title: Pseudomonas aeruginosa alginate promotes Burkholderia cenocepacia persistence in cystic fibrosis transmembrane conductance regulator knockout mice.
abstract: Pseudomonas aeruginosa, a major respiratory pathogen in cystic fibrosis (CF) patients, facilitates infection by other opportunistic pathogens. Burkholderia cenocepacia, which normally infects adolescent patients, encounters alginate elaborated by mucoid P. aeruginosa. To determine whether P. aeruginosa alginate facilitates B. cenocepacia infection in mice, cystic fibrosis transmembrane conductance regulator knockout mice were infected with B. cenocepacia strain BC7 suspended in either phosphate-buffered saline (BC7/PBS) or P. aeruginosa alginate (BC7/alginate), and the pulmonary bacterial load and inflammation were monitored. Mice infected with BC7/PBS cleared all of the bacteria within 3 days, and inflammation was resolved by day 5. In contrast, mice infected with BC7/alginate showed persistence of bacteria and increased cytokine levels for up to 7 days. Histological examination of the lungs indicated that there was moderate to severe inflammation and pneumonic consolidation in isolated areas at 5 and 7 days postinfection in the BC7/alginate group. Further, alginate decreased phagocytosis of B. cenocepacia by professional phagocytes both in vivo and in vitro. P. aeruginosa alginate also reduced the proinflammatory responses of CF airway epithelial cells and alveolar macrophages to B. cenocepacia infection. The observed effects are specific to P. aeruginosa alginate, because enzymatically degraded alginate or other polyuronic acids did not facilitate bacterial persistence. These observations suggest that P. aeruginosa alginate may facilitate B. cenocepacia infection by interfering with host innate defense mechanisms.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Sangbrita S
authors.initials: SS
authors.lastname: Chattoraj
authors.forename: Rachana
authors.initials: R
authors.lastname: Murthy
authors.forename: Shyamala
authors.initials: S
authors.lastname: Ganesan
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Goldberg
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
authors.forename: Umadevi S
authors.initials: US
authors.lastname: Sajjan
mesh_terms: D000464:Alginates / Q000378:metabolism*; D000818:Animals; D019117:Burkholderia / Q000254:growth & development*; D019121:Burkholderia Infections / Q000382:microbiology*; D015169:Colony Count, Microbial; D003550:Cystic Fibrosis / Q000150:complications* / Q000382:microbiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency*; D016207:Cytokines / Q000032:analysis; D020723:Glucuronic Acid / Q000378:metabolism; D006603:Hexuronic Acids / Q000378:metabolism; D006651:Histocytochemistry; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008853:Microscopy; D011550:Pseudomonas aeruginosa / Q000378:metabolism*
chemical_list: D000464:Alginates; D016207:Cytokines; D006603:Hexuronic Acids; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D020723:Glucuronic Acid