g(m1)-ganglioside and Pneumonia--Bacterial

Pseudomonas aeruginosa is an opportunistic organism, which frequently colonizes the respiratory tract of patients with impaired host defence. In cystic fibrosis (CF) patients, this pathogen causes a progressive destructive bronchitis and bronchiolitis and is responsible for high mortality. Normal respiratory epithelium is protected against bacteria via mucus and mucociliary clearance. Alteration of mucociliary clearance and of glycosylation of mucins in CF facilitates the access of bacteria to the underlying airway epithelial cells. Intact respiratory epithelium does not bind P. aeruginosa, whereas injured respiratory epithelium is highly susceptible to P. aeruginosa adherence. We found that the high affinity of respiratory epithelium, from CF and non-CF sources, for P. aeruginosa, during the wound repair process is related to the apical expression of asialo ganglioside M1 (aGM1). The affinity of repairing respiratory epithelium for P. aeruginosa is time-dependent, and is related to transient apical expression of aGM1 at the surface of repairing respiratory epithelial cells. CF respiratory epithelial cells apically express more aGM1 residues with relation to an increased affinity for P. aeruginosa than non CF cells. High epithelial damage followed by repair represents a major cause of P. aeruginosa adherence to airway epithelium in cystic fibrosis. However, P. aerurignosa adherence and colonization are not restricted to cystic fibrosis disease and P. aeruginosa pneumonia may also occur in severely immunocompromised patients, suggesting that epithelial injury and decreased host-response favour the colonization of the airways by P. aeruginosa.

Topics: Bacterial Adhesion; Bronchiolitis; Bronchitis; Cystic Fibrosis; Disease Susceptibility; Epithelium; G(M1) Ganglioside; Gene Expression; Humans; Immunocompromised Host; Mucociliary Clearance; Mucus; Opportunistic Infections; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory System; Wound Healing

A 36-year-old woman presented acute polyradiculoneuropathy following Chlamydia pneumoniae infection. Although electrophysiologic studies were normal, clinical features were typical of Guillain-Barré syndrome (GBS). Anti-ganglioside GM1 antibodies were positive. Two other cases of GBS following Chlamydia pneumoniae infection have been reported, but no specific feature emerges. Outcome was good in our patient after intravenous globulin then antibiotic therapy. Our case supports the notion that Chlamydia pneumoniae infection can induce GBS. The association is probably underestimated.

Topics: Adult; Antibodies, Bacterial; Autoantibodies; Autoimmune Diseases; Chlamydophila Infections; Chlamydophila pneumoniae; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Mycoplasma pneumoniae; Pneumonia, Bacterial; Tetracyclines

Pseudomonas aeruginosa strains are opportunistic pathogens associated with infections in immunocompromised hosts and patients with cystic fibrosis. Like many other mucosal pathogens, P. aeruginosa cells express flagella which provide motility and chemotaxis toward preferred substrates but also provide a ligand for clearance by phagocytic cells. We tested the role of flagella in the initial stages of respiratory tract infection by comparing the virulence of fliC mutants in a neonatal mouse model of pneumonia. In the absence of fliC, there was no mortality, compared with 30% mortality attributed to the parental strain PAK or 15% mortality associated with infection due to a pilA mutant PAK/NP (P < 0.0001). The fliC mutants caused pneumonia in only 25% of the mice inoculated, regardless of whether there was expression of the pilus, whereas the parental strain was associated with an 80% rate of pneumonia. Histopathological studies demonstrated that the fliC mutants caused very focal inflammation and that the organisms did not spread through the lungs as seen in infection due to either PAK or PAK/NP. Purified flagellin elicited an intense inflammatory response in the mouse lung. 125I-labeled flagellin bound to the glycolipids GM1 and GD1a and to asialoGM1 in an in vitro binding assay. However, flagellin-mediated binding to epithelial gangliosides was a relatively unusual event, as quantified by binding assays of wild-type or fliC mutant organisms to CHO Lec-2 cells with membrane-incorporated GM1. Fla+ organisms but not fliC mutants were efficiently taken up by murine macrophages. P. aeruginosa flagella are important in the establishment of respiratory tract infection and may act as a tether in initial interactions with epithelial membranes. This function is offset by the contribution of flagella to host clearance mechanisms facilitating phagocytic clearance and the role of flagellar genes in mucin binding and clearance.

Topics: Animals; Bacterial Adhesion; Bacterial Proteins; CHO Cells; Cricetinae; DNA-Binding Proteins; Fimbriae Proteins; Flagella; Flagellin; Flow Cytometry; G(M1) Ganglioside; Gangliosides; Inflammation; Macrophages; Mice; Mice, Inbred BALB C; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Tumor Cells, Cultured; Virulence