SET-M33 peptide as a selective in vitro antimicrobial agent against the porcine respiratory pathogen Glaesserella parasuis

As we face the threat from bacterial pathogens that are resistant to many conventional antibiotics, many current research efforts focus on expanding our arsenal of antimicrobial compounds. However, identifying use cases in which such new antimicrobials can effectively target pathogens while minimizing collateral damage in the commensal microbiota remains a challenge. To tackle this challenge, we focused on one new antimicrobial, the synthetic antimicrobial peptide SET-M33, and examined its ability to target porcine respiratory pathogens and a collection of porcine commensal nasal microbiota members in vitro. Our experiments revealed three key results. First, there were large differences in SET-M33 sensitivity across the tested strains. In particular, pathogenic Glaesserella parasuis was highly sensitive to SET-M33 at concentrations that did not affect the growth of most commensal strains. Second, some of the tested commensal strains (i.e. Rothia nasimurium and Staphylococcus aureus) were able to inactivate SET-M33 during in vitro cultivation. Third, despite this potential for SET-M33 inactivation by commensal strains, SET-M33 was still able to selectively eliminate pathogenic G. parasuis from in vitro co-cultures that also contained R. nasimurium. Overall, this study highlights the substantial complexity that emerges from the interplay between antimicrobials, pathogens, and commensals, even within a comparatively simple in vitro system, and provides a template for identifying suitable use cases for newly developed antimicrobials.