Revisiting the host as a growth medium

Key Points The ability of a pathogen to cause disease relies on its ability to acquire nutrients in vivo . This Review revisits the concept of the host as a growth medium during infection and outlines the potential of this experimental approach for development of new therapeutics. The carbon source can influence the ability of a pathogen to evade the immune system. Neisseria meningitidis preferentially uses a carbon source which has degradation products that feed directly into the biosynthesis of compounds important for immune evasion. The available carbon source affects site-specific colonization, or tissue tropism, by certain pathogens. Unlike enterohaemorrhagic Escherichia coli (EHEC) strains, uropathogenic E. coli (UPEC) strains can colonize the urinary tract. The ability of UPEC to catabolize D -serine, excreted as a urinary waste product, might help to define this tropism. Carbon resource partitioning is a method used to avoid competition with other organisms. Aggregatibacter actinomycetemcomitans , a slow-growing opportunistic pathogen that is found in the human mouth, uses a non-optimal carbon source that is produced as a waste product by prevalent and fast-growing oral streptococci. Bacteria communicate using diverse chemical signals, and carbon source metabolism can influence production and dissemination of these signals. Pseudomonas aeruginosa responds to aromatic amino acids in cystic fibrosis sputum and increases production of a cell–cell communication signal that is important for interspecies competition and virulence. Many infection sites, as bacterial growth media, remain undefined, and for many pathogens the in vivo carbon source is not known. Much work remains to be done to elucidate bacterial carbon metabolism during infection. What makes the human body a good growth medium for bacterial pathogens? In this Review, Brown, Palmer and Whiteley outline how the host growth environment affects disease and discuss the potential for targeting host metabolic pathways for therapeutic development. The ability of the human body to play host to bacterial pathogens has been studied for more than 200 years. Successful pathogenesis relies on the ability to acquire the nutrients that are necessary for growth and survival, yet relatively little is understood about the in vivo physiology and metabolism of most human pathogens. This Review discusses how in vivo carbon sources can affect disease and highlights the concept that carbon metabolic pathways provi