Transcriptome and metabolome profiling to elucidate the mechanism underlying the poor growth of Streptococcus suis serotype 2 after orphan response regulator CovR deletion
Ontology highlight
ABSTRACT:
SUBMITTER: Zong B
PROVIDER: S-EPMC10661955 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Streptococcus suis serotype 2 is an emerging zoonotic pathogen responsible for a wide range of life-threatening diseases in pigs and humans. However, the pathogenesis of S. suis serotype 2 infection is not well understood. In this study, we report that an orphan response regulator, CovR, globally regulates gene expression and negatively controls the virulence of S. suis 05ZYH33, a streptococcal toxic shock syndrome (STSS)-causing strain. A covR-defective (DeltacovR) mutant of 05ZYH33 displayed dramatic phenotypic changes, such as formation of longer chains, production of thicker capsules, and increased hemolytic activity. Adherence of the DeltacovR mutant to epithelial cells was greatly increased, and its resistance to phagocytosis and killing by neutrophils and monocytes was also significantly enhanced. More importantly, inactivation of covR increased the lethality of S. suis serotype 2 in experimental infection of piglets, and this phenotype was restored by covR complementation. Colonization experiments also showed that the DeltacovR mutant exhibited an increased ability to colonize susceptible tissues of piglets. The pleiotropic phenotype of the DeltacovR mutant is in full agreement with the large number of genes controlled by CovR as revealed by transcription profile analysis: 2 genes are positively regulated, and 193 are repressed, including many that encode known or putative virulence factors. These findings suggested that CovR is a global repressor in virulence regulation of STSS-causing S. suis serotype 2.
| S-EPMC2668425 | biostudies-literature
Project description:BackgroundStreptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen. Orphan response regulator CovR plays crucial regulative functions in the survivability and pathogenicity of S. suis 2. However, research on the CovR in S. suis 2 is limited.ResultsIn this study, the regulative functions of CovR in the survivability and pathogenicity were investigated in S. suis 2 isolated from a diseased pig. The deletion of CovR significantly weakened the survivability and pathogenicity of S. suis 2. Compared with the wild-type strain, ΔcovR showed slower growth rates and thinner capsular polysaccharides. Moreover, ΔcovR showed reduced adhesion and invasion to Hep-2 cells as well as anti-phagocytosis and anti-killing ability to 3D4 cells and anti-serum killing ability. In addition, the deletion of CovR significantly reduced the colonisation ability of S. suis 2 in mice. The survival rate of mice infected with ΔcovR was increased by 16.7% compared with that of mice infected with S. suis 2. Further, the deletion of CovR led to dramatic changes in metabolism-related pathways in S. suis 2, five of those, including fructose and mannose metabolism, glycerolipid metabolism, ABC transporters, amino sugar and nucleotide sugar metabolism and phosphotransferase system, were significantly down-regulated.ConclusionsBased on the results, CovR plays positive regulative functions in the survivability and pathogenicity of S. suis 2 SC19 strain isolated from a pig.
| S-EPMC10664645 | biostudies-literature
Project description:Many Streptococcus suis isolates from porcine endocarditis in slaughterhouses have lost their capsule and are considered avirulent. However, we retrieved capsule- and virulence-recovered S. suis after in vivo passages of a nonencapsulated strain in mice, suggesting that nonencapsulated S. suis are still potentially hazardous for persons in the swine industry.
| S-EPMC5038428 | biostudies-literature
Project description:Streptococcus suis serotype 2 (SS2), an important zoonotic agent, is notorious for causing contagious porcine diseases and human infection. The two outbreaks in China (in 1998 and in 2005) have caused serious economic losses in the pig industry and posed public health for its new toxin shock symptoms (TSS). However, the molecular mechanism of SS2 pathogenicity is still poorly understood. In order to get insights into pathogenecity of SS2, eighteen SS2 strains of different virulence and sources have been subjected to whole genome comparison by NimbleGen CGS arrays
2009-08-29 | GSE17868 | GEO
Project description:BackgroundStreptococcus suis serotype 2 (S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure.Methods and findingsWe investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks.ConclusionsWe report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study.
