Therapeutic potential of otilonium bromide against Vibrio vulnificus

Abstract

New drugs are urgently required for the treatment of infections due to an increasing number of new strains of diseases-causing pathogens and antibiotic-resistant bacteria. A library of drugs approved by Food and Drug Administration was screened for efficacy against Vibrio vulnificus using antimicrobial assays. We found that otilonium bromide showed potent antimicrobial activity against V.vulnificus and had a synergistic effect in combination with antibiotics. Field emission transmission electron microscope images revealed that otilonium bromide caused cell division defects in V.vulnificus. Moreover, it significantly inhibited V.vulnificus swarming motility and adhesion to host cells at concentrations lower than the minimum inhibitory concentration. To investigate its inhibitory action mechanisms, we examined the effect of otilonium bromide on the expression levels of several proteins crucial for V.vulnificus growth, motility, and adhesion. It decreased the protein expression levels of cAMP receptor protein and flagellin B, but not HlyU or OmpU. In addition, otilonium bromide significantly decreased the expression levels of outer membrane protein TolCV1, thus inhibiting RtxA1 toxin secretion and substantially reducing V.vulnificus cytotoxicity to host cells. Collectively, these findings suggest that otilonium bromide may be considered as a promising candidate for treating V.vulnificus infections.