title: Localization of Burkholderia cepacia complex bacteria in cystic fibrosis lungs and interactions with Pseudomonas aeruginosa in hypoxic mucus.
abstract: The localization of Burkholderia cepacia complex (Bcc) bacteria in cystic fibrosis (CF) lungs, alone or during coinfection with Pseudomonas aeruginosa, is poorly understood. We performed immunohistochemistry for Bcc and P. aeruginosa bacteria on 21 coinfected or singly infected CF lungs obtained at transplantation or autopsy. Parallel in vitro experiments examined the growth of two Bcc species, Burkholderia cenocepacia and Burkholderia multivorans, in environments similar to those occupied by P. aeruginosa in the CF lung. Bcc bacteria were predominantly identified in the CF lung as single cells or small clusters within phagocytes and mucus but not as "biofilm-like structures." In contrast, P. aeruginosa was identified in biofilm-like masses, but densities appeared to be reduced during coinfection with Bcc bacteria. Based on chemical analyses of CF and non-CF respiratory secretions, a test medium was defined to study Bcc growth and interactions with P. aeruginosa in an environment mimicking the CF lung. When test medium was supplemented with alternative electron acceptors under anaerobic conditions, B. cenocepacia and B. multivorans used fermentation rather than anaerobic respiration to gain energy, consistent with the identification of fermentation products by high-performance liquid chromatography (HPLC). Both Bcc species also expressed mucinases that produced carbon sources from mucins for growth. In the presence of P. aeruginosa in vitro, both Bcc species grew anaerobically but not aerobically. We propose that Bcc bacteria (i) invade a P. aeruginosa-infected CF lung when the airway lumen is anaerobic, (ii) inhibit P. aeruginosa biofilm-like growth, and (iii) expand the host bacterial niche from mucus to also include macrophages.
authors.affiliation: Cystic Fibrosis/Pulmonary Research and Treatment and Research Center, University of North Carolina, Chapel Hill, North Carolina, USA ues3@cornell.edu.
authors.forename: Ute
authors.initials: U
authors.lastname: Schwab
authors.affiliation: Cystic Fibrosis/Pulmonary Research and Treatment and Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Lubna H
authors.initials: LH
authors.lastname: Abdullah
authors.affiliation: Cystic Fibrosis/Pulmonary Research and Treatment and Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Olivia S
authors.initials: OS
authors.lastname: Perlmutt
authors.affiliation: Marine Sciences, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Albert
authors.affiliation: Cystic Fibrosis/Pulmonary Research and Treatment and Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: C William
authors.initials: CW
authors.lastname: Davis
authors.affiliation: School of Dentistry, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Roland R
authors.initials: RR
authors.lastname: Arnold
authors.affiliation: Cystic Fibrosis/Pulmonary Research and Treatment and Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Yankaskas
authors.affiliation: Pathology and Laboratory Medicine, Memorial Hospital, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Gilligan
authors.affiliation: Friedrich Loeffler Institut, Institute of Bacterial Infections and Zoonoses, Jena, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Neubauer
authors.affiliation: Cystic Fibrosis/Pulmonary Research and Treatment and Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Randell
authors.affiliation: Cystic Fibrosis/Pulmonary Research and Treatment and Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Boucher
mesh_terms: D019121:Burkholderia Infections / Q000382:microbiology* / Q000473:pathology; D016956:Burkholderia cepacia / Q000502:physiology*; D003470:Culture Media; D003550:Cystic Fibrosis / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D009093:Mucus / Q000737:chemistry* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000502:physiology*
chemical_list: D003470:Culture Media