title: Expression of IgA Proteases by Haemophilus influenzae in the Respiratory Tract of Adults With Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  Immunoglobulin (Ig)A proteases of Haemophilus influenzae are highly specific endopeptidases that cleave the hinge region of human IgA1 and also mediate invasion and trafficking in human respiratory epithelial cells, facilitating persistence of H. influenzae. Little is known about the expression of IgA proteases in clinical settings of H. influenzae infection.
  
  
  METHODS
  We identified and characterized IgA protease genes in H. influenzae and studied their expression and proteolytic specificity, in vitro and in vivo in 169 independent strains of H. influenzae collected longitudinally over 10 years from adults with chronic obstructive pulmonary disease.
  
  
  RESULTS
  The H. influenzae pangenome has 2 alleles of IgA protease genes; all strains have igaA, and 40% of strains have igaB. Each allele has 2 variants with differing proteolytic specificities for human IgA1. A total of 88% of 169 strains express IgA protease activity. Expression of the 4 forms of IgA protease varies among strains. Based on the presence of IgA1 fragments in sputum samples, each of the different forms of IgA protease is selectively expressed in the human airways during infection.
  
  
  CONCLUSIONS
  Four variants of IgA proteases are variably expressed by H. influenzae during infection of the human airways.
authors.affiliation: Division of Infectious Diseases Department of Microbiology and Immunology Clinical and Translational Research Center, University at Buffalo, State University of New York.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Murphy
authors.affiliation: Division of Infectious Diseases Clinical and Translational Research Center, University at Buffalo, State University of New York.
authors.forename: Charmaine
authors.initials: C
authors.lastname: Kirkham
authors.affiliation: Department of Microbiology and Immunology Clinical and Translational Research Center, University at Buffalo, State University of New York.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Jones
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine Veterans Affairs Western New York Healthcare System, Buffalo, New York.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Department of Molecular Biophysics and Biochemistry, W.M. Keck Biotechnology Resource Laboratory.
authors.forename: Yong
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut.
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Pettigrew
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D006192:Haemophilus Infections / Q000150:complications / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000382:microbiology*; D012141:Respiratory Tract Infections / Q000150:complications / Q000382:microbiology; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013183:Sputum / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase
keywords: Haemophilus influenzae; IgA protease; airway infection; chronic obstructive pulmonary disease; endopeptidase; exacerbation of COPD; respiratory tract colonization; respiratory tract infection