title: Marker genes for the metabolic adaptation of Pseudomonas aeruginosa to the hypoxic cystic fibrosis lung environment.
abstract: Pseudomonas aeruginosa is the leading pathogen of chronic cystic fibrosis (CF) lung infection. Life-long persistence in the inflamed and ever fluctuating CF lungs results in the selection of a variety of changes in P. aeruginosa physiology. Accumulating evidence suggests that especially metabolic changes support the survival and growth of P. aeruginosa within the hypoxic and nutritious CF mucus. To investigate if metabolic adaptations we described for hypermutable P. aeruginosa from late CF lung disease (Hoboth et al., 2009. J. Infect. Dis., pp. 118-130) may represent specific changes in response to the selective conditions within the oxygen-restricted CF mucus, we determined the expression of a set of genes during aerobic and hypoxic growth in LB and the artificial sputum medium ASM. We further focused on the regulation of the two isocitrate dehydrogenases Icd and Idh. Interestingly, both isoenzymes may replace each other under aerobic and hypoxic conditions. The NADPH- and RpoS-dependent Icd seems to be the leading isoenzyme under prolonged oxygen limitation and stationary growth phase. LacZ reporter analysis revealed that oxygen-restriction increased the expression levels of azu, cbb3-1, cbb3-2, ccpR, icd, idh and oprF gene, whereas himD and nuoA are increasingly expressed only during hypoxic growth in ASM. Overexpression of the anaerobic regulator Anr improved the expression of azu, ccpR, cbb3-2 and icd. In summary, expression of azu, cbb3-1, cbb3-2, ccpR, icd, idh, oprF, himD, and nuoA appeared to be beneficial for the growth of P. aeruginosa under hypoxic conditions indicating these genes may represent marker genes for the metabolic adaptation to the CF lung environment.
authors.affiliation: Department of Dermatology, Regensburg University Hospital, Germany; Max von Pettenkofer Institute for Hygiene und Medical Microbiology, Ludwig-Maximilians-University, Munich.
authors.forename: Anja
authors.initials: A
authors.lastname: Eichner
authors.affiliation: Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Günther
authors.affiliation: Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Arnold
authors.affiliation: Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Schobert
authors.affiliation: Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Heesemann
authors.affiliation: Johann Wolfgang Goethe-University, Frankfurt/Main, Germany. Electronic address: michael.hogardt@kgu.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Hogardt
mesh_terms: D000220:Adaptation, Biological; D003550:Cystic Fibrosis / Q000150:complications* / Q000473:pathology; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000382:microbiology
chemical_list: D005819:Genetic Markers; D007521:Isocitrate Dehydrogenase
keywords: Artificial sputum medium; Cystic fibrosis; Isocitrate dehydrogenase; Metabolic adaptation; Oxygen-limitation; Pseudomonas aeruginosa