Martin Schuster
There has been an explosion in research directed at understanding the mechanisms of how bacteria communicate and cooperate to perform a variety of multicellular behaviors, including biofilm formation. Not until very recently have microbiologists also begun to investigate these behaviors from the perspective of social evolution. Our goal is to integrate mechanistic and evolutionary approaches to investigate communication, also termed quorum sensing (QS), and cooperation in the model bacterium and opportunistic pathogen Pseudomonas aeruginosa. P. aeruginosa communicates via diffusible acyl-homoserine lactone signals to coordinate the expression of hundreds of genes, many of which encode extracellular virulence factors. On a mechanistic level, we have utilized a variety of different approaches, including transcriptomics, ChIP-chip, and mutagenesis, to identify directly and indirectly regulated genes, and to characterize additional regulators of the QS system. With respect to sociobiology, we have utilized in vitro evolution and analysis of natural P. aeruginosa populations to gain insight into the propensity of cheating in bacterial populations, which is a threat common to social systems across all domains of life. We identified variants that ceased production of shared extracellular factors and took advantage of their production by the group. The existence of these cheaters demonstrates the sociality of microbes, and provides a compelling resolution to the long-standing paradox in P. aeruginosa pathogenesis that although QS is required for infection in animal models, QS-deficient variants are commonly associated with infections. In addition to cheating, our evolution-in-a-test-tube experiment also revealed a mechanism of cheater control. Before cheating became detrimental to the population, a novel type of cooperator with superior fitness had evolved from a cheating ancestor. Experiments are underway to define the underlying mechanism. As an extension of our own work, an attempt will be made to compare and contrast current mechanistic and sociobiological views on biofilm formation. A combination of both perspectives appears necessary to build a complete model of biofilm formation and guide appropriate treatment strategies.
