Human lactoferrin impairs virulence of Shigella flexneri.
Lactoferrin is a glycoprotein present in most human mucosal secretions, including human milk. Lactoferrin is bacteriostatic in low iron media and, in some settings, bactericidal. Lactoferrin impairs ability of Shigella flexneri serotype 5 strain M90T to invade HeLa cells. To determine the mechanism by which lactoferrin decreases invasiveness of Shigella organisms, its effect on the major virulence proteins responsible for bacterial uptake by host cells was evaluated. Lactoferrin induced degradation of invasion plasmid antigens IpaB and, to a lesser extent, IpaC, the key proteins responsible for bacteria-directed phagocytosis by mammalian cells. The lipid A-binding N-terminal portion of lactoferrin (residues 1-33) induces release of invasion antigens but does not induce degradation of IpaBC. Lactoferrin does not directly degrade previously released invasion plasmid antigens but works by making IpaBC susceptible to breakdown by surface-expressed protease(s).
Gomez
Henry F
HF
Division of Infectious Diseases, Department of Pediatrics, University of Texas-Houston Medical School, 77030, USA.
Ochoa
Theresa J
TJ
Carlin
Lily G
LG
Cleary
Thomas G
TG
D000942:Antigens, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion / Q000187:drug effects; D001426:Bacterial Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D008050:Lipid A / Q000378:metabolism; D010957:Plasmids; D011480:Protease Inhibitors / Q000494:pharmacology; D012763:Shigella flexneri / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D014774:Virulence
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008050:Lipid A; D011480:Protease Inhibitors; C087447:ipaB protein, Shigella; C092342:IpaC protein, Shigella; D007781:Lactoferrin