Microbial metabolism - back in fashion
Science and fashion share some common traits, including a propensity to rediscover old ideas/themes and re-examine them in a new light. Such is the case with cellular metabolism. After the renaissance in metabolic studies during the mid-20th century, when many University science and medical departments were full of research groups working on enzymes and metabolic pathways, interest in cellular metabolism receded - overtaken by the revolutions in genomics, cell biology, the rise of the ‘omics’ technologies and perhaps a perception that metabolism was primarily a housekeeping process and a bit boring. However, we are now experiencing an impressive revival of interest in cellular metabolism. This has been driven, in part, by an appreciation that the metabolic activities of all cells are intimately tailored to the specific needs and functions of that cell or tissue and that detailed information on cellular metabolism is critical for understanding cellular development and disease mechanisms. It is also clear that there are major gaps in our understanding of how cellular metabolism is regulated in vivo. At the same time there have been impressive advances in our ability to measure metabolic processes in vivo, and to integrate ‘omics’ data in order to understand the multiple levels of regulation of metabolism.
The revival in interest in metabolism has been particularly apparent to those of us who work on microbial pathogens. These organisms are in a constant war with their host over access to carbon sources and nutrients and, like other cells, need to tailor their metabolism to fulfill particular tasks, such as the synthesis of specialized virulence factors or the maintenance of their energy/redox state in inhospitable environments. This battle is likely to have played a key role in defining microbial growth strategies and the range of host niches that each pathogen can occupy. The renewed interest in microbial metabolism has been prompted by the imperative (and increased funding opportunities in some areas) to identify new drug targets and/or understand the mechanism of action of existing drugs, as well as the realization that, in most cases, direct information on nutrient levels and pathogen metabolism in vivo is missing. Moreover, despite some of these pathogens’ being amongst the most intensively studied organisms in biology, we still do not know what the majority of their genes do, although it is reasonable to suggest that many are directly or indirectly involved in regulating metabolism. On the other side of the ledger, we are only just beginning to explore how intracellular and extracellular pathogens manipulate the metabolism of their host in order to create a more hospitable metabolic niche. Some of the open questions that come to mind when considering the role of metabolism in host-pathogen interactions are as follows.