(333f) Detecting and Killing Pathogenic Bacteria With Lactic Acid Bacteria

Over the last several decades Enterococcus has undergone a troublesome transformation from being a harmless, if not helpful, commensal organism to a major public health threat. Vancomycin-resistant Enterococcus (VRE) are now the primary cause of hospital-acquired infections and no longer susceptible to our most potent antibiotics. This problematic emergence of VRE has motivated us to develop a unique cell-based seek-and-destroy system that first detects Enterococci and then targets them for cell lysis and growth inhibition. To do this, we have cloned the regulatory components of the prgX/prgQ operon from Enterococcus into Lactococcus lactis. These promoters are controlled by a cell-cell communication system where transcription is upregulated by cCF10. This peptide pheromone is constitutively produced and secreted by most, if not all, Enterococci and functions as the signal for our system. Upon detection of cCF10, the promoter overexpresses the downstream antimicrobial peptide (AMP) genes that we have selected for Enterococcus lysis and growth arrest. The AMP products Nisin A, Enterocin A and Enterocin P are then secreted by L. lactis to target and kill Enterococcus by membrane disruption.