In vivo transcriptomes of Streptococcus suis reveal genes required for niche-specific adaptation and pathogenesis

Abstract

Streptococcus suis is a Gram-positive bacterium and a zoonotic pathogen residing in the nasopharynx or the gastrointestinal tract of pigs with a potential of causing life-threatening invasive disease. It is endemic in the porcine production industry worldwide, and it is also an emerging human pathogen. After invasion, the pathogen adapts to cause bacteremia and disseminates to different organs including the brain. To gain insights in this process, we infected piglets with a highly virulent strain of S. suis , and bacterial transcriptomes were obtained from blood and different organs (brain, joints, and heart) when animals had severe clinical symptoms of infection. Microarrays were used to determine the genome-wide transcriptional profile at different infection sites and during growth in standard growth medium in vitro . We observed differential expression of around 30% of the Open Reading Frames (ORFs) and infection-site specific patterns of gene expression. Genes with major changes in expression were involved in transcriptional regulation, metabolism, nutrient acquisition, stress defenses, and virulence, amongst others, and results were confirmed for a subset of selected genes using RT-qPCR. Mutants were generated in two selected genes, and the encoded proteins, i.e., NADH oxidase and MetQ, were shown to be important virulence factors in coinfection experiments and in vitro assays. The knowledge derived from this study regarding S. suis gene expression in vivo and identification of virulence factors is important for the development of novel diagnostic and therapeutic strategies to control S. suis disease.

PmtA functions as a ferrous iron and cobalt efflux pump in Streptococcus suis

“…Our results clearly showed that PmtA does not affect the virulence of S. suis in mice. Consistent with this result, Arenas et al recently demonstrated that pmtA (SSU0288) is downregulated at all sites of infection and plays no major role in S. suis survival within the host using the piglet infection model [45]. Based on these observations, it is conceivable that the host may not employ iron toxicity to control bacterial infections.…”

Identification of conditionally essential genes for Streptococcus suis infection in pigs

“…Based on these results, we conclude that S. suis uses a balanced network of regulators to control metabolic adaptation and stress responses during infection. In our previous work, we showed that metabolic adaptation of S. suis to the different sites of infection is causing large changes in gene expression [21]. In this study, it is shown that these metabolic changes are not facultative, but essential for S. suis in order to survive in the harsh conditions of the host.…”

“…At the start of the experiment tonsil swabs of piglets were screened for the absence of S. suis serotype 2 isolates. After an acclimatization period of 3 days, piglets were infected intravenously with 10 6 CFU of strain 10 and coinfected with the same amount of one of the isogenic mutants as previously described [21]. After infection, blood was extracted at a daily base to allow white blood cell counting, and piglets were observed for clinical symptoms and behavior three times a day at 8 h intervals.…”

Quantitative proteomics revealed modulation of macrophages by MetQ gene of Streptococcus suis serotype 2

“…There may be a second methionine uptake system similar to the BcaP system of Lactococcus lactis to obtain methionine from the environment (den Hengst et al 2006 ; Basavanna et al 2013 ). Methionine synthesis and transport genes were reported to be related to the virulence of Brucella melitensis , Salmonella enterica and Streptococcus suis (Lestrate et al 2000 ; Ejim et al 2004 ; Arenas et al 2019 ).…”