The role of the microcolony mode of growth in the pathogenesis of Pseudomonas aeruginosa infections

Abstract

In nature Pseudomonas aeruginosa grows in two modes, the mobile "swarmer" cell and the glycocalyx-enclosed microcolony. The microcolony mode is numerically dominant perhaps because it provides adhesion in a favorable niche and protection from bacteriophages and phagocytic predators. When this organism colonizes the compromised human host, a broad spectrum of different types of infection is produced, ranging from asymptomatic persistent cystitis to the overwhelming bacteremia seen in neutropenic patients. These infections differ radically both in their degree of toxicity and invasiveness and in their susceptibility to control with specific antibodies and/or antibiotics. These differences may reflect the degree to which intact host defense mechanisms force the bacteria to adopt the defensive, microcolony mode of growth. As examples, the nearly intact host defense mechanisms and vigorous immune response of patients with cystic fibrosis force P. aeruginosa in pulmonary infections into a demonstrably cryptic, microcolony mode of growth that allows its persistence in the face of specific antibodies and antibiotics but limits its toxic activity and its dissemination. In contrast, the ruined defense mechanisms of burned skin allow the spread of bacteria in the mobile mode; toxic effects are seen in neighboring tissues, and a mixed mobile-microcolony reservoir population, whose mobile members can subsequently invade the circulatory system, is built up in the burned tissue. Thus, it is important to define the mode of bacterial growth in each type of P. aeruginosa infection and, where the microcolony mode is predominant, to understand the chemistry of the enveloping exopolysaccharide in order to limit its synthesis and/or facilitate its penetration by antibodies and antibiotics.