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Infection and Immunity, September 2003, p. 5149-5155, Vol. 71, No. 9
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.9.5149-5155.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Division of Pediatric Infectious Diseases, University of TexasHouston Medical School, Houston, Texas,1 Max von Pettenkofer-Institut Bakteriologie, Munich,2 Vaccine Research Group, German Research Centre for Biotechnology, Braunschweig, Germany3
Received 13 December 2002/ Returned for modification 11 March 2003/ Accepted 6 May 2003
Enteropathogenic Escherichia coli (EPEC) is an important cause of infant diarrhea in developing countries. EPEC uses a type III secretory system to deliver effector proteins into the host cell. These proteins cause the characteristic attaching and effacing lesion on enterocytes. Lactoferrin, a glycoprotein present in human milk, inhibits EPEC adherence to mammalian cells. To determine the effect of lactoferrin on the initial host cell attachment step that is mediated by the type III secretory system, we focused on EPEC-induced actin polymerization in HEp2 cells, on the hemolytic activity, and on measurement of E. coli secreted proteins A, B, and D (EspABD). Lactoferrin blocked EPEC-mediated actin polymerization in HEp2 cells and blocked EPEC-induced hemolysis. The mechanism of this inhibition was lactoferrin-mediated degradation of secreted proteins necessary for bacterial contact and pore formation, particularly EspB. The proteolytic effect of lactoferrin was prevented by serine protease inhibitors. This disruption of the type III secretory system implies that lactoferrin could provide broad cross protection against the enteropathogens that share this mechanism.
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