title: Pseudomonas aeruginosa adaptation in the nasopharyngeal reservoir leads to migration and persistence in the lungs.
abstract: Chronic bacterial infections are a key feature of a variety of lung conditions. The opportunistic bacterium, Pseudomonas aeruginosa, is extremely skilled at both colonizing and persisting in the airways of patients with lung damage. It has been suggested that the upper airways (including the paranasal sinuses and nasopharynx) play an important role as a silent reservoir of bacteria. Over time, P. aeruginosa can adapt to its niche, leading to increased resistance in the face of the immune system and intense therapy regimes. Here we describe a mouse inhalation model of P. aeruginosa chronic infection that can be studied for at least 28 days. We present evidence for adaptation in vivo, in terms of genotype and phenotype including antibiotic resistance. Our data suggest that there is persistence in the upper respiratory tract and that this is key in the establishment of lung infection. This model provides a unique platform for studying evolutionary dynamics and therapeutics.
authors.affiliation: 1] Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK [2].
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Fothergill
authors.affiliation: 1] Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK [2].
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Neill
authors.affiliation: Institute for Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Loman
authors.affiliation: 1] Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK [2].
authors.forename: Craig
authors.initials: C
authors.lastname: Winstanley
authors.affiliation: 1] Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK [2].
authors.forename: Aras
authors.initials: A
authors.lastname: Kadioglu
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D018441:Biofilms / Q000254:growth & development; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009305:Nasopharynx / Q000382:microbiology / Q000473:pathology; D010256:Paranasal Sinuses / Q000382:microbiology / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins