DEVELOPMENT OF QUORUM-SENSING PEPTIDIC INHIBITORS AS NOVEL ANTIMICROBIAL AGENTS

Bacteria use cell-cell communication system termed quorum sensing (QS) to coordinate adaptive properties and developmental stages to cell density. QS Systems are implicated in diverse bacterial processes such as virulence, sporulation and biofilm formation. From these reasons these systems are considered important targets for the design of novel antimicrobial agents.

Bacillus cereus (Bc) is a Gram-positive food borne pathogen that may cause foodborne illnesses, forming biofilms and producing heat resistant spores. Bc has been classified as the 2nd agent responsible for collective food-borne infections. However, the therapeutic potential of direct QS systems of the Bc is yet to be investigated.

PlcR is the major transcriptional regulator of genes encoding virulence factors in Bc. PlcR activity is controlled by the signalling peptide PapR, derived from a 48 aa peptide which is secreted, matured as heptapeptide ADLPFEF. Based on biochemical and structural knowledge, we designed and characterized direct QS synthetic peptides derivatives. Our findings reveals a number of modifications that possess an inhibitory effect over the QS system of Bc. These results are the first step for the future development of a new generation of antimicrobials, antibiofilm and anti-sporulating agents with many possible applications in the field of food safety and human health.