Identification of Staphylococcus aureus genes involved in the formation of structured macrocolonies

The human pathogen Staphylococcus aureus causes difficult-to-eradicate biofilm-associated infections that generally become chronic. Understanding the genetic regulation of biofilm formation in S. aureus is central to a precise definition of the conditions and genes involved in development of chronic biofilm-associated infections. Biofilm-related genes have been detected by comparing mutants using the classical submerged biofilm formation assay, in which cells adhere to the bottom of a well containing culture medium. We recently developed an alternative biofilm formation model for S. aureus, based on macrocolony formation on agar plates, comparable to an assay used to study biofilm formation in a few other bacterial species. As organism features are the result of environmental conditions as well as of genes, we used a genome-wide collection of transposon-mapped mutants in this macrocolony assay to seek S. aureus developmental genes and pathways not identified by the classical biofilm formation assay. We identified routes related to glucose and purine metabolism and clarified their regulatory link to macrocolony formation. Our study demonstrates that formation of microbial communities must be correlated to specific growth conditions, and the role of metabolism must be considered in S. aureus biofilm formation and thus, in the development of chronic infections.