title: Quantitative proteomic analysis of host--pathogen interactions: a study of Acinetobacter baumannii responses to host airways.
abstract: BACKGROUND
  Acinetobacter baumannii is a major health problem. The most common infection caused by A. baumannii is hospital acquired pneumonia, and the associated mortality rate is approximately 50%. Neither in vivo nor ex vivo expression profiling has been performed at the proteomic or transcriptomic level for pneumonia caused by A. baumannii. In this study, we characterized the proteome of A. baumannii under conditions that simulate those found in the airways, to gain some insight into how A. baumannii adapts to the host and to improve knowledge about the pathogenesis and virulence of this bacterium. A clinical strain of A. baumannii was grown under different conditions: in the presence of bronchoalveolar lavage fluid from infected rats, of RAW 264.7 cells to simulate conditions in the respiratory tract and in control conditions. We used iTRAQ labelling and LC-MALDI-TOF/TOF to investigate how A. baumannii responds on exposure to macrophages/BALF.
  
  
  RESULTS
  179 proteins showed differential expression. In both models, proteins involved in the following processes were over-expressed: (i) pathogenesis and virulence (OmpA, YjjK); (ii) cell wall/membrane/envelope biogenesis (MurC); (iii) energy production and conversion (acetyl-CoA hydrolase); and (iv) translation (50S ribosomal protein L9). Proteins involved in the following were under-expressed: (i) lipid metabolism (short-chain dehydrogenase); (ii) amino acid metabolism and transport (aspartate aminotransferase); (iii) unknown function (DNA-binding protein); and (iv) inorganic ion transport and metabolism (hydroperoxidase).
  
  
  CONCLUSIONS
  We observed alterations in cell wall synthesis and identified 2 upregulated virulence-associated proteins with >15 peptides/protein in both ex vivo models (OmpA and YjjK), suggesting that these proteins are fundamental for pathogenesis and virulence in the airways. This study is the first comprehensive overview of the ex vivo proteome of A. baumannii and is an important step towards identification of diagnostic biomarkers, novel drug targets and potential vaccine candidates in the fight against pneumonia caused by A. baumannii.
authors.affiliation: Microbiology Division, INIBIC-Complejo Hospitalario Universitario de la Coruña, A Coruña, Spain. jose.antonio.mendez.arredondo@sergas.es.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Méndez
authors.affiliation: Grupo de Proteomica-PBR2-ProteoRed/ISCIII-Servicio de Reumatologia, A Coruña, Spain. Jesus.Mateos.Martin@sergas.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Mateos
authors.affiliation: Microbiology Division, INIBIC-Complejo Hospitalario Universitario de la Coruña, A Coruña, Spain. Alejandro.Beceiro.Casas@sergas.es.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Beceiro
authors.affiliation: Microbiology Division, INIBIC-Complejo Hospitalario Universitario de la Coruña, A Coruña, Spain. malopedi@gmail.com.
authors.forename: María
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Microbiology Division, INIBIC-Complejo Hospitalario Universitario de la Coruña, A Coruña, Spain. MA.del.Mar.Tomas.Carmona@sergas.es.
authors.forename: María
authors.initials: M
authors.lastname: Tomás
authors.affiliation: Microbiology Division, INIBIC-Complejo Hospitalario Universitario de la Coruña, A Coruña, Spain. Margarita.Poza.Dominguez@sergas.es.
authors.forename: Margarita
authors.initials: M
authors.lastname: Poza
authors.affiliation: Microbiology Division, INIBIC-Complejo Hospitalario Universitario de la Coruña, A Coruña, Spain. German.Bou.Arevalo@sergas.es.
authors.forename: Germán
authors.initials: G
authors.lastname: Bou
mesh_terms: D040981:Acinetobacter baumannii / Q000502:physiology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000382:microbiology; D002460:Cell Line; D002473:Cell Wall / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D054884:Host-Pathogen Interactions / Q000235:genetics*; D050356:Lipid Metabolism; D008168:Lung / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008954:Models, Biological; D011014:Pneumonia / Q000473:pathology / Q000662:veterinary; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D020543:Proteome; D037521:Virulence Factors; D001219:Aspartate Aminotransferases