The two-component sensor response regulator RoxS/RoxR plays a role in Pseudomonas aeruginosa interactions with airway epithelial cells |
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| Authors: | Bryan P. Hurley Andrew L. Goodman Karen L. Mumy Patrick Murphy Stephen Lory Beth A. McCormick |
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| Affiliation: | 1. Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown MA 02129, USA;2. Department of Pediatrics, Harvard Medical School, Boston MA 02115, USA;3. Department Microbiology and Molecular Genetics, Harvard Medical School, Boston MA 02115, USA;4. Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester MA 01655, USA;3. Medical Research Council Centre for Molecular Bacteriology and Infection, Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom;4. Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, United Kingdom;3. From the Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan,;4. the Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan,;5. the Department of Molecular and Cellular Pathobiology and Therapeutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan, and;6. the Laboratory of Disease Biology, Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan;1. MRC Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College London, SW7 2AZ London, United Kingdom;2. Département de Microbiologie Fondamentale, Université de Lausanne, CH-1015 Lausanne, Switzerland;1. MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, 6 Rong Jing Dong Jie, Beijing 100176, P.R. China;2. Warwick Medical School, Warwick University, Coventry CV4 7AL, UK;1. Laboratorio de Biotecnología Microbiana, Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, 58030, Mexico;2. Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad 2001, Col. Chamilpa, Cuernavaca, Morelos, 62210, Mexico;3. Laboratorio de Diferenciación Celular, Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, 58030, Mexico |
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| Abstract: | Pseudomonas aeruginosa is an opportunistic pathogen that infects the lungs of patients with cystic fibrosis causing aberrant and destructive neutrophil (PMN)-dominated inflammation of airways. Interaction of P. aeruginosa with the lung epithelial barrier resulting in trans-epithelial PMN migration likely represents a key event during PMN recruitment. To investigate bacterial factors involved in interactions with lung epithelial cells, a mutant library of two-component system response regulators was evaluated to identify mutants exhibiting defects in the ability to induce PMN trans-epithelial migration. Of forty-eight mutants, five reproducibly demonstrated a reduced PMN trans-epithelial migration response. All five mutants also exhibited a decreased ability to interact with lung epithelial cells. One mutant identified lacks the response regulator gene roxR, which has not previously been reported to be involved regulating factors that facilitate interactions with lung epithelial cells. This finding suggests that RoxR likely regulates genes with relevance to P. aeruginosa mediated lung disease. |
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