L12 enhances gonococcal transcytosis of polarized Hec1B cells via the lutropin receptor.
We previously reported that gonococci convert to a more invasive phenotype (Inv(+)GC) following contact with cells expressing the lutropin receptor (LHr) and that Inv(+)GC express a novel adhesin that interacts with LHr. We propose that this adhesion allows Inv(+)GC to activate LHr and induce gonococcal transcytosis, usurping normal LHr function in fallopian and endometrial epithelium, which is to transport fetal chorionic gonadotropin (hCG) into the mother. Infected polarized Hec1B monolayers, grown on collagen-coated transwells, showed that the passage of GC across the monolayer occurred rapidly, within 30 min, and proceeded at a constant rate with Inv(+)GC passage three-fold faster than GC grown in tissue culture media alone (Inv(-)GC). Electron microscopy found that Inv(+)GC triggered pseudopod formation around the bacterium, with GC found throughout the Hec1B targets within 30 min, while Inv(-)GC did neither. Pre-treatment of Inv(-)GC with recombinant ribosomal protein L12, a gonococcal "hCG-like" protein previously shown to increase invasion, also increased Inv(-)GC transcytosis to the rate of Inv(+)GC. This enhancement was completely abolished by addition of luteinizing hormone, a cognate ligand of LHr. This is convincing evidence that surface expressed L12 mediates gonococcal invasion and transcytosis via LHr, a mechanism that could be important in the development of invasive gonococcal disease in women.
Spence
Janice M
JM
Department of Microbiology and Immunology, School of Medicine and Dentistry, Rochester, NY 14642, U.S.A.
Tyler
Ryan E
RE
Domaoal
Robert A
RA
Clark
Virginia L
VL
D001426:Bacterial Proteins / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D002460:Cell Line; D016764:Cell Polarity; D002712:Chlorides; D004717:Endometrium / Q000166:cytology; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism / Q000494:pharmacology; D009344:Neisseria gonorrhoeae / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D011974:Receptors, LH / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D012269:Ribosomal Proteins / Q000378:metabolism* / Q000494:pharmacology
D001426:Bacterial Proteins; D002712:Chlorides; D005290:Ferric Compounds; D011974:Receptors, LH; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; C016700:ribosomal protein L7-L12; D007986:Luteinizing Hormone; C024555:ferric chloride