transitions to pathogenicity have any common features. We present a systematic study of the claim that pathogenicity is associated with genome reduction and gene loss. We compare broad-scale patterns across all bacteria, with detailed analyses of Streptococcus suis, a zoonotic pathogen of pigs, which has undergone multiple transitions between disease and carriage forms. We find that pathogenicity is consistently associated with reduced genome size across three scales of divergence (between species within genera, and between and within genetic clusters of S. suis). While genome reduction is most often associated with bacterial endosymbionts, other correlates of symbiosis (reduced metabolic capacity, GC content, and the expansion of non-coding elements) are not found consistently in pathogens, and genome reduction in pathogens cannot be attributed to changes in intracellularity or host restriction. Together, our results indicate that genome reduction is a predictive marker of pathogenicity in bacteria, and that the causes and consequences of genome reduction in pathogens are sometimes distinct from those in endosymbionts.

evolutionary biology↗

bioRxiv2020

Linking phenotype, genotype and ecology: antimicrobial resistance in the zoonotic pathogen Streptococcus suis

Antimicrobial resistance (AMR) is among the gravest threats to human health and food security worldwide. Pigs receive more antimicrobials than most other livestock, and are a known source of zoonotic disease. We studied AMR in Streptococcus suis, a commensal found in most pigs, but which can also cause serious disease in both pigs and humans. We obtained replicated measures of Minimum Inhibitory Concentration (MIC) for 16 antibiotics, across a panel of 678 isolates, from the major pig-producing regions of the world. For several drugs, there was no natural separation into "resistant" and "susceptible", highlighting the need to treat MIC as a quantitative trait. We found differences in MICs between countries, consistent with their patterns of antimicrobial usage. AMR levels were high even for drugs not used to treat S. suis, with many multi-drug resistant isolates. And similar levels of resistance were found in pigs and humans from zoonotic regions. We next used whole genome sequences for each isolate to identify 43 candidate resistance determinants, 22 of which were novel in S. suis. The presence of these determinants explained most of the variation in MIC. But there were also complications, including epistatic interactions, where known resistance alleles had no effect in some genetic backgrounds. Beta-lactam resistance involved many variants of small effect, appearing in a characteristic order. Our results confirm the potential for genomic data to aid in the fight against AMR, but also demonstrate that it cannot be tackled one species or one drug at a time.

microbiology↗