Lactoferrin impairs type III secretory system function in enteropathogenic Escherichia coli.
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.
Ochoa
Theresa J
TJ
Division of Pediatric Infectious Diseases, University of Texas-Houston Medical School, Houston, Texas 77040, USA.
Noguera-Obenza
Marita
M
Ebel
Frank
F
Guzman
Carlos A
CA
Gomez
Henry F
HF
Cleary
Thomas G
TG
D000199:Actins / Q000378:metabolism; D001422:Bacterial Adhesion / Q000187:drug effects; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D001426:Bacterial Proteins / Q000502:physiology; D002460:Cell Line; D003967:Diarrhea / Q000517:prevention & control; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology; D004927:Escherichia coli Infections / Q000517:prevention & control; D029968:Escherichia coli Proteins / Q000502:physiology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007781:Lactoferrin / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
D000199:Actins; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C087863:EaeB protein, E coli; D029968:Escherichia coli Proteins; C102051:EspA protein, E coli; C474481:EspD protein, E coli; D011994:Recombinant Proteins; D007781:Lactoferrin