Thus, we speculate that the urease of H. influenzae facilitates nitrogen assimilation in the nutritionally limited environment of the human airways and the middle ear space. Two indirect lines of evidence have suggested that H. influenzae

expresses urease during human infection. Mason et al [14] showed that urease H is expressed during infection of the middle ear in chinchillas and Qu et al [13] showed that urease C was expressed in markedly increased abundance during growth in pooled human sputum. The present study advances those observations by showing directly that H. influenzae expresses urease during airway infection in adults who experienced exacerbations of COPD. Paired pre and post infection serum samples were subjected to ELISA with purified recombinant urease C to characterize the antibody response to urease following infection. Because check details the pre infection serum samples were collected one month prior to acquisition of the infecting strain of H. influenzae, an increase in the level of antibody to urease indicates the development of new antibodies following infection.

All serum samples had detectable levels of antibody to urease and 7 of 18 patients developed significantly increased levels following infection compared to their own pre infection levels (Figure MCC950 molecular weight 9). This frequency of antibody response following bacterial infection is typical as heterogeneity in immune responses to bacterial antigens among individuals is a hallmark of COPD [47, 48]. Note also that recombinant purified urease C was used in the ELISA and this protein is only one of 3 proteins that comprise the urease complex; thus, a urease C-based ELISA may underestimate the frequency of new antibody responses to urease following

infection. These results indicate Tyrosine-protein kinase BLK that H. influenzae expresses urease during exacerbations of COPD and that urease is a target of human antibody responses. An important result from the present study is the observation that urease functions to mediate survival of H. influenzae in an acid environment. Urease mediates survival in low pH as a virulence MLN2238 purchase mechanism in other bacteria, notably H. pylori which must survive in the stomach. Other selected respiratory pathogens express urease but the role of urease in pathogenesis of respiratory tract infection is unclear [49, 50]. Microenvironments in the human respiratory tract are likely low pH, consistent with the speculation that the high level of expression of urease in the respiratory tract mediates survival in acid microenvironments. Furthermore, H. influenzae is now known to invade and persist in respiratory epithelial cells and macrophages, suggesting that withstanding lower pH in intracellular compartments may be a virulence mechanism [51–53]. Conclusions The present study demonstrates that 1) The ureA-ureH gene cluster of H.