Pathogenic mechanisms induced by microbial proteases in microbial infections.
Most bacterial and fungal proteases excreted into infected hosts exhibit a wide range of pathogenic potentials ranging from pain, edema or even shock to translocation of bacteria from the site of infection into systemic circulation, thus resulting in septicemia. The basic mechanism or principle common to all these phenomena is explained by kinin generation, either directly from high- and/or low-molecular weight kininogens or indirectly via activation of the bradykinin generating cascade: i.e. Hageman factor-->activated Hageman factor-->prekallikrein-->kallikrein-->high-molecular weight kininogen-->bradykinin. Some bacterial proteases are also involved in activation of other host protease zymogens such as plasminogen, procollagenase (matrix metallo proteases) and proenzymes of the clotting system. Furthermore, most bacterial proteases are not only resistant to plasma protease inhibitors of the hosts, most of which belong to a group of serine protease inhibitors called serpins (serine protease inhibitors), but they also quickly inactivate serpins. Some bacterial proteases may also activate bacterial toxins thus rendering toxigenic pathogenesis. They are also capable of degrading immunoglobulins and components of the complement system and facilitate propagation of micro organisms. All in all, microbial proteases are very critical in enhancing pathogenesis of severe diseases. It is also noteworthy that bacterial cell wall components themselves, i.e. endotoxin (or lipopolysaccharide) of gram negative bacteria and teichoic/lipoteichoic acid of gram positive bacteria, are also able to activate the bradykinin generating cascade-involving activation of Hageman factor as mentioned above.
Maeda
H
H
Department of Microbiology, Kumamoto University School of Medicine, Japan.
Yamamoto
T
T
D000818:Animals; D001419:Bacteria / Q000201:enzymology / Q000472:pathogenicity*; D001424:Bacterial Infections / Q000382:microbiology*; D001777:Blood Coagulation; D001920:Bradykinin / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology; D010450:Endopeptidases / Q000378:metabolism*; D005658:Fungi / Q000201:enzymology / Q000472:pathogenicity*; D006801:Humans; D009181:Mycoses / Q000382:microbiology*; D009369:Neoplasms / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism
D011480:Protease Inhibitors; D003165:Complement System Proteins; D010450:Endopeptidases; D001920:Bradykinin