Cell Envelope Modifications Generating Resistance to Hop Beta Acids and Collateral Sensitivity to Cationic Antimicrobials in Listeria monocytogenes .

Hop beta acids (HBAs) are characteristic compounds from the hop plant that are of interest for their strong antimicrobial activity. In this work, we report a resistance mechanism against HBA in the foodborne pathogen . Using an evolution experiment, we isolated two HBA-resistant mutants with mutations in the gene, which codes for the Multiple Peptide Resistance Factor, an enzyme that confers resistance to cationic peptides and antibiotics in several Gram-positive bacteria by lysinylating membrane phospholipids. Besides the deletion of , the deletion of , which mediates the alanylation of teichoic acids, resulted in increased HBA resistance, suggesting that resistance may be caused by a reduction in positive charges on the cell surface. Additionally, we found that this resistance is maintained at low pH, indicating that the resistance mechanism is not solely based on electrostatic interactions of HBA with the cell surface. Finally, we showed that the HBA-resistant mutants display collateral sensitivity to the cationic antimicrobials polymyxin B and nisin, which may open perspectives for combining antimicrobials to prevent resistance development.