The course of Lazertinib purchase COPD, the fourth leading cause of death in the world, is characterized by intermittent worsening called exacerbations. Approximately half of exacerbations are caused by bacterial infection, with H. influenzae being the most frequent bacterial cause [2]. In addition to causing exacerbations, H. influenzae also chronically colonizes the lower airways of adults with COPD. The normal human respiratory tract is sterile below the vocal cords, as determined by culture. However, in adults with COPD, the lower airways are colonized by bacteria,

with H. influenzae as the most common pathogen in this setting [4–7]. The human respiratory tract is a hostile environment for bacteria. Nutrients and energy sources are limited. In the setting of COPD, airways are characterized by an oxidant/antioxidant imbalance and by an inflammatory milieu [8–12]. Thus to survive and cause infection in the human respiratory tract, H. influenzae must express proteins and other molecules to enable persistence in this unique environment. In previous work, we characterized the proteome of H. influenzae that was grown in pooled human sputum obtained from adults with COPD in an effort to simulate the environment of the human airways in COPD [13]. In comparison to the same strain of H. influenzae grown in chemically defined media, 31 proteins were present in greater abundance

in sputum grown-conditions at a ratio of > 1.5 compared to media-grown conditions. These included MK-8776 research buy antioxidant proteins, stress response proteins, proteins that function in the uptake of divalent cations and proteins that function in the uptake of various molecules. Interestingly, the second most abundant protein Avelestat (AZD9668) with regard to the ratio of sputum-grown to media-grown analysis was urease C, the alpha subunit of urease, which was present in an abundance of 7-fold greater in sputum-grown conditions compared to media-grown conditions. This is an interesting finding in light of the observation by Mason et al [14] who monitored gene expression by H. influenzae in the middle ear of

a chinchilla, the most widely used animal model of otitis media. The gene that encodes urease accessory protein, ureH, was induced 3.9-fold in bacterial cells in the middle ear compared to baseline. These two genes, ureC and ureH are part of the urease gene cluster and were among the most highly up regulated genes. These observations suggest that expression of urease is important for survival and growth of H. influenzae in the respiratory tract. Ureases are nickel dependent enzymes that catalyze the hydrolysis of urea to form ammonia and carbon dioxide [15, 16]. Urease is best studied as a virulence factor in Helicobacter pylori which colonizes the stomach and Proteus mirabilis which causes urinary tract infections [17–23]. Urease is also important for survival and pathogenesis of several bacterial species [24–27].