title: The HMW1 and HMW2 Adhesins Enhance the Ability of Nontypeable Haemophilus influenzae To Colonize the Upper Respiratory Tract of Rhesus Macaques.
abstract: Nontypeable Haemophilus influenzae (NTHi) initiates infection by colonizing the upper respiratory tract and is a common cause of localized respiratory tract disease. Previous work has established that the NTHi HMW1 and HMW2 proteins are potent adhesins that mediate efficient in vitro adherence to cultured human respiratory epithelial cells. In this study, we used a rhesus macaque model to assess the contributions of HMW1 and HMW2 to in vivo colonization. In experiments involving inoculation of individual isogenic derivatives of NTHi strain 12, the parent strain expressing both HMW1 and HMW2 and the mutant strains expressing either HMW1 or HMW2 were able to colonize more frequently than the double mutant strain lacking HMW1 and HMW2. In competition experiments, the parent strain efficiently outcompeted the double mutant lacking HMW1 and HMW2. Colonization with strains expressing HMW2 resulted in development of antibody against HMW2 in a number of the animals, demonstrating that colonization can stimulate an antibody response. In conclusion, we have established that the HMW1 and HMW2 adhesins play a major role in facilitating colonization of the upper respiratory tract of rhesus macaques, in some cases associated with stimulation of an immune response.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Rempe
authors.affiliation: The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Porsch
authors.affiliation: The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Jolaine M
authors.initials: JM
authors.lastname: Wilson
authors.affiliation: The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA stgemeiiij@email.chop.edu.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: St Geme
mesh_terms: D018829:Adhesins, Bacterial / Q000502:physiology*; D000818:Animals; D000907:Antibodies, Bacterial; D001422:Bacterial Adhesion / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D004195:Disease Models, Animal; D006192:Haemophilus Infections / Q000276:immunology / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000276:immunology / Q000472:pathogenicity*; D008253:Macaca mulatta; D010614:Pharynx / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology*; D014132:Trachea / Q000382:microbiology
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; C117431:HMW1 protein, bacteria; C117432:HMW2 protein, bacteria