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Spores and cells of Bacillus cereus, a food borne pathogen responsible for gastroenteritis, viewed with phase-contrast microscopy. The spores are white. They are produced in mother cells, which are darker in color.  Spore diameter is around 1 µm.. © INRA, GUINEBRETIERE Marie-Hélène

Disrupting cell-cell communication to suppress virulence in the bacterium Bacillus cereus

A major public health goal is to identify new strategies for fighting microbes. In Bacillus cereus, a human pathogen, the expression of virulence genes is synchronised and results from communication among bacteria. In a recent study, INRA researchers and Israeli scientists collaborated to develop synthetic peptides capable of interfering with this process. Published on August 14, 2018, in Chemical Communications, the results of this work should lead to novel methods for countering the virulence of bacterial pathogens.

Updated on 09/26/2018
Published on 08/14/2018

In Gram-positive bacteria, some functions are regulated by cell-cell communication systems, which are called quorum-sensing systems. The bacterial pathogen Bacillus cereus causes food poisoning in humans. It can also lead to hospital-acquired infections in at-risk populations (notably the newborn, elderly, or immunocompromised). In this species, the PlcR-PapR system controls transcription of the main virulence genes. PapR is the signaling peptide, and PlcR is the transcriptional regulator. INRA researchers partnered with scientists at the Hebrew University of Jerusalem to inhibit the PlcR-PapR system because of the key role it plays in B. cereus pathogenicity.

  

Drawing on biochemistry and genetics, the researchers created synthetic peptides that were derived from PapR. They then showed that some of these peptides could inhibit the PlcR-PapR system in B. cereus and, consequently, the production of virulence factors.

The peptides did not affect bacterial growth. However, they did block PlcR activity when they were used early on during development. PapR, the endogenous signaling peptide, cannot counteract the inhibition process. This result indicates that the synthetic peptides can act for an extended period during B. cereus growth.

This is the first time that inhibitors of B. cereus quorum sensing have been identified. The peptides' creation and functionality are a proof of concept and key step in the process of characterising intercellular communication systems in bacteria. For several years, INRA researchers, and their national and international collaborators, have been leading the way in this scientific field. The work described here can inform the development of novel medical treatments, in which quorum quenching is used to reduce or fully suppress the virulence of bacterial pathogens. Such strategies could serve as alternatives to attempts to eliminate bacteria via antibiotics, bactericides, or bacteriostats, whose use selects for microbial resistance.

Cell-cell communication in Bacillus cereus. On the left, the endogenous signaling peptide triggers the production of virulence factors following communication among bacterial cells (quorum sensing). On the right, the synthetic signaling peptide inhibits the production of virulence factors by interfering with communication among bacterial cells (quorum quenching).. © INRA, INRA
Cell-cell communication in Bacillus cereus. On the left, the endogenous signaling peptide triggers the production of virulence factors following communication among bacterial cells (quorum sensing). On the right, the synthetic signaling peptide inhibits the production of virulence factors by interfering with communication among bacterial cells (quorum quenching). © INRA, INRA

Contact(s)
Scientific contact(s):

  • Didier Lereclus (33 1 34 65 21 00) Joint Research Unit for Food and Gut Microbiology for Human Health - MICALIS (INRA, AgroParisTech)
  • Leyla Slamti (33 1 34 65 23 82) Joint Research Unit for Food and Gut Microbiology for Human Health - MICALIS (INRA, AgroParisTech)
  • Zvi Hayouka Institute of Biochemistry, Food Science and Nutrition, Hebrew University of Jerusalem, Israel
Press Relations:
INRA News Office (33 1 42 75 91 86)
Associated Division(s):
Microbiology and the Food Chain
Associated Centre(s):
Jouy-en-Josas

Reference

Avishag Yehuda, Leyla Slamti, Racheli Bochnik-Tamir, Einav Malach, Didier Lereclus and Zvi Hayouka Turning off Bacillus cereus quorum sensing system with peptidic analogs Chemical Communications, 2018 DOI: 10.1039/C8CC05496G