Lean and Mean: Dual Control of Bacterial Virulence by the "Stress Alarmone" ppGpp and Quorum Sensing.
It has been known for around two decades now that the production of virulence determinants in many bacteria is controlled by a mechanism of population cell density titration known as "quorum sensing" (QS). It turns out that at low population cell densities, an RNA-binding molecule called RsmA is made. The RsmA molecule binds virulence factor transcripts and targets them for degradation. In this way, virulence is suppressed. In contrast, once the population becomes quorate, expression of the rsmA gene is turned off. In principle, this should de-repress virulence. However, it doesn’t. This is because RsmA is only slowly turned over in the cell. To circumvent this problem, transcription of a gene encoding a small RNA (rsmB) is activated. The rsmB RNA binds and sequesters RsmA, thereby effectively “mopping up” free RsmA. This gives rise to a concerted burst of virulence factor production – just what is needed in order to mount a successful attack the host. The question is, “what regulates rsmB expression?” We recently showed that rsmB expression is primarily-dependent upon accumulation of the "stress alarmone", ppGpp, and that QS and ppGpp form an integrated coincidence circuit which allows the cells to simultaneously monitor the population cell density and nutrient availability. In the proposed project, the tools of biochemistry and molecular biology will be used to work out how ppGpp stimulates rsmB expression: which gene products are involved and how do they interact.
- Steven D. Bowden, Alison Eyres, Jade C.S. Chung, Rita E. Monson, Arthur Thompson, George P.C. Salmond, David R. Spring and Martin Welch. Virulence in Pectobacterium atrosepticum is regulated by a coincidence circuit involving quorum sensing and the stress alarmone, (p)ppGpp. Molecular Microbiology (2013) In Press.
- Steven D. Bowden, Nicola Hale, Jade C.S. Chung, James T. Hodgkinson, David R. Spring and Martin Welch. Surface swarming motility by Pectobacterium atrosepticum is a latent phenotype that requires O antigen and is regulated by quorum sensing. Microbiology (2013) In Press.
- Warren R. J. D. Galloway, James T. Hodgkinson, Steven D. Bowden, Martin Welch, and David R Spring. Small molecule modulation of quorum sensing in Gram-negative bacteria. ACS Chemical Reviews, 11 : 28-67 (2011).