lipoteichoic-acid and Pneumococcal-Infections

Topics: Animals; Humans; Lipopolysaccharides; Pneumococcal Infections; Streptococcus pneumoniae; Teichoic Acids

Host-to-host transmission is a necessary but poorly understood aspect of microbial pathogenesis. Herein, we screened a genomic library of mutants of the leading respiratory pathogen

Topics: Alanine; Animals; Animals, Newborn; Bacterial Proteins; Bacterial Shedding; Disease Models, Animal; DNA Transposable Elements; Genomic Library; Host-Pathogen Interactions; Inflammation; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mutagenesis; Pneumococcal Infections; Respiratory System; Streptococcus pneumoniae; Teichoic Acids

Pneumococcal asymptomatic colonization of the respiratory tracts is a major risk for invasive pneumococcal disease. We have previously shown that pneumococcal wall teichoic acid (WTA) was involved in pneumococcal infection of sepsis and adherence to epithelial and endothelial cells. In this study, we investigated the contribution of pneumococcal WTA to bacterial colonization and dissemination in murine models. The result showed that nasopharynx colonizing D39 bacterial cells have a distinct phenotype showing an increased exposure of teichoic acids relative to medium-grown bacteria. The WTA-deficient mutants were impaired in their colonization to the nasopharynx and lungs, and led to a mild inflammation in the lungs at 36 h post-inoculation. Pretreatment of the murine nares with WTA reduced the ability of wild type D39 bacteria to colonize the nasopharynx. In addition, the WTA-deficient strain was impaired in its ability to invade the blood and brain following intranasal administration. WTA-deficient D39 strain was reduced in C3 deposition but was more susceptible to the killing by the neutrophils as compared with its parent strain. Our results also demonstrated that the WTA enhanced pneumococcal colonization and dissemination independently of the host strains. These results indicate that WTA plays an important role in pneumococcal pathogenesis, both in colonization and dissemination processes.

Topics: Animals; Bacterial Proteins; Complement C3; Disease Models, Animal; Female; Flow Cytometry; Lipopolysaccharides; Lung; Mice; Mice, Inbred BALB C; Mutation; Nasopharynx; Phenotype; Pneumococcal Infections; Streptococcus pneumoniae; Teichoic Acids; Virulence

We used a rabbit model to assess the effects of capsular serotype, genetic background and beta-lactam resistance on the course and severity of experimental meningitis. Meningitis was induced by five pneumococcal strains belonging to five different clones with known invasive potential: two serotype 3 strains (ST260(3) and Netherlands(3)-31 clones) and three serotype 23F strains with different beta-lactam susceptibility patterns (Spain(23F)-1 clone, Tennessee(23F)-4 clone and a double locus variant of the Tennessee(23F)-4 clone). Major differences in secondary bacteremia and mortality rates were observed between serotypes 3 and 23F, as were divergences in the CSF lactate, protein and lipoteichoic-teichoic acid concentrations. Minor differences in the CSF-induced inflammatory response were found among strains belonging to the same serotype. Our results suggest that capsular serotype might be the main factor determining the course and severity of pneumococcal meningitis and genetic background contributes to a lesser extent. The acquisition of beta-lactam resistance does not reduce the virulence of the invasive clones. Since five strains belonging to two serotypes were studied, our findings have to be confirmed with other pneumococcal serotypes.

Topics: Adult; Animals; Bacteremia; Bacterial Capsules; beta-Lactam Resistance; Blood; Cerebrospinal Fluid; Colony Count, Microbial; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Infant; Lactic Acid; Lipopolysaccharides; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Pneumococcal Infections; Proteins; Rabbits; Serotyping; Streptococcus pneumoniae; Teichoic Acids; Virulence

Experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), can be aggravated by a mild Streptococcus pneumoniae infection. This study was performed to assess whether treatment with antibiotics inhibiting bacterial protein synthesis reduces the detrimental effect of infection on the course of EAE.. In vitro, release of proinflammatory pneumococcal products was studied by enzyme immunoassay and western blot. Seven days after induction of EAE (prior to the onset of symptoms) mice were infected intraperitoneally with S. pneumoniae and treated either with the inhibitors of bacterial protein synthesis minocycline or rifampicin, or with the beta-lactam ceftriaxone.. During bacterial killing in vitro, minocycline and rifampicin released lower quantities of proinflammatory bacterial products from S. pneumoniae than ceftriaxone. Mice treated with minocycline developed symptoms of EAE 1 day later than mice treated with ceftriaxone. Neither minocycline nor rifampicin therapy, however, reduced the severity of EAE in comparison with ceftriaxone treatment.. Although statistically significant (P = 0.04), a delay of 1 day in the onset of symptoms of EAE after minocycline treatment is of minor clinical relevance. These data do not support the hypothesis of superiority of a bacterial protein synthesis inhibitor over a beta-lactam antibiotic for the treatment of concomitant infections during the latent phase of EAE or MS.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Encephalomyelitis, Autoimmune, Experimental; Female; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Minocycline; Pneumococcal Infections; Rifampin; Teichoic Acids

Streptococcus pneumoniae and Haemophilus influenzae are human pathogens that often asymptomatically colonize the mucosal surface of the upper respiratory tract, but also occasionally cause invasive disease. The ability of these species to traverse the epithelium of the airway mucosa was modeled in vitro using polarized respiratory epithelial cells in culture. Migration across the epithelial barrier was preceded by loss of transepithelial resistance. Membrane products of S. pneumoniae that included lipoteichoic acid induced disruption of the epithelial barrier in a Toll-like receptor 2-dependent manner. This result correlates with a recent genetic study that associates increased TLR2 signaling with increased rates of invasive pneumococcal disease in humans. Loss of transepithelial resistance by the TLR2 ligand correlated with activation of p38 MAP kinase and transforming growth factor (TGF)-beta signaling. Activation of p38 MAPK and TGF-beta signaling in epithelial cells upon nasal infection with S. pneumoniae was also demonstrated in vivo. Inhibition of either p38 MAPK or TGF-beta signaling was sufficient to inhibit the migration of S. pneumoniae or H. influenzae. Our data shows that diverse bacteria utilize common mechanisms, including MAPK and TGF-beta signaling pathways to disrupt epithelial barriers and promote invasion.

Topics: Animals; Caco-2 Cells; Cell Membrane; Cell Polarity; Epithelial Cells; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Lipopolysaccharides; MAP Kinase Signaling System; Mice; Models, Biological; p38 Mitogen-Activated Protein Kinases; Pneumococcal Infections; Respiratory Mucosa; Streptococcus pneumoniae; Teichoic Acids; Toll-Like Receptor 2; Transforming Growth Factor beta

Production and release of the pneumococcal virulence factors pneumolysin and lipoteichoic and teichoic acid in 75 clinical isolates were investigated. No difference was found between strains causing systemic infection or localized respiratory infection and isolates from asymptomatic carriers. This suggests that the presence of pneumolysin and lipoteichoic and teichoic acid is a necessary but not a sufficient condition for pneumococcal infection and development of invasive disease.

Topics: Bacterial Proteins; Humans; Lipopolysaccharides; Pneumococcal Infections; Streptolysins; Teichoic Acids