TY - JOUR
T1 - The stringent response and Mycobacterium tuberculosis pathogenesis
AU - Prusa, Jerome
AU - Zhu, Dennis X.
AU - Stallings, Christina L.
N1 - Funding Information:
CLS is supported by a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease Award and National Institutes of Health (NIH) grants GM107544 and AI111696. JP is supported by the National Institute of General Medicine of the National Institutes of Health (NIGMS) Cell and Molecular Biology Training Grant GM007067 and the Stephen I. Morse Graduate Fellowship.
Publisher Copyright:
© FEMS 2018.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - During infection, the host restrains Mycobacterium tuberculosis (Mtb) from proliferating by imposing an arsenal of stresses. Despite this onslaught of attacks, Mtb is able to persist for the lifetime of the host, indicating that this pathogen has substantial molecular mechanisms to resist host-inflicted damage. The stringent response is a conserved global stress response in bacteria that involves the production of the hyperphosphorylated guanine nucleotides ppGpp and pppGpp (collectively called (p)ppGpp). (p)ppGpp then regulates a number of cellular processes to adjust the physiology of the bacteria to promote survival in different environments. Survival in the presence of host-generated stresses is an essential quality of successful pathogens, and the stringent response is critical for the intracellular survival of a number of pathogenic bacteria. In addition, the stringent response has been linked to virulence gene expression, persistence, latency and drug tolerance. In Mtb, (p)ppGpp synthesis is required for survival in low nutrient conditions, long term culture and during chronic infection in animal models, all indicative of a strict requirement for (p)ppGpp during exposure to stresses associated with infection. In this review we discuss (p)ppGpp metabolism and how this functions as a critical regulator of Mtb virulence.
AB - During infection, the host restrains Mycobacterium tuberculosis (Mtb) from proliferating by imposing an arsenal of stresses. Despite this onslaught of attacks, Mtb is able to persist for the lifetime of the host, indicating that this pathogen has substantial molecular mechanisms to resist host-inflicted damage. The stringent response is a conserved global stress response in bacteria that involves the production of the hyperphosphorylated guanine nucleotides ppGpp and pppGpp (collectively called (p)ppGpp). (p)ppGpp then regulates a number of cellular processes to adjust the physiology of the bacteria to promote survival in different environments. Survival in the presence of host-generated stresses is an essential quality of successful pathogens, and the stringent response is critical for the intracellular survival of a number of pathogenic bacteria. In addition, the stringent response has been linked to virulence gene expression, persistence, latency and drug tolerance. In Mtb, (p)ppGpp synthesis is required for survival in low nutrient conditions, long term culture and during chronic infection in animal models, all indicative of a strict requirement for (p)ppGpp during exposure to stresses associated with infection. In this review we discuss (p)ppGpp metabolism and how this functions as a critical regulator of Mtb virulence.
KW - Mycobacteria
KW - Polyphosphate
KW - Rel
KW - Starvation
KW - Stringent response
KW - Tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85050814043&partnerID=8YFLogxK
U2 - 10.1093/femspd/fty054
DO - 10.1093/femspd/fty054
M3 - Short survey
C2 - 29947752
AN - SCOPUS:85050814043
SN - 2049-632X
VL - 76
JO - Pathogens and disease
JF - Pathogens and disease
IS - 5
M1 - fty054
ER -