The observation that the ratio of this protein

in sputum-grown to media-grown H. influenzae (4.764) was among the highest detected in the present study is consistent with the observation that the protein is prominently expressed during infection and suggests that antioxidant activity is important for survival of H. influenzae in the airways. Stress response Five stress related proteins were present in greater abundance during growth in sputum.These include GroEL, GroES, heat shock protein encoded by dnaJ, universal stress protein E and DNA-binding ferritin-like protein.The latter protein contains a DPS (DNA protein under starved conditions) domain PI3K Inhibitor Library chemical structure which non specifically binds DNA, protecting it from cleavage by reactive

oxygen species. The abundance of these proteins suggests that H. influenzae expresses a stress response during growth in the human respiratory tract. Uptake of nutrients and cofactors In see more addition to the anti oxidant and stress response observed, several proteins that were present in greater abundance during growth in sputum function in uptake in nutrients and cofactors.Four such proteins function directly in uptake of divalent cations, including 3 iron uptake proteins (yfeA, hitA, hxuB) and one zinc uptake protein (znuA).The environment in the human host has exceedingly low concentrations of free iron; thus human pathogens have evolved mechanisms to scavenge ALK inhibitor iron during infection.These results indicate that H. influenzae grows in an iron stressed condition in the human respiratory tract.The presence of increased levels of several other proteins that function in transport of various nutrients and other molecules (proteins encoded by

(acpC, oppB, hslVU, uspE, pstB, tolQ, metQ, orfG) indicates that the human respiratory tract is relatively deficient in nutrients causing H. influenzae to upregulate certain transport systems. Gawronski et al [49] developed a novel approach of negative selection technology involving challenging SPTLC1 mice with a mutant library of H. influenzae and identifying genes that were required to delay clearance of bacteria from the lungs.Genes that were implicated in survival in mouse lung included those that play potential roles in survival in nutrient limitation, oxidative stress and exposure to antimicrobial perturbations.While substantial differences between individual genes identified as important in mouse lungs compared to the proteins that were present in increased abundance in human sputum in the present study, the overall classes of genes/proteins show strong parallels.In particular, the expression in both systems of genes/proteins that function in survival in oxidative stress and nutrient limitation are consistent with the concept that these conditions exist in the respiratory tract and H. influenzae must express molecules to survive in these conditions in order cause respiratory tract infection.