Mechanism of Anti-Virulence Compound 187R Inhibiting Pseudomonas Aeruginosa Type III Secretion System

Abstract

Antibiotics have been widely used for treating bacterial infectious diseases. However, the rapidly emerging of antibiotic resistance has dramatically decreased the efficacy of antibiotics and poses a serious worldwide crisis. In addition, the cell components serving as antibiotics’ targets are conserved in many different bacterial species, as a result, antibiotic treatments disrupt the host microbiota and negatively influence the hosts health condition. Therefore, new alternative strategies for fighting infectious diseases without causing antibiotic resistance and disturbing the host microbiota are needed. Type 3 secretion system (T3SS) is a highly conserved virulence factor presents in many different Gram-negative pathogens. It is required for pathogens such as P. aeruginosa, surviving and initiating infection in their hosts. Therefore, targeting the T3SS is a promising alternative strategy for developing new antimicrobial therapies without disrupting the hosts’ microbial community. Here, we identified a potent T3SS inhibitor, designated 187R, which strongly inhibits the expression of P. aeruginosa T3SS. Our data suggests that 187R inhibits T3SS expression through reducing the T3SS master regulator ExsA at the post-translational level. The impact of this anti-virulence compound on the hosts’ microbial community was also tested using Arabidopsis thaliana phyllosphere as a model. We demonstrates that compared to the traditional antibiotics, our T3SS inhibitor 187R can preserve the microbial community better than antibiotics.