Direct correlation between overproduction of guanosine 3',5'-bispyrophosphate (ppGpp) and penicillin tolerance in Escherichia coli - PubMed (original) (raw)

Direct correlation between overproduction of guanosine 3',5'-bispyrophosphate (ppGpp) and penicillin tolerance in Escherichia coli

D G Rodionov et al. J Bacteriol. 1995 Aug.

Abstract

The penicillin tolerance exhibited by amino acid-deprived Escherichia coli has been previously proposed to be a consequence of the stringent response. Evidence indicating that penicillin tolerance is directly attributable to guanosine 3',5'-bispyrophosphate (ppGpp) overproduction and not to some other effect of amino acid deprivation is now presented. Accumulation of ppGpp in the absence of amino acid deprivation was achieved by the controlled overexpression of the cloned relA gene, which encodes ppGpp synthetase I. The overproduction of ppGpp resulted in the inhibition of both peptidoglycan and phospholipid synthesis and in penicillin tolerance. The minimum concentration of ppGpp required to establish these phenomena was determined to be 870 pmol per mg (dry weight) of cells. This represented about 70% of the maximum level of ppGpp accumulated during the stringent response. Penicillin tolerance and the inhibition of peptidoglycan synthesis were both suppressed when ppGpp accumulation was prevented by treatment with chloramphenicol, an inhibitor of ppGpp synthetase I activation. Glycerol-3-phosphate acyltransferase, the product of plsB, was recently identified as the main site of ppGpp inhibition in phospholipid synthesis (R. J. Health, S. Jackowski, and C. O. Rock, J. Biol. Chem. 269:26584-26590, 1994). The overexpression of the cloned plsB gene reversed the penicillin tolerance conferred by ppGpp accumulation. This result supports previous observations indicating that the membrane-associated events in peptidoglycan metabolism were dependent on ongoing phospholipid synthesis. Interestingly, treatment with beta-lactam antibiotics by itself induced ppGpp accumulation, but the maximum levels attained were insufficient to confer penicillin tolerance.

PubMed Disclaimer

Cited by

Bacterial persistence: some new insights into an old phenomenon.
Jayaraman R. Jayaraman R. J Biosci. 2008 Dec;33(5):795-805. doi: 10.1007/s12038-008-0099-3. J Biosci. 2008. PMID: 19179767 Review.
Functional characterization of exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GPPA) of Campylobacter jejuni.
Malde A, Gangaiah D, Chandrashekhar K, Pina-Mimbela R, Torrelles JB, Rajashekara G. Malde A, et al. Virulence. 2014 May 15;5(4):521-33. doi: 10.4161/viru.28311. Epub 2014 Feb 25. Virulence. 2014. PMID: 24569519 Free PMC article.
Basal levels of (p)ppGpp in Enterococcus faecalis: the magic beyond the stringent response.
Gaca AO, Kajfasz JK, Miller JH, Liu K, Wang JD, Abranches J, Lemos JA. Gaca AO, et al. mBio. 2013 Sep 24;4(5):e00646-13. doi: 10.1128/mBio.00646-13. mBio. 2013. PMID: 24065631 Free PMC article.
Role of precursor translocation in coordination of murein and phospholipid synthesis in Escherichia coli.
Ehlert K, Höltje JV. Ehlert K, et al. J Bacteriol. 1996 Dec;178(23):6766-71. doi: 10.1128/jb.178.23.6766-6771.1996. J Bacteriol. 1996. PMID: 8955294 Free PMC article.
"It Takes a Village": Mechanisms Underlying Antimicrobial Recalcitrance of Polymicrobial Biofilms.
Orazi G, O'Toole GA. Orazi G, et al. J Bacteriol. 2019 Dec 6;202(1):e00530-19. doi: 10.1128/JB.00530-19. Print 2019 Dec 6. J Bacteriol. 2019. PMID: 31548277 Free PMC article. Review.

References

1. J Bacteriol. 1994 Feb;176(4):966-72 - PubMed
1. Can J Biochem Physiol. 1959 Aug;37(8):911-7 - PubMed
1. Mol Microbiol. 1994 Sep;13(5):911-7 - PubMed
1. J Bacteriol. 1995 Feb;177(4):992-7 - PubMed
1. Biochem Biophys Res Commun. 1968 Oct 10;33(1):108-12 - PubMed

Direct correlation between overproduction of guanosine 3',5'-bispyrophosphate (ppGpp) and penicillin tolerance in Escherichia coli - PubMed (original) (raw)