Streptococcus suis is a swine pathogen and a zoonotic agent afflicting people in close contact with infected pigs or pork meat. Sporadic cases of human infections have been reported worldwide. In addition, S. suis outbreaks emerged in Asia, making this bacterium a primary health concern in this part of the globe. In pigs, S. suis disease results in decreased performance and increased mortality, which have a significant economic impact on swine production worldwide. Facing the new regulations in preventive use of antimicrobials in livestock and lack of effective vaccines, control of S. suis infections is worrisome. Increasing and sharing of knowledge on this pathogen is of utmost importance. As such, the pathogenesis and epidemiology of the infection, antimicrobial resistance, progress on diagnosis, prevention, and control were among the topics discussed during the 4th International Workshop on Streptococcus suis (held in Montreal, Canada, June 2019). This review gathers together recent findings on this important pathogen from lectures performed by lead researchers from several countries including Australia, Canada, France, Germany, Japan, Spain, Thailand, The Netherlands, UK, and USA. Finally, policies and recommendations for the manufacture, quality control, and use of inactivated autogenous vaccines are addressed to advance this important field in veterinary medicine.

Proliferative enteropathy is an infectious disease caused by an obligate intracellular bacterium, Lawsonia intracellularis, and characterized by thickening of the intestinal epithelium due to enterocyte proliferation. The disease is endemic in swine herds and has been occasionally reported in various other species. Furthermore, outbreaks among foals began to be reported on breeding farms worldwide within the past 5 years. Cell proliferation is directly associated with bacterial infection and replication in the intestinal epithelium. As a result, mild to severe diarrhea is the major clinical sign described in infected animals. The dynamics of L. intracellularis infection in vitro and in vivo have been well characterized, but little is known about the genetic basis for the pathogenesis or ecology of this organism. The present review focuses on the recent advances regarding the pathogenesis and host-pathogen interaction of L. intracellularis infections.

Since 2007, outbreaks of severe bloody diarrhea and hemorrhagic colitis have been reported in the United States and Canada. Though the primary causative agent of swine dysentery is Brachyspira hyodysenteriae, which is strongly hemolytic, the current report describes the isolation of a novel strongly hemolytic Brachyspira sp. This novel Brachyspira sp. was identified from clinical submissions at the Minnesota Veterinary Diagnostic Laboratory, and 40 of such isolates were obtained from 22 clinical submissions representing 5 states. Isolates were confirmed to be different from any known Brachyspira sp. on the basis of phylogenetic analysis of nucleotide sequences of nox and 16S ribosomal RNA (rRNA) genes. Phylogenetic analyses grouped all isolates into 2 clades (clades I and II), and grouping patterns were similar for both nox and 16S rRNA gene sequence analyses. Phenotypically, all isolates were indole and hippurate negative, and enzymatic profiling indicated 2 types of profiles, irrespective of the phylogenetic grouping, differing only in the production of β-glucosidase. The results suggest that a potentially virulent new species of Brachyspira sp., provisionally named “Brachyspira hampsonii ”, is circulating among swine herds in the United States.

Lawsonia intracellularis is an obligate intracellular bacterium and the etiologic agent of proliferative enteropathy. The disease is endemic in pigs, emerging in horses and has been described in various other species including nonhuman primates. Cell proliferation is associated with bacterial replication in enterocyte cytoplasm, but the molecular basis of the host-pathogen interaction is unknown. We used laser capture microdissection coupled with RNA-seq technology to characterize the transcriptional responses of infected enterocytes and the host-pathogen interaction. Proliferative enterocytes was associated with activation of transcription, protein biosynthesis and genes acting on the G1 phase of the host cell cycle (Rho family). The lack of differentiation in infected enterocytes was demonstrated by the repression of membrane transporters related to nutrient acquisition. The activation of the copper uptake transporter by infected enterocytes was associated with high expression of the Zn/Cu superoxide dismutase by L. intracellularis. This suggests that the intracellular bacteria incorporate intracytoplasmic copper and express a sophisticated mechanism to cope with oxidative stress. The feasibility of coupling microdissection and RNA-seq was demonstrated by characterizing the host-bacterial interactions from a specific cell type in a heterogeneous tissue. High expression of L. intracellularis genes encoding hypothetical proteins and activation of host Rho genes infers the role of unrecognized bacterial cyclomodulins in the pathogenesis of proliferative enteropathy.

Swine dysentery (SD) is a mucohemorrhagic colitis of swine classically caused by infection with the intestinal spirochete Brachyspira hyodysenteriae . Since around 2007, cases of SD have occurred in North America associated with a different strongly beta-hemolytic spirochete that has been molecularly and phenotypically characterized and provisionally named “ Brachyspira hampsonii. ” Despite increasing international interest, B. hampsonii is currently not recognized as a valid species. To support its recognition, we sequenced the genomes of strains NSH-16 ^T , NSH-24, and P280/1, representing B. hampsonii genetic groups I, II, and III, respectively, and compared them with genomes of other valid Brachyspira species. The draft genome of strain NSH-16 ^T has a DNA G+C content of 27.4% and an approximate size of 3.2 Mb. Genomic indices, including digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI), and average amino acid identity (AAI), clearly differentiated B. hampsonii from other recognized Brachyspira species. Although discriminated genotypically, the three genetic groups are phenotypically similar. By electron microscopy, cells of different strains of B. hampsonii measure 5 to 10 μm by 0.28 to 0.34 μm, with one or two flat curves, and have 10 to 14 periplasmic flagella inserted at each cell end. Using a comprehensive evaluation of genotypic (gene comparisons and multilocus sequence typing and analysis), genomic (dDDH, ANI, and AAI) and phenotypic (hemolysis, biochemical profiles, protein spectra, antibiogram, and pathogenicity) properties, we classify Brachyspira hampsonii sp. nov. as a unique species with genetically diverse yet phenotypically similar genomovars (I, II, and III). We designate the type strain NSH-16 (= ATCC BAA-2463 = NCTC 13792).

Outbreaks of swine dysentery, caused by B. hyodysenteriae and the recently discovered “B. hampsonii”, have re-occurred in North American swine herds since the late 2000s. Additionally, multiple Brachyspira species have been increasingly isolated by North American diagnostic laboratories. In Europe, the reliance on antimicrobial therapy for control of swine dysentery has been followed by reports of antimicrobial resistance over time. The objective of our study was to determine the antimicrobial susceptibility trends of four Brachyspira species originating from US swine herds, and investigate their associations with the bacterial species, genotypes and epidemiological origins of the isolates. We evaluated the susceptibility of B. hyodysenteriae, “B. hampsonii”, B. pilosicoli and B. murdochii to tiamulin, valnemulin, doxycycline, lincomycin and tylosin by broth microdilution and to carbadox by agar dilution. In general, Brachyspira species showed high susceptibility to tiamulin, valnemulin and carbadox, heterogeneous susceptibility to doxycycline and low susceptibility to lincomycin and tylosin. A trend of decreasing antimicrobial susceptibility by species was observed (“B. hampsonii” > B. hyodysenteriae > B. murdochii > B. pilosicoli). In general, Brachyspira isolates from the US were more susceptible to these antimicrobials than isolates from other countries. Decreased antimicrobial susceptibility was associated with the genotype, stage of production and production system from which the isolate originated, thus highlighting the role of biosecurity and husbandry in disease prevention and control. Finally, this study also highlights the urgent need for Clinical Laboratory Standards Institute approved clinical breakpoints for Brachyspira species in order to facilitate informed therapeutic and control strategies.