Small Molecules That Sabotage Bacterial Virulence

Abstract

The continued rise of antibiotic resistant bacterial infections has motivated alternative strategies for target discovery and treatment of infections. Antivirulence therapies function through inhibition of in vivo required virulence factors to disarm the pathogen rather than directly target viability or growth. This approach to treating bacterial-mediated diseases may have advantages over traditional antibiotics as it targets factors specific for pathogenesis, potentially reducing selection for resistance and limiting collateral damage to the resident microbiota. This review examines vulnerable molecular mechanisms used by bacteria to cause disease and the antivirulence compounds that sabotage these virulence pathways. By expanding the study of antimicrobial targets beyond those that are essential for growth, antivirulence strategies offer new, innovative opportunities to combat infectious diseases.

Targeting Mycobacterium tuberculosis Sensitivity to Thiol Stress at Acidic pH Kills the Bacterium and Potentiates Antibiotics

“…Mechanism of action studies support that that AC2P36 depletes intracellular thiol pools and this activity is associated with the observed bactericidal activity against Mtb. As pH-dependent adaptations are associated with Mtb virulence and host adaptation, depletion of thiol pools by AC2P36 could be considered an antivirulence strategy to control Mtb infection (Johnson and Abramovitch, 2017). Notably, Mtb exhibits reduced thiol pools, ROS accumulation and associated changes in gene expression at both acidic and neutral pH, supporting that AC2P36 is modulating Mtb physiology independent of pH.…”

How can Naturally Occurring Fatty Acids Neutralize Listeria ?

“…Structural and functional studies on the inhibitory action of such FFAs on virulence will serve as inspiration for the future development of more efficient antivirulence agents. Most importantly, compounds acting by targeting virulence mechanisms represent a promising alternative to traditional antibiotics [8,9]. In contrast to antibiotics, agents acting by an antivirulence mechanism could reduce the pressure for the development of resistance by simply disarming the bacteria of its virulence factors while not preventing bacterial growth [8,9].…”

Über bisherige Denkweisen hinaus – neue Wirkstoffe zur Überwindung der Antibiotika‐Krise

“…[184] Daher führt das Ausschalten dieser Virulenzfaktoren zu einer Entwaffnung der pathogenen Bakterien, verringert so die Infektionsrate und macht die Erreger anfällig fürd ie Abtçtung durch das Immunsystem. [184] Daher führt das Ausschalten dieser Virulenzfaktoren zu einer Entwaffnung der pathogenen Bakterien, verringert so die Infektionsrate und macht die Erreger anfällig fürd ie Abtçtung durch das Immunsystem.…”

“…[121,184,[187][188][189][190] Eine große Anzahl an niedermolekularen Verbindungen wurde in Bezug auf ihre Fähigkeit hin untersucht, in die Regulationspfade und Sekretionssysteme einzugreifen.…”