Survival of the Fittest: The Relationship of (p)ppGpp With Bacterial Virulence.

Shivani Kundra,Cristina Colomer-Winter,José A Lemos

doi:10.3389/fmicb.2020.601417

Abstract

The signaling nucleotide (p)ppGpp has been the subject of intense research in the past two decades. Initially discovered as the effector molecule of the stringent response, a bacterial stress response that reprograms cell physiology during amino acid starvation, follow-up studies indicated that many effects of (p)ppGpp on cell physiology occur at levels that are lower than those needed to fully activate the stringent response, and that the repertoire of enzymes involved in (p)ppGpp metabolism is more diverse than initially thought. Of particular interest, (p)ppGpp regulation has been consistently linked to bacterial persistence and virulence, such that the scientific pursuit to discover molecules that interfere with (p)ppGpp signaling as a way to develop new antimicrobials has grown substantially in recent years. Here, we highlight contemporary studies that have further supported the intimate relationship of (p)ppGpp with bacterial virulence and studies that provided new insights into the different mechanisms by which (p)ppGpp modulates bacterial virulence.

Highlights

In response to changes in the surrounding environment, bacteria utilize a variety of sophisticated sensory mechanisms that reprogram cell physiology to facilitate adaptation to the new environment
In addition to the expression of classic virulence factors such as toxins, capsule and fimbriae, contemporary investigations into the mechanisms of bacterial pathogenesis revealed that core cellular processes associated with metabolism and stress tolerance can be or even more critical to bacterial pathogenesis
The picture that emerges from recent studies is that the role of either the stringent response (SR) or basal levels of (p)ppGpp to bacterial virulence depends on the lifestyle and metabolic versatility of each organism

Summary

Introduction

In response to changes in the surrounding environment, bacteria utilize a variety of sophisticated sensory mechanisms that reprogram cell physiology to facilitate adaptation to the new environment. The contribution of (p)ppGpp and the SR to staphylococcal virulence was first demonstrated in a synthetase-dead/hydrolaseactive Rel mutant strain (relsyn), where loss of RelSa synthetase activity significantly attenuated S. aureus virulence in a mouse model of kidney infection (Geiger et al, 2010).

Results

Conclusion