Auger, J.-P. | Search bioRxiv

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

Pain burden, sensory profile and inflammatory cytokines of dogs with naturally-occurring neuropathic pain treated with gabapentin alone or with meloxicam

Canine neuropathic pain (NeuP) has been poorly investigated. This study aimed to evaluate the pain burden, sensory profile and inflammatory cytokines in dogs with naturally-occurring NeuP. Twenty-nine client-owned dogs with NeuP were included in a prospective, partially masked, randomized crossover clinical trial, and treated with gabapentin/placebo/gabapentin-meloxicam or gabapentin-meloxicam/placebo/gabapentin (each treatment block of 7 days; total 21 days). Pain scores, mechanical (MNT) and electrical (ENT) nociceptive thresholds and descending noxious inhibitory controls (DNIC) were assessed at baseline, days 7, 14, and 21. DNIC was evaluated using {Delta}MNT (after-before conditioning stimulus). Positive or negative {Delta}MNT corresponded to inhibitory or facilitatory pain profiles, respectively. Data from baseline were compared to those of sixteen healthy controls. {Delta}MNT, but not MNT and ENT, was significantly larger in controls (2.3 {+/-} 0.9 N) than in NeuP (-0.2 {+/-} 0.7 N). The percentage of dogs with facilitatory sensory profile was similar at baseline and after placebo (61.5-63%), and between controls and after gabapentin (33.3-34.6%). Pain scores were lower than baseline after gabapentin or gabapentin-meloxicam. Cytokine levels were not different between groups or treatments. Dogs with NeuP have deficient inhibitory pain mechanisms. Pain burden was reduced after gabapentin and gabapentin-meloxicam depending on the pain scoring instrument used.

neuroscience↗