Combined transcriptomic and proteomic analysis of the antibacterial mechanisms of an antimicrobial substance produced by Lactobacillus paracasei FX-6 against colistin-resistant Escherichia coli

Abstract

The emergence and spread of plasmid-mediated mobile colistin resistance in food-borne pathogens threatens food safety and human health, necessitating the development of novel antimicrobial agents. Our previous studies indicate that an antimicrobial substance (AMS) produced by Lactobacillus paracasei FX-6 could be a promising candidate due to its broad-spectrum antimicrobial activities. This study aimed to investigate the antibacterial effects and mechanisms of AMS against colistin-resistant Escherichia coli SHP45. Our results showed that the minimum inhibitory concentration (MIC) of AMS against E. coli SHP45 was 4.0 mg/mL. Flow cytometry showed that AMS disrupts the structural integrity of the cell membrane. According to transmission electron microscope (TEM) observations, the bacterial morphology was severely damaged, and hollow areas formed in the cytoplasm. Further transcriptomic and proteomic analysis revealed that AMS inhibits E. coli SHP45 by co-upregulating critical genes and proteins involved in membrane damage (FtsH, ClpX) and protein hydrolysis (Lon, DnaJ, GroEL), causing DNA damage and metabolic disorders, as well as by inhibiting nutrient transport and energy metabolism. Our results provide new insights into the antibacterial effects of AMS against E. coli SHP45 and suggest that AMS derived from Lactobacillus paracasei FX-6 may be a promising antimicrobial agent for controlling colistin-resistant pathogens in food.