Bacterial l-leucine catabolism as a source of secondary metabolites

The sputum (mucus) layer of the cystic fibrosis (CF) lung is a complex substrate that provides Pseudomonas aeruginosa with carbon and energy to support high-density growth during chronic colonization. Unfortunately, the CF lung sputum layer has been difficult to mimic in animal models of CF disease, and mechanistic studies of P. aeruginosa physiology during growth in CF sputum are hampered by its complexity. In this study, we performed chromatographic and enzymatic analyses of CF sputum to develop a defined, synthetic CF sputum medium (SCFM) that mimics the nutritional composition of CF sputum. Importantly, P. aeruginosa displays similar phenotypes during growth in CF sputum and in SCFM, including similar growth rates, gene expression profiles, carbon substrate preferences, and cell-cell signaling profiles. Using SCFM, we provide evidence that aromatic amino acids serve as nutritional cues that influence cell-cell signaling and antimicrobial activity of P. aeruginosa during growth in CF sputum.

Metabolically versatile free-living bacteria have global regulation systems that allow cells to selectively assimilate a preferred compound among a mixture of several potential carbon sources. This process is known as carbon catabolite repression (CCR). CCR optimizes metabolism, improving the ability of bacteria to compete in their natural habitats. This review summarizes the regulatory mechanisms responsible for CCR in the bacteria of the genus Pseudomonas, which can live in many different habitats. Although the information available is still limited, the molecular mechanisms responsible for CCR in Pseudomonas are clearly different from those of Enterobacteriaceae or Firmicutes. An understanding of the molecular mechanisms underlying CCR is important to know how metabolism is regulated and how bacteria degrade compounds in the environment. This is particularly relevant for compounds that are degraded slowly and accumulate, creating environmental problems. CCR has a major impact on the genes involved in the transport and metabolism of nonpreferred carbon sources, but also affects the expression of virulence factors in several bacterial species, genes that are frequently directed to allow the bacterium to gain access to new sources of nutrients. Finally, CCR has implications in the optimization of biotechnological processes such as biotransformations or bioremediation strategies.