2017
DOI: 10.1016/j.tips.2017.01.004
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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 … Show more

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Cited by 98 publications
(93 citation statements)
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References 159 publications
(198 reference statements)
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“…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.…”
Section: Discussionmentioning
confidence: 99%
“…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.…”
Section: Discussionmentioning
confidence: 99%
“…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].…”
Section: Resultsmentioning
confidence: 99%
“…[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.…”
Section: Antivirulenzunclassified
“…[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.…”
Section: Aufsätzeunclassified