The delicate balance of bacterial purine homeostasis
Anne Grove
Abstract
The purines guanine and adenine are building blocks of DNA and RNA, and they are required for processes such as signal transduction and energy metabolism. During normal bacterial growth, a balance is maintained between their biosynthesis, interconversion, and degradation. Disruption of purine homeostasis has been primarily investigated in humans, where several disorders have been described that are associated with defects in purine metabolic enzymes. However, an imbalance in purine levels also adversely affects bacteria, for instance hindering growth, altering virulence, and imposing susceptibility to antibiotics. This review summarizes purine metabolic pathways, highlighting notable distinctions between species, particularly pertaining to salvage and degradation. The direct link between purine homeostasis and the synthesis of purine-based secondary messengers such as cyclic-di-GMP is discussed, as these messengers in turn have profound effects on bacterial physiology. The unique roles of the purine catabolite urate in terms of its possible role as an antioxidant, as a host-derived inducer of virulence gene expression, and as a substrate for bacteria inhabiting the mammalian gut are also considered. Because of the importance of de novo purine biosynthesis, particularly in a nutrient-limited host environment, purine biosynthetic enzymes and associated transcriptional regulators present as promising targets for antibacterial interventions.