Pseudomonas aeruginosa is a biofilm model organism. It is also a dangerous nosocomial pathogen notorious for its chronic infections and their intrinsic ability to resist various antibiotics. It is an extremely metabolically versatile organism capable of forming prolific biofilms on abiotic surfaces such as catheters, contact lens, and other implanted device, as well as biotic surfaces such as chronic wounds, lungs of patients with cystic fibrosis, and urinary tracts. P. aeruginosa can express a wide variety of virulence factors that it can use against infecting host or neighboring species occupying a niche in its close proximity. P. aeruginosa also expresses a range of biofilm-associated factors including adhesive proteins and multiple types of extracellular polysaccharides. The complex regulation systems that control the expression of these factors are important aspects of P. aeruginosa biology.
Post-transcriptional regulator RsmA
One of the major central regulators for P. aeruginosa responsible for reciprocal expression of virulence and biofilm factors is an RNA-binding post-transcriptional regulator RsmA (Regulator of Secondary Metabolites). Based on phenotypic assays, RsmA appears to be associated with motility, biofilms, toxin production, and quorum sensing. In our lab, we are particularly interested in the RsmA-mediated repression of biofilm extracellular polysaccharides PEL and PSL. We are investigating the mechanisms which lead to downregulations of protein translation by inducing RNA secondary structures and blocking ribosome access upon RsmA-mRNA ribonucleoprotein complex formation.
c-di-GMP feed-forward regulation of PSL polysaccharides
Secondary messenger molecule c-di-GMP is typically a positive regulator of biofilm-associated factors across many bacterial species. In P. aeruginosa, c-di-GMP regulates biofilm polysaccharides PEL and PSL, and adhesins such as CdrA, as well as downregulating flagellar motility. Recently, we discovered that the expression of PSL itself can trigger the increase of intracellular c-di-GMP levels, thus featuring a unique feed-forward regulatory loop of c-di-GMP and PSL. We are investigating how PSL stimulates the activity of diguanylate cyclases that are responsible for synthesizing c-di-GMP.
Social evolutionary roles of biofilm polysaccharides PEL and PSL
Like many species, P. aeruginosa expresses multiple extracellular polysaccharides to build their biofilm matrix. These polysaccharides are often regarded as common shared goods that all populations within a biofilm community can utilize. Multiple studies using computer simulations of biofilm formation set their parameters with this assumption. However, this hypothesis is poorly tested in empirical experimentations. Our observations paint a somewhat different picture where PSL is social, but non-cheatable goods, whereas PEL is entirely private goods. Two polysaccharides from the same strain can have such distinct social traits, and this prompts the necessity to test other biofilm components in P. aeruginosa as well as other species expressing different sets of molecules for their biofilm matrices.
