Comprehensive Phenotypic and Genomic Study for Understanding the Variability in Susceptibility of Listeria...

In this study, we investigated the inhibitory activity of six antimicrobial peptides against 40 Listeria monocytogenes isolates from clinical, environmental, or food samples. Antibiotic susceptibility assays revealed high resistance to clindamycin, whereas resistance to ciprofloxacin was less frequent. Additionally, four isolates were resistant to at least one or two antibiotics. Virulome analysis revealed that the prfA-virulence gene cluster, the main pathogenicity determinant marker in Listeria monocytogenes (prfA, plcA, plcB, hly, mpl and actA) was detected in selected strains. The anti-listeria activities of the bacteriocins, bactofencin A (M14L, M18L), nisin Z, pediocin PA-1 (M31L) and plantaricin S, as well as two lipopeptides, brevibacillin and its synthetic analog brevibacillin Thr1 were assessed. These molecules were selected based on their structural diversity and distinct mechanisms of action. All peptides displayed inhibitory activity against all isolates with a minimal inhibitory and bactericidal concentrations ranging between 0.54 µM and 18.20 µM. In general, the antimicrobial activity of these peptides was not associated with the antibiotic resistance profile or the presence/absence of virulence genes. To elucidate the observed variability in susceptibility, a comparative genomic and structural impact analysis were performed. These revealed polymorphisms occurring in several genes associated with stress response, efflux pumps, membrane and protein biosynthesis. These polymorphisms could help to explain the decreased susceptibility profiles of certain isolates. Overall, through their diversity in structure and mechanism of action, these peptides have been shown to be powerful inhibitors of L. monocytogenes and could serve as alternative to conventional antibiotics for the control of this pathogen.