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Elucidating the role of (p)ppGpp in mycobacterial persistence against antibiotics.

  • Bhaskar A Laboratory of Microbiology and Microtechnology, School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.
  • De Piano C Laboratory of Microbiology and Microtechnology, School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.
  • Gelman E Laboratory of Microbiology and Microtechnology, School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.
  • McKinney JD Laboratory of Microbiology and Microtechnology, School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.
  • Dhar N Laboratory of Microbiology and Microtechnology, School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.
  • 2018-08-10
Published in:
  • IUBMB life. - 2018
Mycobacterium
antibiotics
persistence
persister
polyphosphates
ppGpp
stringent response
Anti-Bacterial Agents
Drug Resistance, Bacterial
Guanosine Pentaphosphate
Humans
Mycobacterium smegmatis
Phosphotransferases (Phosphate Group Acceptor)
Tuberculosis
English Bacterial persistence, the ability of bacteria to survive high concentrations of antibiotics for extended periods of time, is an important contributing factor to therapy failure and development of chronic and recurrent infections. Several recent studies have suggested that this persistence is mediated primarily by (p)ppGpp, through its interactions with toxin-antitoxin modules and polyphosphates. In this study, we address whether these key players play a role in mycobacterial persistence against antibiotics. We targeted these specific pathways in Mycobacterium smegmatis by constructing deletion strains of (p)ppGpp synthetase/hydrolase (relA), polyphosphate kinases (ppk1 and ppk2), exopolyphosphatases (ppx1 and ppx2), and the lon protease. None of these mutant strains exhibited altered levels of persisters against isoniazid and ciprofloxacin, when compared with wild-type strain. Even under conditions in which the stringent response usually gets activated, these strains displayed wild-type persister levels. Interestingly, we also found that unlike Escherichia coli, maintaining M. smegmatis in exponential phase by repeated passaging does not eliminate persisters suggesting that at least against the antibiotics tested, stationary-phase dependent persisters (type I) are not the major contributors. Thus, our data demonstrate that multiple mechanisms of antibiotic persistence exist and that these vary widely among different bacterial species. © 2018 IUBMB Life, 70(9):836-844, 2018.
Language
  • English
Open access status
bronze
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https://sonar.ch/global/documents/187667
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