title: Identification of components of the host type IA phosphoinositide 3-kinase pathway that promote internalization of Listeria monocytogenes.
abstract: The bacterial pathogen Listeria monocytogenes causes food-borne illnesses resulting in gastroenteritis, meningitis, or abortion. Listeria promotes its internalization into some human cells through binding of the bacterial surface protein InlB to the host receptor tyrosine kinase Met. The interaction of InlB with the Met receptor stimulates host signaling pathways that promote cell surface changes driving bacterial uptake. One human signaling protein that plays a critical role in Listeria entry is type IA phosphoinositide 3-kinase (PI 3-kinase). The molecular mechanism by which PI 3-kinase promotes bacterial internalization is not understood. Here we perform an RNA interference (RNAi)-based screen to identify components of the type IA PI 3-kinase pathway that control the entry of Listeria into the human cell line HeLa. The 64 genes targeted encode known upstream regulators or downstream effectors of type IA PI 3-kinase. The results of this screen indicate that at least 9 members of the PI 3-kinase pathway play important roles in Listeria uptake. These 9 human proteins include a Rab5 GTPase, several regulators of Arf or Rac1 GTPases, and the serine/threonine kinases phosphoinositide-dependent kinase 1 (PDK1), mammalian target of rapamycin (mTor), and protein kinase C-ζ. These findings represent a key first step toward understanding the mechanism by which type IA PI 3-kinase controls bacterial internalization.
authors.affiliation: Department of Molecular Biology and Microbiology, College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida, USA.
authors.forename: Shahanawaz
authors.initials: S
authors.lastname: Jiwani
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Georgina C
authors.initials: GC
authors.lastname: Dowd
authors.forename: Antonella
authors.initials: A
authors.lastname: Gianfelice
authors.forename: Phannipha
authors.initials: P
authors.lastname: Pichestapong
authors.forename: Balramakrishna
authors.initials: B
authors.lastname: Gavicherla
authors.forename: Neyda
authors.initials: N
authors.lastname: Vanbennekom
authors.forename: Keith
authors.initials: K
authors.lastname: Ireton
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology*; D020868:Gene Silencing; D005820:Genetic Testing; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; C095768:inlB protein, Listeria monocytogenes; D058543:Class Ia Phosphatidylinositol 3-Kinase; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met