Lysozyme is an abundant, cationic antimicrobial protein that plays an important role in pulmonary host defense. Increased concentration of lysozyme in the airspaces of transgenic mice enhanced bacterial killing whereas lysozyme deficiency resulted in increased bacterial burden and morbidity. Lysozyme degrades peptidoglycan in the bacterial cell wall leading to rapid killing of Gram-positive organisms; however, this mechanism cannot account for the protective effect of lysozyme against Gram-negative bacteria following infection of transgenic mice. The current study was therefore designed to test the hypothesis that the catalytic activity (muramidase activity) of lysozyme is not required for bacterial killing in vivo. Substitution of serine for aspartic acid at position 53 (D53S) in mouse lysozyme M completely ablated muramidase activity. Muramidase-deficient recombinant lysozyme (LysMD53S) killed both Gram-positive and Gram-negative bacteria in vitro. Targeted expression of LysMD53S in the respiratory epithelium of wild type (LysM+/+/LysMD53S) or lysozyme M null mice (LysM-/-/LysMD53S) resulted in elevated lysozyme protein in the airspaces without any increase in muramidase activity. Intratracheal challenge of transgenic mice with Gram-positive or Gram-negative bacteria resulted in a significant increase in bacterial burden in LysM-/-mice that was completely reversed by targeted expression of LysMD53S. These results indicate that the muramidase activity of lysozyme is not essential for bacterial killing in vitro or in vivo.
|School:||University of Cincinnati|
|Department:||Molecular and Cellular Physiology|
|School Location:||United States -- Ohio|
|Source:||DAI-B 79/10(E), Dissertation Abstracts International|
|Keywords:||Anti-microbial activity, Cationic peptides, Innate immune system, Lysozyme, Muramidase, Pulmonary biology|
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