AimsTo evaluate the antibacterial efficacy of novel antimicrobial peptides (AMPs) against multidrug-resistant (MDR) Salmonella enterica serovar Choleraesuis (Salm.Choleraesuis) and to delineate the AMP-responsive mechanisms of wild-type (WT) and MDR strains. Methods and ResultsProteomic approaches were performed based on two-dimensional gel electrophoresis and liquid chromatography-electrospray ionization-quadrupole- time-of-flight tandem mass spectrometry to analyse the protein profiles of these two strains upon exposure to AMP GW-Q6. Quantitative real-time PCR was conducted to determine the mRNA expression level of the target genes. Furthermore, lipopolysaccharide (LPS) competition analysis was used to verify whether LPS may serve as the potential binding target when AMP approach and adhere to the bacterial surface. ConclusionsThe minimal inhibitory concentration assay revealed that our AMPs were even more effective against the MDR strains (4-32gml(-1)), compared with those for the WT (8-64gml(-1)). LPS dose-dependently suppressed the GW-Q6 antimicrobial activity. Clusters of orthologous groups analysis showed that the majority of the AMP-responsive proteins were involved in cell envelope biogenesis and outer membrane, translation and chaperones. Significance and Impact of the StudyThese results indicated that the novel AMP GW-Q6 serves as a potential candidate for antimicrobial drug development against MDR strains. These findings will also be helpful for expanding our knowledge on the molecular mechanisms of AMP-microbe interaction and the pathogenicity of salmonellosis caused by MDR strains of Salm.Choleraesuis.