This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abranches, J. Articles by Lemos, J. A. Search for Related Content PubMed PubMed Citation Articles by Abranches, J. Articles by Lemos, J. A.

 Previous Article  |  Next Article 

Journal of Bacteriology, April 2009, p. 2248-2256, Vol. 191, No. 7
0021-9193/09/$08.00+0     doi:10.1128/JB.01726-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Molecular Alarmone (p)ppGpp Mediates Stress Responses, Vancomycin Tolerance, and Virulence in Enterococcus faecalis

Jacqueline Abranches,^1,2 Alaina R. Martinez,¹ Jessica K. Kajfasz,¹ Violeta Chávez,³ Danielle A. Garsin,³ and José A. Lemos^1,2*

Center for Oral Biology,¹ Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642,² Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, Houston, Texas 77030³

Received 9 December 2008/ Accepted 15 January 2009

The stringent response is a global bacterial response to stress that is mediated by accumulation of the alarmone (p)ppGpp. In this study, treatment with mupirocin was shown to induce high levels of (p)ppGpp production in Enterococcus faecalis, indicating that this nosocomial pathogen can mount a classic stringent response. In addition, (p)ppGpp was found to accumulate in cells subjected to heat shock, alkaline shock, and inhibitory concentrations of vancomycin. Sequence analysis of the E. faecalis genome indicated that (p)ppGpp synthesis is catalyzed by the bifunctional synthetase/hydrolase RelA and the RelQ small synthase. The (p)ppGpp profiles of relA, relQ, and relAQ strains revealed that RelA is the major enzyme responsible for the accumulation of (p)ppGpp during antibiotic or physical stresses, while RelQ appears to be responsible for maintaining basal levels of alarmone during homeostatic growth. Compared to its parent, the relA strain was more susceptible to several stress conditions, whereas complete elimination of (p)ppGpp in a relAQ double mutant restored many of the stress-sensitive phenotypes of relA. Interestingly, growth curves and time-kill studies indicated that tolerance to vancomycin is enhanced in the relA strain but diminished in the relQ and relAQ strains. Finally, virulence of the relAQ strain but not of the relA or relQ strain was significantly attenuated in the Caenorhabditis elegans model. Taken together, these results indicate that (p)ppGpp pools modulate environmental stress responses, vancomycin tolerance, and virulence in this important nosocomial pathogen.

---

* Corresponding author. Mailing address: Center for Oral Biology, Box 611, 601 Elmwood Ave., University of Rochester Medical Center, Rochester, NY 14642. Phone: (585) 275-1850. Fax: (585) 276-0190. E-mail: jose_lemos{at}urmc.rochester.edu

Published ahead of print on 23 January 2009.

---

Journal of Bacteriology, April 2009, p. 2248-2256, Vol. 191, No. 7
0021-9193/09/$08.00+0     doi:10.1128/JB.01726-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Yan, X., Zhao, C., Budin-Verneuil, A., Hartke, A., Rince, A., Gilmore, M. S., Auffray, Y., Pichereau, V. (2009). The (p)ppGpp synthetase RelA contributes to stress adaptation and virulence in Enterococcus faecalis V583. Microbiology 155: 3226-3237 [Abstract] [Full Text]