Engulfment of Neisseria gonorrhoeae: Revealing Distinct Processes of Bacterial Entry by Individual Carcinoembryonic Antigen-Related Cellular Adhesion Molecule Family Receptors
AUTOR(ES)
McCaw, Shannon E.
FONTE
American Society for Microbiology
RESUMO
Individual Neisseria gonorrhoeae colony opacity-associated (Opa) protein variants can bind up to four different carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) receptors. Most human cells encountered by gonococci express a combination of CEACAM receptors, thereby complicating the elucidation of intracellular signaling pathways triggered by individual receptors. Here, we compare the process of bacterial engulfment by a panel of stably transfected HeLa epithelial cell lines expressing each CEACAM receptor in isolation. CEACAM1 and CEACAM3 each contain proteinaceous transmembrane and cytoplasmic domains; however, the processes of neisserial uptake mediated by these receptors differ with respect to their susceptibilities to both tyrosine kinase inhibitors and the actin microfilament-disrupting agent cytochalasin D. Neisserial uptake mediated by glycosylphosphatidylinositol (GPI)-anchored CEACAM5 and CEACAM6 was not significantly affected by any of a broad spectrum of inhibitors tested. However, cleavage of the GPI anchor by phosphatidylinositol-specific phospholipase C reduced bacterial uptake by HeLa cells expressing CEACAM5, consistent with a single zipper-like mechanism of uptake mediated by this receptor. Regardless of the CEACAM receptor expressed, internalized gonococci were effectively killed by a microtubule-dependent process that required acidification of the bacterium-containing phagosome. Given the phase-variable nature of neisserial Opa proteins, these results indicate that the mechanism of bacterial engulfment and the cellular response to gonococcal infection depend on both the receptor specificities of the neisserial Opa protein variants expressed and the spectrum of CEACAM receptors present on target cells, each of which determines the combination of receptors ultimately engaged.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=387857Documentos Relacionados
- Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Modulates Experimental Autoimmune Encephalomyelitis via an iNKT Cell-Dependent Mechanism
- Carcinoembryonic Antigen-Related Cell Adhesion Molecule 10 Expressed Specifically Early in Pregnancy in the Decidua Is Dispensable for Normal Murine Development
- Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59.
- Molecular cloning and expression of cDNA for a carcinoembryonic antigen-related fetal liver glycoprotein.
- Bgp2, a new member of the carcinoembryonic antigen-related gene family, encodes an alternative receptor for mouse hepatitis viruses.