An oxidation resistant pediocin PA-1 derivative and penocin A display effective anti- activity in a model human gut environment.

Pediocin PA-1 is a class IIa bacteriocin that is particularly effective against the foodborne pathogen . The loss of activity of PA-1 pediocin due to methionine oxidation is one of the challenges that limit the wider application of the bacteriocin. In this study, we heterologously expressed an oxidation resistant form of pediocin PA-1, i.e., pediocin M31L, and compared its activity to that of native pediocin PA-1 and to penocin A, a pediocin-like bacteriocin that displays a narrower antimicrobial spectrum. Minimal inhibitory concentration assays revealed that pediocin M31L was as effective as PA-1 and more effective than synthetic penocin A against with negligible activity against a range of obligate anaerobic commensal gut bacterial species. The anti- activity of these pediocins was also assessed in a simulated human distal colon model assay using the , spiked at 6.5 0.13 Log CFU/mL, as a bioindicator. At 24 h, pediocin M31L and penocin A (2.6 μM) reduced counts to 3.5 0.4 and 3.64 0.62 Log CFU/mL, respectively, whereas counts were considerably higher, i.e. 7.75 0.43 Log CFU/mL, in the non-bacteriocin-containing control. Ultimately, it was established that synthetic penocin A and the stable pediocin M31L derivative, heterologously produced, display effective anti- activity in a human gut environment.