Albofungin is a promising broad-spectrum antimicrobial compound against multidrug-resistant bacteria. In the present study, we further investigated
albofungin's biofilm eradication activity and its potential mode of action against
drug-resistant Vibrio parahaemolyticus. Among all derivatives,
albofungin exhibited the best antibiofilm and antibacterial activity with rapid killing effects at 0.12 µg mL-1. Confocal microscopy observation exhibited that
albofungin disrupted V. parahaemolyticus biofilms by killing or dispersing biofilm cells. Meanwhile, scanning electron microscope and fluorescent staining experiments demonstrated that
albofungin rapidly destroyed the integrity and permeability of the bacterial cell membrane. Moreover, this study revealed an antibiofilm mechanism of
albofungin involving inhibition of
peptidoglycan biosynthesis, flagella assembly pathways, and secretion system
proteins in V. parahaemolyticus by quantitative proteomics and validation experiments. Our results highlighted
albofungin's mechanism of action in planktonic cells and biofilms and suggested further development and potential applications of
albofungin for treating
infections caused by
penicillins-and-
cephalosporins-resistant V. parahaemolyticus. IMPORTANCE
Infections caused by multidrug-resistant bacteria, as well as a scarcity of new
antibiotics, have become a major health threat worldwide. To tackle the demand for new and effective treatments, we investigated the mechanism of action of
albofungin, a
natural product derived from Streptomyces, which exhibits potent antimicrobial activity against multidrug-resistant bacteria.
Albofungin showed potent biofilm eradication activity against
penicillins-and-
cephalosporins-resistant Vibrio parahaemolyticus, which expresses a novel metallo-β-lactamase and, thus, reduces their sensitivity to various
antibiotics. We observed membrane disruption and permeation mechanisms in planktonic cells and biofilms after
albofungin treatment, while
albofungin had a weak interaction with
bacterial DNA. Moreover, the antibiofilm mechanism of
albofungin included inhibition of
peptidoglycan biosynthesis, flagellar assembly pathways, and secretion system
proteins. Our finding suggested potential applications of
albofungin as an antibacterial and antibiofilm therapeutic agent.