aeruginosa is capable of performing denitrification at relatively high dissolved oxygen levels [28–30]. The physiological role for aerobic denitrification has not yet been fully elucidated. From a purely energetic standpoint, the advantage of co-respiration using both oxygen and nitrate is not obvious, since energetically denitrification buy CBL0137 is less efficient than aerobic respiratory pathways. However, this apparent paradox has been addressed in different bacteria and additional physiological roles have been suggested for various denitrification enzymes [31]. Our own analysis of global gene expression in P. aeruginosa in this study points to role of aerobic denitrification as a response to media acidification

assuming that aerobic denitrification might be essential for P. aeruginosa to maintain an optimum pH during infection of the gut. Similarly, the role of arginine

deiminase system is far more complex than merely to support cellular survival under anaerobiosis. In fact, the major function of this system in a variety of lactic acid bacteria and Streptococcal species has been shown to protect organisms against acid damage [24, 32]. For P. aeruginosa this role has not been previously demonstrated and therefore is novel. Cilengitide chemical structure Finally we observed attenuated expression of multiple stress-related and resistance-related genes at pH 7.5. Taken Pevonedistat in vitro together these findings suggest that pH 7.5 is more physiologic for P. aeruginosa and that P. aeruginosa may regulate its environmental pH to facilitate its colonization and/or Nabilone invasion. Table 2 P. aeruginosa genes with decreased expression at pH 7.5 vs pH 6.0 PA ID Gene name Fold expression pH7.5 vs pH6.0 Function    Subsystem

PA5170 arcD -1.91 Arginine/ornithine antiporter ArcD    Arginine deiminase pathway PA5171 arcA -4.3 Arginine deiminase (EC 3.5.3.6)    Arginine deiminase pathway PA5172 arcB -2.82 Ornithine carbamoyltransferase (EC 2.1.3.3)    Arginine deiminase pathway PA5173 arcC -2.13 Carbamate kinase (EC 2.7.2.2)    Arginine deiminase pathway PA0530   -2.49 Acetylornithine aminotransferase (EC 2.6.1.11)    Arginine_Biosynthesis_extended PA3865   -2.74 Arginine/ornithine ABC transporter, periplasmic arginine/ornithine binding protein    Arginine deiminase pathway PA1540   -2.14 Spermidine export protein mdtI    Small_Multidrug_Resistance PA1541   -3.44 Spermidine export protein mdtJ    Small_Multidrug_Resistance PA0509 nirN -3.39 Nitrite reductase associated c-type cytochorome NirN    Dissimilatory_nitrite_reductase PA0510   -4.39 Uroporphyrinogen-III methyltransferase (EC 2.1.1.107)    Dissimilatory_nitrite_reductase PA0511 nirJ -5.67 Heme d1 biosynthesis protein NirJ    Dissimilatory_nitrite_reductase PA0512   -1.84 Heme d1 biosynthesis protein NirH    Dissimilatory_nitrite_reductase PA0513   -1.76 Heme d1 biosynthesis protein NirG    Dissimilatory_nitrite_reductase PA0514 nirL -2.32 Heme d1 biosynthesis protein NirL    Dissimilatory_nitrite_reductase PA0515   -7.