Abstract
BackgroundNontypeable Haemophilus influenzae is a common cause of otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Prior studies have shown that H. influenzae expresses abundant urease during growth in the middle ear of the chinchilla and in pooled human sputum, suggesting that expression of urease is important for colonization and infection in the hostile environments of the middle ear and in the airways in adults. Virtually nothing else is known about the urease of H. influenzae, which was characterized in the present study.ResultsAnalysis by reverse transcriptase PCR revealed that the ure gene cluster is expressed as a single transcript. Knockout mutants of a urease structural gene (ureC) and of the entire ure operon demonstrated no detectable urease activity indicating that this operon is the only one encoding an active urease. The ure operon is present in all strains tested, including clinical isolates from otitis media and COPD. Urease activity decreased as nitrogen availability increased. To test the hypothesis that urease is expressed during human infection, purified recombinant urease C was used in ELISA with pre acquisition and post infection serum from adults with COPD who experienced infections caused by H. influenzae. A total of 28% of patients developed new antibodies following infection indicating that H. influenzae expresses urease during airway infection. Bacterial viability assays performed at varying pH indicate that urease mediates survival of H. influenzae in an acid environment.ConclusionsThe H. influenzae genome contains a single urease operon that mediates urease expression and that is present in all clinical isolates tested. Nitrogen availability is a determinant of urease expression. H. influenzae expresses urease during human respiratory tract infection and urease is a target of the human antibody response. Expression of urease enhances viability in an acid environment. Taken together, these observations suggest that urease is important for survival and replication of H. influenzae in the human respiratory tract.
Highlights
Nontypeable Haemophilus influenzae is a common cause of otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD)
Identification of urease gene cluster The a subunit of urease, which was present in increased abundance in H. influenzae grown in pooled human sputum based on proteomic analysis, is a protein of 572 amino acids with a predicted molecular mass of 62 kilodaltons that is encoded by urease structural gene (ureC) [13]
The present study demonstrates that 1) The ureA-ureH gene cluster of H. influenzae is exclusively responsible for urease production because knock out mutants show no urease activity
Summary
Nontypeable Haemophilus influenzae is a common cause of otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). H. influenzae is a common and important human pathogen, causing otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD) [1,2,3]. In addition to causing exacerbations, H. influenzae chronically colonizes the lower airways of adults with COPD. In adults with COPD, the lower airways are colonized by bacteria, with H. influenzae as the most common pathogen in this setting [4,5,6,7]
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