Muramidase-released protein (MRP) is as an important virulence marker of Streptococcus suis (S. suis) serotype 2. Our previous works have shown that MRP can bind human fibrinogen (hFg); however, the function of this interaction in S. suis meningitis is not known. In this study, we found that the deletion of mrp significantly impairs the hFg-mediated adherence and traversal ability of S. suis across human cerebral microvascular endothelial cells (hCMEC/D3). Measurement of the permeability to Lucifer yellow in vitro and Evans blue extravasation in vivo show that the MRP-hFg interaction significantly increases the permeability of the blood–brain barrier (BBB). In the mouse meningitis model, wild type S. suis caused higher bacterial loads in the brain and more severe histopathological signs of meningitis than the mrp mutant at day 3 post-infection. Western blot analysis and immunofluorescence observations reveal that the MRP-hFg interaction can destroy the cell adherens junction protein p120-catenin of hCMEC/D3. These results indicate that the MRP-hFg interaction is important in the development of S. suis meningitis.

Streptococcus suis serotype 2 is a crucial pathogenic cause of bacterial meningitis, a life-threatening disease with neurological sequelae and high rates of mortality. Inflammation triggered by S. suis infection must be precisely regulated to prevent further tissue damage. As a glucocorticoid anti-inflammatory mediator, annexin A1 (AnxA1) mainly acts through formyl peptide receptor 2 (Fpr2) to alleviate inflammation in the peripheral system. In this study, we evaluated the roles of AnxA1 and Fpr2 in a mouse model of S. suis meningitis created via intracisternal infection in Fpr2-deficient (Fpr2^−/−) and wild-type (WT) mice. We revealed that Fpr2^−/− mice were highly susceptible to S. suis meningitis, displaying increased inflammatory cytokine levels, bacterial dissemination, and neutrophil migration compared with WT mice. Additionally, AnxA1 exerted anti-inflammatory effects through Fpr2, such as attenuation of leukocyte infiltration, inflammatory mediator production, and astrocyte or microglial activation in the brain. Importantly, we found that the antimigratory function of AnxA1 decreases neutrophil adherence to the endothelium through Fpr2. Finally, an in vitro study revealed that AnxA1 potentially suppresses interleukin-6 (IL-6) expression through the Fpr2/p38/COX-2 pathway. These data demonstrated that Fpr2 is an anti-inflammatory receptor that regulates neutrophil migration in mice with S. suis meningitis and identified AnxA1 as a potential therapeutic option.

Bacterial meningitis remains a substantial cause of mortality worldwide and survivors may have severe lifelong disability. Although we know that meningeal bacterial pathogens must cross blood-central nervous system (CNS) barriers, the mechanisms which facilitate the virulence of these pathogens are poorly understood. Here, we show that adenosine from a surface enzyme (Ssads) of Streptococcus suis facilitates this pathogen’s entry into mouse brains. Monolayer translocation assays (from the human cerebrovascular endothelium) and experiments using diverse inhibitors and agonists together demonstrate that activation of the A1 adenosine receptor signaling cascade in hosts, as well as attendant cytoskeleton remodeling, promote S. suis penetration across blood-CNS barriers. Importantly, our additional findings showing that Ssads orthologs from other bacterial species also promote their translocation across barriers suggest that exploitation of A1 AR signaling may be a general mechanism of bacterial virulence.

Is an opportunistic pathogen that can cause emetic or diarrheal foodborne illness. Previous studies have identified multiple pathogenic B. cereus strains and characterized a variety of virulence fa...

Serious diseases caused by Streptococcus suis serotype 2 (S. suis 2) include septicaemia and meningitis, which are associated with high morbidity and mortality. Proliferation in the blood can result in a breach of the blood–brain barrier (BBB) and provide entry into the cerebrospinal fluid (CSF), where bacteria cause inflammation of the meningeal membranes resulting in meningitis. The molecular mechanisms of how this pathogen crosses the BBB remain unclear. Suilysin (SLY) has been identified as an important secreted virulence factor of S. suis 2 and may play a vital role in provoking meningitis. In this investigation, we demonstrate that SLY can increase the paracellular permeability of BBB, both in vivo and in vitro, via the activation of group III secretory phospholipase A2 (PLA2G3). Our results indicate that at lower, sublytic concentrations, the toxin can stimulate cerebral microvascular endothelial cells to release TNF-α, thereby inducing high level expressions of PLA2G3. Abnormal elevations of PLA2G3 might further injure tissues through direct cytolytic effectors or other responses.

Background: Respiratory infections are a serious threat to human health. So, rapid detection of all respiratory pathogens can facilitate prompt treatment and prevent the deterioration of respiratory disease. Previously published primers and probes of the TaqMan array card (TAC) for respiratory pathogens are not sensitive to Chinese clinical specimens. This study aimed to develop and improve the TAC assay to detect 28 respiratory viral and bacterial pathogens in a Chinese population. Methods: To improve the sensitivity, we redesigned the primers and probes, and labeled the probes with minor groove binders. The amplification efficiency, sensitivity, and specificity of the primers and probes were determined using target-gene containing standard plasmids. The detection performance of the TAC was evaluated on 754 clinical specimens and the results were compared with those from conventional methods. Results: The performance of the TAC assay was evaluated using 754 clinical throat swab samples and the results were compared with those from gold-standard methods. The sensitivity and specificity were 95.4 and 96.6%, respectively. The lowest detection limit of the TAC was 10 to 100 copies/μL. Conclusions: TAC is an efficient, accurate, and high-throughput approach to detecting multiple respiratory pathogens simultaneously and is a promising tool for the identification of pathogen outbreaks.