title: Rac1, RhoA, and Cdc42 participate in HeLa cell invasion by group B streptococcus.
abstract: The group B streptococcus (GBS) is an important human pathogen with the ability to cause invasive disease. To do so, the bacteria must invade host cells. It has been well documented that GBS are able to invade a variety of nonphagocytic host cell types, and this process is thought to involve a number of pathogen-host cell interactions. While some of the molecular aspects of the GBS-host cell invasion process have been characterized, many events still remain unclear. The objective of this investigation was to evaluate the role of the Rho-family GTPases Rac, Rho, and Cdc42 in GBS invasion into epithelial cells. The epithelial cell invasion process was modeled using HeLa 229 cell culture. Treatment of HeLa cells with 10 microM compactin, a pan-GTPase inhibitor, abolished GBS internalization, suggesting that GTPases are involved in the GBS invasion process. The addition of Toxin B or exoenzyme C3 to HeLa cells before GBS infection reduced invasion by 50%, further suggesting that the Rho-family GTPases are involved in GBS entry. Examining invasion of GBS into HeLa cells with altered genetic backgrounds was used to confirm these findings; GBS invasion into HeLa cells transiently transfected with dominant negative Rac1, Cdc42, or RhoA reduced invasion by 75%, 51%, and 42%, respectively. Results of this study suggest that the Rho-family GTPases are required for efficient invasion of HeLa cells by GBS.
authors.affiliation: The Department of Laboratory Medicine and Pathology, The University of Alberta, Edmonton, AB, Canada.
authors.forename: Carey-Ann D
authors.initials: CA
authors.lastname: Burnham
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Shokoples
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tyrrell
mesh_terms: D036002:ADP Ribose Transferases / Q000633:toxicity; D001426:Bacterial Proteins / Q000633:toxicity; D001427:Bacterial Toxins / Q000633:toxicity; D001905:Botulinum Toxins / Q000633:toxicity; D015169:Colony Count, Microbial / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000382:microbiology*; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors; D006367:HeLa Cells; D006801:Humans; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013292:Streptococcus agalactiae / Q000254:growth & development* / Q000502:physiology; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; C031815:toxB protein, Clostridium difficile; C012258:mevastatin; D008148:Lovastatin; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D020558:GTP Phosphohydrolases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein