Abstract
(p)ppGpp is at the core of global bacterial regulation as it controls growth, the most important aspect of life. It would therefore be expected that at least across a species the intrinsic (basal) levels of (p)ppGpp would be reasonably constant. On the other hand, the historical contingency driven by the selective pressures on bacterial populations vary widely resulting in broad genetic polymorphism. Given that (p)ppGpp controls the expression of many genes including those involved in the bacterial response to environmental challenges, it is not surprising that the intrinsic levels of (p)ppGpp would also vary considerably. In fact, null mutations or less severe genetic polymorphisms in genes associated with (p)ppGpp synthesis and hydrolysis are common. Such variation can be observed in laboratory strains, in natural isolates as well as in evolution experiments. High (p)ppGpp levels result in low growth rate and high tolerance to environmental stresses. Other aspects such as virulence and antimicrobial resistance are also influenced by the intrinsic levels of (p)ppGpp. A case in point is the production of Shiga toxin by certain E. coli strains which is inversely correlated to (p)ppGpp basal level. Conversely, (p)ppGpp concentration is positively correlated to increased tolerance to different antibiotics such as β-lactams, vancomycin, and others. Here we review the variations in intrinsic (p)ppGpp levels and its consequences across the E. coli species.
Highlights
Specialty section: This article was submitted to Microbial Physiology and Metabolism, a section of the journal Frontiers in Microbiology
The grip of (p)ppGpp on growth rate is achieved mainly through an effective inhibition of stable RNA synthesis during amino acid starvation and other nutritional stresses in a process that became known as the stringent control (Cashel and Gallant, 1968; Potrykus and Cashel, 2008; Potrykus et al, 2011)
Bacteria that display intrinsic high levels of (p)ppGpp are more resistant to environmental stresses either because they express high levels of RpoS or because (p)ppGpp directly stimulates the transcription of other genes related to stress protection
Summary
Specialty section: This article was submitted to Microbial Physiology and Metabolism, a section of the journal Frontiers in Microbiology. The relA1 mutant displays lower ppGpp basal level than the relA+ strain (Lagosky and Chang, 1980) and does not accumulate (p)ppGpp in response to amino acid starvation. The recombinant strains displayed all the hallmarks of the previously analyzed spoT mutations, namely slower growth rate, high levels of the sigma factor RpoS (coordinator of the general stress response) and high resistance to environmental stresses (see below).
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