Intestinal P glycoprotein acts as a natural defense mechanism against Listeria monocytogenes.
Mechanisms by which the intestinal epithelium resists invasion by food-borne pathogens such as Listeria monocytogenes are an evolving area of research. Intestinal P glycoprotein is well known to limit the absorption of xenobiotics and is believed to act as a cytotoxic defense mechanism. The aim of this study was to determine if intestinal P glycoprotein is involved in host defense against L. monocytogenes. Caco-2 cells and a P-glycoprotein-overexpressing subclone (Caco-2/MDR) were employed in addition to mdr1a(-/-) mice and wild-type controls. In vitro invasion assays and in vivo experiments were employed to measure bacterial invasion and dissemination. In addition, L. monocytogenes proteins were labeled with [(35)S]methionine, and the transepithelial transport across Caco-2 monolayers was characterized in both directions. Overexpression of P glycoprotein in Caco-2/MDR cells led to increased resistance to L. monocytogenes invasion, whereas P-glycoprotein inhibition led to increased invasion. Flux of [(35)S]methionine-labeled L. monocytogenes proteins was significantly greater in the basolateral-to-apical direction than in the apical-to-basolateral direction, indicating dependence on an apically located efflux transporter. Moreover, inhibiting P glycoprotein reduced the basolateral-to-apical flux of the proteins. Early dissemination of L. monocytogenes from the gastrointestinal tract was significantly greater in the mdr1a(-/-) mice than in wild-type controls. Expression and function of intestinal P glycoprotein is an important determinant in resistance to early invasion of L. monocytogenes.
Neudeck
Brien L
BL
University of Wisconsin School of Pharmacy, 777 Highland Avenue, Madison, WI 53705-2222, USA. blneudeck@pharmacy.wisc.edu
Loeb
Jennifer M
JM
Faith
Nancy G
NG
Czuprynski
Charles J
CJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D018938:Caco-2 Cells; D004077:Digoxin / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D013462:Sulfur Radioisotopes / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001426:Bacterial Proteins; D013462:Sulfur Radioisotopes; D004077:Digoxin