| S-EPMC1434494 | biostudies-literature
Project description:A secreted nuclease, SsnA, was identified in the virulent Streptococcus suis isolate SX332 and subsequently in each of the type strains of capsular serotypes 1 through 9. Screening of 258 porcine clinical isolates from surface (nasal mucosa or palatine tonsil) or internal (joint, brain or other internal organ) locations revealed a significant relationship (P < 0.001) between expression of nuclease and isolation from an internal site. A 3,126-bp gene, ssnA, was identified from a phenotypically nuclease-negative pGh9:ISS1 insertion mutant, and analysis of the predicted SsnA sequence revealed a 35-amino-acid (aa) secretion signal sequence, a 22-aa DNA-binding domain, and a typical gram-positive cell wall sorting motif. A requirement of Ca2+ and Mg2+ for SsnA activity was determined, and the substrate specificity was found to be for single- and double-stranded linear DNA. Reverse transcription-PCR experiments revealed that ssnA is expressed throughout all stages of S. suis growth, and Western blots with porcine anti-S. suis immune sera against a recombinant, truncated SsnA derivative (rSsnADelta) confirmed that SsnA is expressed in vivo. Furthermore, anti-rSsnADelta antibodies were sufficient to neutralize SsnA activity. Analyses of subcellular fractions of SX332 and derived mutants, on DNA-containing polyacrylamide gels and by Western blotting, suggest that SsnA is cell wall located.
| S-EPMC321577 | biostudies-literature
Project description:We report here the first complete genome sequence of Streptococcus suis serotype 16, which has been identified to be zoonotic. The sequenced strain TL13 was isolated from a pig in China. The genome is 2,038,146 bp in length, covering 1,950 coding sequences, 53 tRNAs, and 4 rRNA loci.
| S-EPMC3695429 | biostudies-literature
Project description:Streptococcus suis is an important zoonotic agent leading to a variety of diseases in swine and can be transmitted to human beings upon close contact. Here, we report the complete genome sequence of S. suis serotype 14 strain JS14 which was isolated from a diseased pig in Jiangsu Province, China.
| S-EPMC3133069 | biostudies-literature
Project description:Streptococcus suis is a zoonotic pathogen causing economic loss in the swine industry and is also a threat to human health. To date, the mechanism of pathogenesis is not fully understood. Here, we report the complete genome sequence of S. suis strain ST3 of serotype 3, which provides opportunities to reveal genetic basis of infection of S. suis non-serotype 2 strains.
| S-EPMC3133292 | biostudies-literature
Project description:Streptococcus suis is a swine pathogen and zoonotic agent responsible for meningitis and septic shock. Although several putative virulence factors have been described, the initial steps of the S. suis pathogenesis remain poorly understood. While controversial results have been reported for a S. suis serotype 2 zinc metalloprotease (Zmp) regarding its IgA protease activity, recent phylogenetic analyses suggested that this protein is homologous to the ZmpC of Streptococcus pneumoniae, which is not an IgA protease. Based on the previously described functions of metalloproteases (including IgA protease and ZmpC), different experiments were carried out to study the activities of that of S. suis serotype 2. First, results showed that S. suis, as well as the recombinant Zmp, were unable to cleave human IgA1, confirming lack of IgA protease activity. Similarly, S. suis was unable to cleave P-selectin glycoprotein ligand-1 and to activate matrix metalloprotease 9, at least under the conditions tested. However, S. suis was able to partially cleave mucin 16 and syndecan-1 ectodomains. Experiments carried out with an isogenic Δzmp mutant showed that the Zmp protein was partially involved in such activities. The absence of a functional Zmp protein did not affect the ability of S. suis to adhere to porcine bronchial epithelial cells in vitro, or to colonize the upper respiratory tract of pigs in vivo. Taken together, our results show that S. suis serotype 2 Zmp is not a critical virulence factor and highlight the importance of independently confirming results on S. suis virulence by different teams.
| S-EPMC6206940 | biostudies-literature