Title: Pseudomonas aeruginosa lung infection and biofilm - experience from cystic fibrosis patients

Presenter: Prof. Niels Høiby

University: Department of International Health, Immunology and Microbiology, University of Copenhagen

Time: 9:00-10:00, 11 April, 2011

Venue: A203, Institute of Microbiology, Chinese Academy of Sciences

Introduction: Cystic Fibrosis (CF) is the most common inherited lethal disease in caucasian populations. About 60.000 CF patients are registered in USA, Canada, Europe, Australia and New Zealand, but many more are living in Latin America, the Middle East, Iran, Pakistan and India. The mutations in the CFTR gene lead to malfunction of the chloride channel in CF patients and decreased volume of the paraciliary fluid in the lower respiratory tract and therefore impaired mucociliary clearance of inhaled microbes. This impairment of the non-inflammatory defense mechanism of the respiratory tract leads to recruitment of the inflammatory defense mechanisms dominated by polymorphonuclear leukocytes (PMN) and antibody production. In spite of the inflammatory response and intensive antibiotic therapy, however, infections caused by P. aeruginosa persist and lead to respiratory failure requiring lung transplantation or death of the patients. Adaptive mechanisms of P. aeruginosa explain why this pathogen is able to survive and persist for several decades in the respiratory tract of CF patients in spite of the defense mechanisms of the host and intensive antibiotic therapy. The persistence of chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients is due to biofilm growing mucoid (alginate-producing) strains. A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. In CF lungs the polysaccharide alginate is the major part of the P. aeruginosa biofilm matrix. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and resist phagocytosis and other components of the innate and the adaptive defense system of the body. As a consequence, a pronounced antibody response develops leading to immune complex-mediated chronic inflammation dominated by polymorphonuclear leukocytes. The chronic inflammation is the major cause of the lung tissue damage in CF. Biofilm growth in CF lungs is associated with increased frequency of mutations, slow growth and adaptation of the bacteria to the conditions in the lungs and to the antibiotic therapy. Low bacterial metabolic activity and increase of doubling times of the bacterial cells in CF lungs are responsible for some of the tolerance to antibiotics. Conventional resistance mechanisms such as chromosomal beta-lactamase, up-regulated efflux pumps and mutations of antibiotic target molecules in the bacteria also contribute to the survival of P. aeruginosa biofilms. Biofilm can be prevented by early aggressive antibiotic prophylaxis or therapy and they can be treated by chronic suppressive therapy.