title: Quantitative proteomics (2-D DIGE) reveals molecular strategies employed by Burkholderia cenocepacia to adapt to the airways of cystic fibrosis patients under antimicrobial therapy.
abstract: Chronic respiratory infections caused by Burkholderia cenocepacia in patients with cystic fibrosis (CF) are characterized by low responsiveness to antibiotic therapy and, in general, to a more rapid decline of lung function. To get clues into the molecular mechanisms underlying the adaptive strategies employed to deal with the stressing conditions of the CF lung including antibiotic therapy, quantitative proteomics (2-D DIGE) was used to compare the expression programs of two clonal isolates retrieved from a chronically infected CF patient. Isolate IST439 was the first bacterium recovered while the clonal variant IST4113 was obtained after 3 years of persistent infection and intravenous therapy with ceftazidime/gentamicin. This isolate exhibits higher resistance levels towards different classes of antimicrobials. Proteins of the functional categories Energy metabolism, Translation, Nucleotide synthesis, Protein folding and stabilization are more abundant in IST4113, compared with IST439, suggesting an increased protein synthesis, DNA repair and stress resistance in IST4113. The level of proteins involved in peptidoglycan, membrane lipids and lipopolysaccharide synthesis is also altered and proteins involved in iron binding and transport are more abundant in IST4113. The quantitative comparison of the two proteomes suggests a genetic adaptation leading to increased antimicrobial resistance and bacterial persistence in the CF airways.
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Department of Bioengineering, Instituto Superior Técnico, Technical University of Lisbon, Lisbon, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Madeira
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Santos
authors.forename: Carla P
authors.initials: CP
authors.lastname: Coutinho
authors.forename: Ana
authors.initials: A
authors.lastname: Pinto-de-Oliveira
authors.forename: Isabel
authors.initials: I
authors.lastname: Sá-Correia
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019121:Burkholderia Infections / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D057508:Burkholderia cenocepacia / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D002442:Ceftazidime / Q000008:administration & dosage / Q000627:therapeutic use; D018929:Cell Culture Techniques; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression / Q000187:drug effects; D005839:Gentamicins / Q000008:administration & dosage / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D040901:Proteomics; D012137:Respiratory System / Q000382:microbiology / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005839:Gentamicins; D006360:Heat-Shock Proteins; D033862:Iron-Binding Proteins; D002442:Ceftazidime; D045643:DNA Repair Enzymes