Lung infection with alginate-producing, mucoid Pseudomonas aeruginosa in cystic fibrosis

Progressive pulmonary insufficiency is the major cause of morbidity and mortality in patients with the inherited disease cystic fibrosis. The basic defect involves a disturbed ion transport across cells, but it is not known how this leads to the airways becoming highly susceptible to recurrent respiratory tract infection with S. aureus, H. influenzae and P. aeruginosa as the dominating pathogens. P. aeruginosa is not a primary pathogen in CF and some degree of lung damage generally has taken place before colonization begins at approximately 10 years of age. Cross-infection occurs and the incidence of P. aeruginosa infection can be reduced by interrupting person-to-person spread. P. aeruginosa infection is a chronic infection that is never permanently eradicated. However, intensive antipseudomonal chemotherapy has contributed to improved survival rates. 90% of patients remain alive more than 10 years after onset of chronic P. aeruginosa and, on an average, they can maintain an almost unchanged lung function during that period. Diagnosis of chronic infection rests on bacteriological examination and demonstration of a specific antibody response. Immunological assays to detect an early antibody response were developed. It is characteristic, but not specific for CF, that chronic lung infection is caused by alginate producing mucoid P. aeruginosa. Alginate biosynthesis is under complex genetic control and possibly regulated by environmental factors. Alginate was purified from mucoid P. aeruginosa and characterized and it was shown to be immunologically heterogenous. It is generally assumed that the infection begins with strains that are nonmucoid, but serological analysis show that these strains probably also produce the mucoid substance, alginate, in vivo. Patients infected with mucoid strains demonstrate a significantly higher antibody response to all P. aeruginosa antigens and have a lower lung function when compared to patients infected with nonmucoid strains. Despite the pronounced humoral antibody response efficient immune clearance of P. aeruginosa does not occur. Mucoid P. aeruginosa are organisms that are deficient in most of the classical virulence factors. In vivo it grows in a protected biofilm as mucoid microcolonies, where bacteria are enmeshed in a loosely bound, highly hydrated extracellular matrix of alginate. Purified alginate was shown to inhibit chemotaxis of neutrophil leukocytes and unable to activate complement. A deficient SIgA antibody response to alginate has been observed in bronchial secretions and it was hypothesized to be associated with the epithelial transport defect.(ABSTRACT TRUNCATED AT 400 WORDS)