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(p)ppGpp and Its Role in Bacterial Persistence: New Challenges.

Olga Pacios1, Lucia Blasco1, Inés Bleriot1

  • 1Microbiology Department, Research Institute Biomedical A Coruña (INIBIC), Hospital A Coruña (CHUAC), University of A Coruña (UDC), A Coruña, Spain.

Antimicrobial Agents and Chemotherapy
|July 29, 2020
PubMed
Summary

Bacterial persistence, a key factor in antibiotic failure, is linked to the stringent response and magic spot signaling molecule (p)ppGpp. Targeting (p)ppGpp offers a promising strategy for developing novel antipersistence therapies.

Keywords:
(p)ppGppTA systemspersistenceslow growth

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Bacterial Pathogenesis

Background:

  • Antibiotic failure is often caused by bacterial persistence and tolerance, collectively termed the 'persistent phenotype'.
  • Toxin-antitoxin (TA) modules and guanosine pentaphosphate/tetraphosphate [(p)ppGpp], or 'magic spot', are critical molecular mechanisms underlying persistence.
  • (p)ppGpp acts as a stress alarmone, orchestrating the stringent response in bacteria.

Purpose of the Study:

  • To clarify the complex and sometimes contradictory literature on the role of (p)ppGpp in bacterial persistence.
  • To provide new insights into the relationship between the stringent response and bacterial persistence.
  • To review emerging therapeutic strategies targeting (p)ppGpp for antipersistence treatments.

Main Methods:

  • Literature review and synthesis of existing research on (p)ppGpp, stringent response, and bacterial persistence.
  • Analysis of molecular mechanisms involving toxin-antitoxin modules and (p)ppGpp signaling.
  • Exploration of current and potential therapeutic interventions targeting (p)ppGpp.

Main Results:

  • The stringent response, regulated by (p)ppGpp, is involved in bacterial adaptation to various stresses, pathogenesis, and antibiotic tolerance.
  • (p)ppGpp accumulation occurs not only during starvation but also in response to diverse environmental cues like pH, oxygen, and temperature.
  • The review consolidates understanding of (p)ppGpp's multifaceted role in bacterial persistence.

Conclusions:

  • The stringent response and (p)ppGpp signaling are integral to bacterial persistence, contributing significantly to antibiotic failure.
  • Targeting (p)ppGpp pathways presents a promising avenue for developing novel antipersistence agents.
  • Further research into (p)ppGpp-mediated mechanisms could lead to effective strategies against persistent bacterial infections.