The Streptococcus suis transcriptional landscape reveals adaptation mechanisms in pig blood and cerebrospinal fluid

Abstract

Streptococcus suis (SS) is an important pathogen of pigs, and it is also recognized as a zoonotic agent for humans. SS infection may result in septicemia or meningitis in the host. However, little is known about genes that contribute to the virulence process and survival within host blood or cerebrospinal fluid (CSF). Small RNAs (sRNA) have emerged as key regulators of virulence in several bacteria, but they have not been investigated in SS. Here, using a differential RNA-sequencing approach and RNAs from SS strain P1/7 grown in rich medium, pig blood, or CSF, we present the SS genome-wide map of 793 transcriptional start sites and 370 operons. In addition to identifying 29 sRNAs, we show that five sRNA deletion mutants attenuate SS virulence in a zebrafish infection model. Homology searches revealed that 10 sRNAs were predicted to be present in other pathogenic Streptococcus species. Compared with wild-type strain P1/7, sRNAs rss03, rss05, and rss06 deletion mutants were significantly more sensitive to killing by pig blood. It is possible that rss06 contributes to SS virulence by indirectly activating expression of SSU0308, a virulence gene encoding a zinc-binding lipoprotein. In blood, genes involved in the synthesis of capsular polysaccharide (CPS) and subversion of host defenses were up-regulated. In contrast, in CSF, genes for CPS synthesis were down-regulated. Our study is the first analysis of SS sRNAs involved in virulence and has both improved our understanding of SS pathogenesis and increased the number of sRNAs known to play definitive roles in bacterial virulence.

SCM, the M Protein of Streptococcus canis Binds Immunoglobulin G

“…However, capsule expression is a very dynamic process and can vary depending on environmental and stress conditions, such as nutrient availability or antibiotic treatments (Hammerschmidt et al, 2005; Willenborg et al, 2011; Haas and Grenier, 2016; Kietzman et al, 2016). Under nutrient-rich conditions, capsule expression is highly upregulated which is consistent with numerous studies characterizing the bacterial capsule as the main virulence factor of streptococci in the blood (Wu et al, 2014). In contrast, at tissue sites, where nutrient-availability is likely restricted, capsule expression is downregulated, leading to demasking of surface-anchored proteins which are otherwise hidden.…”

Streptococcus suis synthesizes deoxyadenosine and adenosine by 5’-nucleotidase to dampen host immune responses

“…Deletion of nt in WT strain GZ0565 was achieved by allelic replacement as previously described [25]. The primers used for constructing Δ nt are listed in Supplementary Table S3.…”

“…From our RNA-seq data on S. suis strain GZ0565 (unpublished data), there is no transcript at the genomic intergenic region between BFP66_RS05970 and BFP66_RS05975 where the gene nt could be inserted into. The complemented strain for nt was constructed according to our previous report [25]. A fragment of the genome between BFP66_RS05970 and BFP66_RS05975 was fused with nt and its promoter by overlap-extension PCR.…”

Transcriptomic Analysis Reveals Selective Metabolic Adaptation of Streptococcus suis to Porcine Blood and Cerebrospinal Fluid

“…However, how S. suis adapts its metabolic activity to host environments is largely unknown [7]. Adaptation of bacterial pathogens to changing environments is accompanied by alterations in metabolic gene expression [8,9,10,11,12,13]. Thus, the gene transcriptional levels under infection-related conditions can be used for a better understanding of S. suis pathogenicity.…”