Evolution of the bacterial nucleosidase PpnN and its relation to the stringent response
Authors:René Lysdal Bærentsen1, Ditlev Egeskov Brodersen1 and Yong Everett Zhang2
doi: 10.15698/mic2019.09.692
Volume 6, pp. 450 to 453, published 16/07/2019.
1 Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.
2 Department of Biology, University of Copenhagen, DK- 2200 Copenhagen N, Denmark.
Keywords:
ppGpp, YgdH, LOG, DUF4478, DUF3412, PAG.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
René Lysdal Bærentsen, Ditlev Egeskov Brodersen and Yong Everett Zhang (2019). Evolution of the bacterial nucleosidase PpnN and its relation to the stringent response. Microbial Cell 6(9): 450-453. doi: 10.15698/mic2019.09.692
© 2019 Bærentsen et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.
Abstract:
In our recent publication (Zhang et al., 2019), we demonstrate an interesting mode of regulation of purine metabolism unique to Proteobacteria. In this microreview, we would like to reflect on the ideas put forward, with special focus on protein domain architecture of the enzyme involved, its orthologues in plants, and the implications of the differential effects observed between binding of the two alarmone molecules, ppGpp (guanosine 3′,5′-bisdiphosphate) and pppGpp (guanosine-5′-triphosphate-3′-diphosphate). In our previous work, we showed that the Escherichia coli nucleotide 5′-monophosphate nucleosidase, PpnN, which is conserved in Proteobacteria, cleaves its preferred substrate, guanosine monophosphate (GMP), at a much higher rate in the presence of both pppGpp and ppGpp (Figure 1A). Structural analysis reveals that binding of pppGpp leads to a conformational change in the protein that exposes its active site, suggesting this is the reason for the observed increase in activity. Finally, point mutation of the alarmone-interacting residues show a defect in binding, resulting in (i) increased basal catalytic activity of PpnN and higher competitive fitness of E. coli in an environment with fluctuating nutrient levels, and (ii) increased bacterial sensitivity towards antibiotics. In contrast, complete loss of the ppnN gene has the inverse effect, i.e. reduced competitive growth and improved antibiotic tolerance. We used these observations to propose a model in which E. coli uses PpnN to balance the need of fitness (fast growth) against tolerance towards antibiotics to improve survival.