Streptococcus suis capsular type 2 is an important swine pathogen and an agent of zoonosis. Although meningitis is the most common form of disease, septicemia and septic shock are also frequently reported. Despite reports that CD14 is involved in the recognition of encapsulated S. suis by host cells, the mechanisms underlying exacerbated release of pro-inflammatory cytokines, which may have a negative impact on disease outcome, are unclear. Here, we demonstrated that stimulation of human monocytes by whole encapsulated S. suis or its purified cell wall components influences the relative expression of Toll-like receptor (TLR)-2 and CD14 mRNA. Moreover, this stimulation triggered the release of cytokines (tumor necrosis factor-alpha, IL-1beta and IL-6) and chemokines (IL-8 and monocyte chemoattractant protein-1), which was significantly reduced by antibody-mediated blocking of TLR2 but not TLR4. Mouse macrophages deficient in TLR2 also showed impaired cytokine responses to encapsulated bacteria. Given that this response was completely abrogated in myeloid differentiation factor 88 (MyD88)-deficient macrophages, other TLRs might also be involved. Furthermore, we demonstrated that the presence of capsular polysaccharide (CPS)-modulated S. suis interactions with TLRs. In the absence of CPS, uncovered cell wall components induced cytokine and chemokine production via TLR2-dependent as well as -independent pathways, whereas CPS contributes to MCP-1 production in a MyD88-independent manner. Overall, this study contributes to a better understanding of the inflammatory processes induced by an encapsulated pathogen and suggests that the relative expression of CPS, known to be modulated during bacterial invasion and dissemination in the host, might alter interactions with host cells and, consequently, the outcome of the inflammatory response.

Bacillus cereus, Bacillus thuringiensis and Bacillus anthracis are closely related species that share a similar genetic background but occupy different ecological niches. Virulence plasmids bearing genes coding for toxins, may explain, at least partly, this specialization. We have compared by 2-DE in the early stationary phase of growth the extracellular proteomes of three strains of these species that have lost their virulence plasmids. Proteins expected to be secreted or to belong to the cell wall or to the cytosol were found in the three proteomes. For the cell wall and cytosolic proteins located in the extracellular space, the three proteomes were similar. Cytosolic proteins included enolase, GroEL, PdhB, PdhD, SodA and others. Cell surface proteins were mainly autolysins, proteases, nucleotidases and OppAs. In contrast, the secreted proteins profiles of B. cereus and B. thuringiensis were quite different from that of B. anthracis. B. cereus and B. thuringiensis extracellular proteomes both contained large amounts of secreted degradative enzymes and toxins, including nine proteases, three phospholipases, two haemolysins and several enterotoxins. Most of the genes encoding these enzymes and toxins are controlled by the transcriptional activator PlcR. The extracellular proteome of the pXO1-, pXO2- B. anthracis 9131 strain contained only one secreted protein: the metalloprotease InhA1, also found in the proteomes of the two other strains and possibly involved in antibacterial peptide degradation.

Acetylation is correlated with chromatin decondensation and transcriptional activation, but its regulation by histone deacetylase (HDAC)-bearing corepressor complexes is poorly understood. Here, we describe the mechanism of assembly of the mammalian Sin3L/Rpd3L complex facilitated by Sds3, a conserved subunit deemed critical for proper assembly. Sds3 engages a globular, helical region of the HDAC interaction domain (HID) of the scaffolding protein Sin3A through a bipartite motif comprising a helix and an adjacent extended segment. Sds3 dimerizes through not only one of the predicted coiled-coil motifs but also, the segment preceding it, forming an ∼150-Å-long antiparallel dimer. Contrary to previous findings in yeast, Sin3A rather than Sds3 functions in recruiting HDAC1 into the complex by engaging the latter through a highly conserved segment adjacent to the helical HID subdomain. In the resulting model for the ternary complex, the two copies of the HDACs are situated distally and dynamically because of a natively unstructured linker connecting the dimerization domain and the Sin3A interaction domain of Sds3; these features contrast with the static organization described previously for the NuRD (nucleosome remodeling and deacetylase) complex. The Sds3 linker features several conserved basic residues that could potentially maintain the complex on chromatin by nonspecific interactions with DNA after initial recruitment by sequence-specific DNA-binding repressors.transcription repression | histone deacetylase | corepressor complex | protein-protein interaction | structural biology H istone deacetylation constitutes the primary mechanism of erasing acetylation marks on histones, leading to a chromatin environment that is repressive to gene transcription. Histone deacetylases (HDACs) exhibit limited substrate specificity and rely on transcription factors with sequence-specific DNAbinding and/or chromatin-binding activities for their targeting specificity. Among 11 known Zn 2+ -dependent HDACs in mammals, only HDAC1, HDAC2, and HDAC3 are constitutively nuclear, regulating the transcription of a broad array of genes that impact fundamentally on cellular physiology and organism development (1-3). These HDACs are commonly found in multiprotein corepressor complexes, with the closely related HDAC1 and HDAC2 partitioning broadly into the Sin3L/Rpd3L, Sin3S/ Rpd3S, NuRD (nucleosome remodeling and deacetylase), and CoREST (corepressor of REST transcription factor) complexes, whereas HDAC3 is found exclusively in SMRT/NCoR (silencing mediator of retinoid and thyroid hormone receptor/nuclear receptor corepressor) complexes. Little is known regarding the structure and organization of these complexes, although molecular insights into HDAC recruitment into these complexes are beginning to emerge.High-resolution structures of HDAC1 and HDAC3 in complex with the MTA1 (metastatic tumor antigen 1) and SMRT subunits in the NuRD and SMRT/NCoR complexes, respectively (4, 5), revealed a shared structural theme involving the catalytic do...