title: Analysis of nontypeable haemophilus influenzae phase-variable genes during experimental human nasopharyngeal colonization.
abstract: BACKGROUND
  Studies of nontypeable Haemophilus influenzae (NTHi) have demonstrated that a number of genes associated with infectivity have long repeat regions associated with phase variation in expression of the respective gene. The purpose of this study was to determine the genes that underwent phase variation during a 6-day period of experimental human nasopharyngeal colonization.
  
  
  METHODS
  Strain NTHi 2019Str(R)1 was used to colonize the nasopharynx of human subjects in a study of experimental colonization. Thirteen phase-variable genes were analyzed in NTHi 2019Str(R)1. Samples of NTHi 2019Str(R)1 were cultured from subjects during the 6-day colonization period. We used capillary electrophoresis and Roche 454 pyrosequencing to determine the number of repeats in each gene from each sample.
  
  
  RESULTS
  A significant number of samples switched licA and igaB from phase off in the inoculated strain to phase on during the 4-day period of observation. lex2A also showed variability as compared to baseline, but the differences were not significant. The remaining genes showed no evidence of phase variation.
  
  
  CONCLUSIONS
  Our studies suggest that the phase-on genotypes of licA and igaB are important for early human nasopharynx colonization. lex2A showed a trend from phase off to phase on, suggesting a potentially important role in the colonization process.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Poole
authors.forename: Eric
authors.initials: E
authors.lastname: Foster
authors.forename: Kathryn
authors.initials: K
authors.lastname: Chaloner
authors.forename: Jason
authors.initials: J
authors.lastname: Hunt
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jennings
authors.forename: Thomas
authors.initials: T
authors.lastname: Bair
authors.forename: Kevin
authors.initials: K
authors.lastname: Knudtson
authors.forename: Erik
authors.initials: E
authors.lastname: Christensen
authors.forename: Robert S
authors.initials: RS
authors.lastname: Munson
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Winokur
authors.forename: Michael A
authors.initials: MA
authors.lastname: Apicella
mesh_terms: D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000235:genetics; D002353:Carrier State / Q000382:microbiology*; D019075:Electrophoresis, Capillary; D020869:Gene Expression Profiling; D006192:Haemophilus Infections / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000235:genetics*; D006801:Humans; D008962:Models, Theoretical; D009305:Nasopharynx / Q000382:microbiology*; D017422:Sequence Analysis, DNA
chemical_list: D000942:Antigens, Bacterial
keywords: Haemophilus influenzae; igaB; lex2A nasopharyngeal colonization; licA; phase variation