A murine model of chronic mucosal colonization by Pseudomonas aeruginosa

Abstract

Chronic mucosal colonization by Pseudomonas aeruginosa is an integral part of the pathologic process associated with disease due to infection with this organism. We have adapted the streptomycin-treated murine model of chronic mucosal colonization by enteric pathogens to study colonization by P. aeruginosa. Mice first received 1 mg of streptomycin per ml of drinking water for 2 to 5 days and then ingested 107 CFU of P. aeruginosa per ml of drinking water for a minimum of 5 days. The result of this regimen was chronic mucosal colonization with P. aeruginosa for up to 10 weeks, which was determined by fecal cultures and confirmed by culture of the intestines after killing of the experimental animals. Bacterial counts were highest in the cecum and colon, with some evidence for extraintestinal bacterial translocation as well. Use of P. aeruginosa mutants deficient in the production of colonization factors such as pili and those dependent on the rpoN gene product resulted in a lower level of chronic colonization. Immune responses to type-specific lipopolysaccharide, pili, and flagellar antigens were measured, and increases in both serum and intestinal antibodies were usually elicited when a strain elaborated a given antigen. This model represents an easy method of routinely achieving chronic mucosal colonization by P. aeruginosa and should prove useful for the study of both bacterial virulence factors and host responses associated with this infectious process.

Microbial Pathogenesis in Cystic Fibrosis: Pulmonary Clearance of MucoidPseudomonas aeruginosaand Inflammation in a Mouse Model of Repeated Respiratory Challenge

“…Several useful models of acute and forced chronic P. aerugi-nosa infection have been described in normal, neutropenic, neonatal, or burned mice and in other animals (5,8,10,21,38,47,(49)(50)(51)53). Recently, an aerosol model of respiratory infections with Staphylococcus aureus and Burkholderia cepacia has been developed in the CFTR m1HGU transgenic mouse with a mild defect in the CFTR gene (11).…”

Role of Pseudomonas aeruginosa pili in acute pulmonary infection

“…These gene products may not be expressed during the chronic stage of infection which eventually characterizes P. aeruginosa infections in CF patients. A number of animal models have been developed specifically to look at the unusual interactions of chronic P. aeruginosa infection and the CF lung, including those described by Cash et al (1), Woods et al (20), and Pier et al (10). However, fewer data are available characterizing the factors of P. aeruginosa associated with initial infection of the respiratory tract.…”

Potential of preventing Pseudomonas aeruginosa lung infections in cystic fibrosis patients: Experimental studies in animals

“…It has been claimed that the high proteolytic activity found in CF lung exudates is the result of an increased production of elastase (197) and, according to Goldstein and Doring (93, an imbalance between PMN elastase and their inhibitors, since al-PI was inactivated in sputum by elastase (95). Bacterial colonization of the mucosal surface of the upper respiratory tract is the initial step leading to chronic lung infection (219). It is uncertain, however, which virulence factors are most important for initial colonization.…”