The effect of concentrated cell-free extracellular material from stationary-phase cultures of Burkholderia cepacia 10661 and Pseudomonas aeruginosa PAO1 on virulence factor production in B. cepacia was assessed. While increasing concentrations of the B. cepacia exoproduct caused a slight increase in siderophore, lipase, and protease production in the producing organism, a significant increase in productivity was observed for all three virulence factors with the addition of the PAO1 exoproduct. Moreover, the addition of the exoproduct from a strain of P. aeruginosa producing reduced amounts of autoinducer caused only a slightly greater response than that of the control. Both B. cepacia 10661 and P. aeruginosa PAO1, along with two matched clinical isolates of both organisms obtained from a cystic fibrotic patient, were shown to produce variable amounts of three different types of autoinducer. The potential for interspecies signalling in microbial pathogenicity is discussed.Burkholderia cepacia, formerly known as Pseudomonas cepacia, is now recognized as an important opportunistic agent of human disease (6,8). In particular, it has received a great deal of attention owing to its increasing association with fatal pulmonary infections in patients with cystic fibrotic (CF) lung disease (9, 13). Clinically, B. cepacia colonization of CF patients can result in an asymptomatic carriage, a slow and continuous decline in lung function, or third, a rapid deterioration of the lung accompanied by fever, necrotizing pneumonia, and in some cases, bacteremia (6, 9). This third syndrome is not observed with other CF pathogens. Generally, it has been noted that B. cepacia colonizes the lung after infection by other microorganisms (24,25). Indeed, in a recent survey of the population with CF lung disease in Greater Manchester, England, only 3.3% of patients were colonized exclusively with B. cepacia (11). Instead, over 80% of the patients were cocolonized with P. aeruginosa. Whereas P. aeruginosa produces a panoply of virulence factors which play an active role in the organism's pathogenicity (7,26), little is known about the pathophysiology of B. cepacia (5,14). Isolated strains of B. cepacia are variable in their abilities to produce hemolysins, lipase and protease (5), exopolysaccharide (2, 17), and ironchelating siderophores (12, 21) in vitro. Consequently, there has been no direct correlation with any of these virulence factors to the organism's pathogenic status in vivo. However, a novel possibility might be the active coaggregation of B. cepacia and P. aeruginosa in the lungs, whereby one species synergistically enhances the virulence determinants of the other. To this effect, the enhancement of B. cepacia attachment to different surfaces by P. aeruginosa exoproducts has been demonstrated (1, 18).It is now recognized that individual cells within a multicellular system can both generate signals and respond to those produced by the surrounding cells, providing a basis for cells to change in response to prevailing environmental...