muramidase and Haemophilus-Infections

Haemophilus parasuis is an opportunistic pathogen that causes Glässer's disease in swine, with polyserositis, meningitis, and arthritis. The high-temperature requirement A (HtrA)-like protease, which is involved in protein quality control, has been reported to be a virulence factor in many pathogens. In this study, we showed that HtrA of H. parasuis (HpHtrA) exhibited both chaperone and protease activities. Finally, nickel import ATP-binding protein (NikE), periplasmic dipeptide transport protein (DppA), and outer membrane protein A (OmpA) were identified as proteolytic substrates for HpHtrA. The protease activity reached its maximum at 40°C in a time-dependent manner. Disruption of the htrA gene from strain SC1401 affected tolerance to temperature stress and resistance to complement-mediated killing. Furthermore, increased autoagglutination and biofilm formation were detected in the htrA mutant. In addition, the htrA mutant was significantly attenuated in virulence in the murine model of infection. Together, these data demonstrate that HpHtrA plays an important role in the virulence of H. parasuis.

Topics: Amino Acid Sequence; Animals; Bacterial Proteins; Biofilms; Complement Activation; Disease Models, Animal; Genetic Complementation Test; Haemophilus Infections; Haemophilus parasuis; Mice; Molecular Chaperones; Muramidase; Mutation; Proteolysis; Recombinant Fusion Proteins; Stress, Physiological; Substrate Specificity; Virulence; Virulence Factors

Pathogenic bacteria colonize the airways of 30% to 40% of patients with COPD and cause approximately 50% of exacerbations. New strains of nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis are associated with exacerbations. Antimicrobial protein/peptides (AMPs) play important roles in innate lung defense against pathogens. To our knowledge, the changes in AMP baseline levels in respiratory secretions during bacterial colonization and exacerbation have not been described. The objective of this study was to elucidate the effects of the acquisition of a new strain of pathogenic bacteria on the airway levels of AMPs in patients with COPD.. One hundred fifty-three samples from 11 patients were selected from COPD sputum samples collected prospectively over 6 years. Samples were grouped as culture-negative (no pathogenic bacteria), colonization, and exacerbation due to new strains of NTHI and M catarrhalis. Levels of lysozyme, lactoferrin, LL-37, and secretory leukocyte protease inhibitor (SLPI) were measured by enzyme-linked immunosorbent assay and compared among groups by paired analysis.. Compared with baseline, sputum lysozyme levels were significantly lower during colonization and exacerbation by NTHI (P = .001 and P = .013, respectively) and M catarrhalis (P = .007 and P = .018, respectively); SLPI levels were lower with exacerbation due to NTHI and M catarrhalis (P = .002 and P = .004, respectively), and during colonization by M catarrhalis (P = 032). Lactoferrin levels did not change significantly; LL-37 levels were higher during exacerbation by NTHI and M catarrhalis (P = .001 and P = .018, respectively).. Acquisition of NTHI and M catarrhalis is associated with significant changes in airway levels of AMPs, with larger changes in exacerbation. Airway AMP levels are likely to be important in pathogen clearance and clinical outcomes of infection in COPD.

Topics: Aged; Aged, 80 and over; Antimicrobial Cationic Peptides; beta-Defensins; Cathelicidins; Disease Progression; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Inflammation; Lactoferrin; Male; Middle Aged; Moraxella catarrhalis; Moraxellaceae Infections; Muramidase; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Secretory Leukocyte Peptidase Inhibitor; Sputum

N-acetylmuramyl-L-alanine amidase (NAMLAA) specifically degrades peptidoglycan, a major component of bacterial cell walls. Lysozyme degrades peptidoglycan differently by hydrolyzing the aminosugar backbone of peptidoglycan. In another study, it was shown that the two enzymes act synergistically to inactivate the inflammatory properties of peptidoglycan. The presence of lysozyme and NAMLAA was determined in serum and cerebrospinal fluid (CSF) of patients with bacterial meningitis. High concentrations of lysozyme were found in CSF while, surprisingly, NAMLAA was not present. To explain this phenomenon, the degranulation pattern of neutrophils in CSF was compared with that of neutrophils from blood. Specific granules contain lysozyme and the azurophil granules contain both lysozyme and NAMLAA. CD66b expression on the cell surface, indicative for fusion of the specific granules with the cell membrane, was higher in CSF than in blood, while the marker for the azurophil granules was lower.

Topics: Adolescent; Adult; Aged; Antigens, CD; Antigens, Neoplasm; Cell Adhesion Molecules; Cell Degranulation; Cell Membrane; Child; Child, Preschool; Female; Flow Cytometry; GPI-Linked Proteins; Haemophilus Infections; Humans; Infant; Male; Membrane Glycoproteins; Meningitis, Bacterial; Meningitis, Meningococcal; Middle Aged; Muramidase; N-Acetylmuramoyl-L-alanine Amidase; Neutrophil Activation; Neutrophils; Pneumococcal Infections

The ocular findings in three brothers with Bruton's disease are reported. All three boys had purulent conjunctivitis, but the two older brothers also developed marked corneal scarring with visual impairment. Haemophilus influenzae was cultured from conjunctival swabs; it was resistant to neomycin but sensitive to chloramphenicol. Tear analysis showed that the three subjects had normal levels of lysozyme but no detectable IgA.

Topics: Agammaglobulinemia; Child; Chloramphenicol; Conjunctivitis, Bacterial; Corneal Diseases; Haemophilus Infections; Humans; Immunoglobulins; Infant; Male; Muramidase; Secretory Component; Tears

Topics: Adult; Antibodies; Blood Bactericidal Activity; Calcium; Chlorides; Complement System Proteins; Escherichia; Escherichia coli; Ethanol; Haemophilus Infections; Humans; Magnesium; Male; Muramidase; Potassium; Sodium; Time Factors