Recent Advances in Anti-virulence Therapeutic Strategies With a Focus on Dismantling Bacterial Membrane Microdomains, Toxin Neutralization, Quorum-Sensing Interference and Biofilm Inhibition

Abstract

Antimicrobial resistance constitutes one of the major challenges facing humanity in the Twenty-First century. The spread of resistant pathogens has been such that the possibility of returning to a pre-antibiotic era is real. In this scenario, innovative therapeutic strategies must be employed to restrict resistance. Among the innovative proposed strategies, anti-virulence therapy has been envisioned as a promising alternative for effective control of the emergence and spread of resistant pathogens. This review presents some of the anti-virulence strategies that are currently being developed, it will cover strategies focused on quench pathogen quorum sensing (QS) systems, disassemble of bacterial functional membrane microdomains (FMMs), disruption of biofilm formation and bacterial toxin neutralization.

Keywords: anti-virulence therapy; antibiotic resistance; bacterial membrane microdomains; bacterial toxins; biofilms; quorum sensing.

Figure 1

Schematic representation of anti-virulence strategies covered in this review. Membrane microdomains: The functional membrane microdomains (FMMs) are targeted by small molecules (statins, zaragozic acid) that inhibit the biosynthesis of their major constituent lipids (hopanoids, carotenoids). Anti-biofilm agents: This strategy focused on the use of agents that block the initial bacterial attachment to surface during biofilm formation and agents that destroy preformed biofilm. Quorum-sensing: The anti-virulence strategy that seeks modulate the production of virulence factors through interference with the quorum-sensing networks. Toxin neutralization: A strategy focused on block the action of toxins on host target cells. HMG-CoA (3-hydroxy-3-methylglutaryl-CoA), MVA (mevalonic acid), MVPP (5-diphosphomevalonate), GAP (D-glyceraldehyde-3-phosphate), HMBPP (4-hydroxy-3-methylbut-2-enyl-diphosphate), IPP (isopentenyl diphosphate), QS (quorum sensing), AMPs (antimicrobial peptides).