title: Sugar administration is an effective adjunctive therapy in the treatment of Pseudomonas aeruginosa pneumonia.
abstract: Treatment of acute and chronic pulmonary infections caused by opportunistic pathogen Pseudomonas aeruginosa is limited by the increasing frequency of multidrug bacterial resistance. Here, we describe a novel adjunctive therapy in which administration of a mix of simple sugars-mannose, fucose, and galactose-inhibits bacterial attachment, limits lung damage, and potentiates conventional antibiotic therapy. The sugar mixture inhibits adhesion of nonmucoid and mucoid P. aeruginosa strains to bronchial epithelial cells in vitro. In a murine model of acute pneumonia, treatment with the sugar mixture alone diminishes lung damage, bacterial dissemination to the subpleural alveoli, and neutrophil- and IL-8-driven inflammatory responses. Remarkably, the sugars act synergistically with anti-Pseudomonas antibiotics, including β-lactams and quinolones, to further reduce bacterial lung colonization and damage. To probe the mechanism, we examined the effects of sugars in the presence or absence of antibiotics during growth in liquid culture and in an ex vivo infection model utilizing freshly dissected mouse tracheas and lungs. We demonstrate that the sugar mixture induces rapid but reversible formation of bacterial clusters that exhibited enhanced susceptibility to antibiotics compared with individual bacteria. Our findings reveal that sugar inhalation, an inexpensive and safe therapeutic, could be used in combination with conventional antibiotic therapy to more effectively treat P. aeruginosa lung infections.
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Iwona
authors.initials: I
authors.lastname: Bucior
authors.forename: Jason
authors.initials: J
authors.lastname: Abbott
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Song
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
authors.forename: Joanne N
authors.initials: JN
authors.lastname: Engel
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001422:Bacterial Adhesion / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D002241:Carbohydrates / Q000008:administration & dosage*; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D005643:Fucose / Q000008:administration & dosage; D005690:Galactose / Q000008:administration & dosage; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D055370:Lung Injury / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008358:Mannose / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011134:Polysaccharides / Q000008:administration & dosage; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D002241:Carbohydrates; D016209:Interleukin-8; D011134:Polysaccharides; D005643:Fucose; D008358:Mannose; D005690:Galactose
keywords: Pseudomonas aeruginosa; antibiotics; microbial pathogenesis; pneumonia; therapeutics