Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• highlights the published drug discovery efforts providing insights into the compound binding modes if available. Furthermore, suitability of the individual targets for pathoblocker design is discussed. Keywords: anti-infectives; pathoblockers; PQS; Pseudomonas aeruginosa; quorum sensing; Introduction In

• the pqs system and 2-(2-hydroxyphenyl)thiazole-4-carbaldehyde used by the iqs system (Figure 1). Strategies addressing las and rhl have been reviewed elsewhere [5][11], while to date one study on iqs inhibition has been reported [23]. Many drug discovery efforts towards effective pathoblockers have

• compounds also showed activity against RNA polymerase, a popular target for the development of new antibiotics [52][53]. Hitting such a target would jeopardise the principle of pathoblockers, which should only disarm the bacteria and not kill them. Hence, a follow-up study on PqsD/RNAP selectivity was

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• . Keywords: antimicrobial resistance; bacterial adhesins; bacterial toxins; pathoblockers; quorum sensing; Review 1. Antimicrobial resistance crisis for bacterial infections The current crisis caused by antimicrobial resistance [1][2] demands new strategies to fight infections. Antibiotics have served as

• treatments are urgently needed. 2. Concept of antivirulence drugs or pathoblockers Bacterial virulence is the prime determinant for the deterioration of an infected patient’s health. Blocking bacterial virulence, or pathogenicity, is a new approach that has emerged over the last decade [7][8][9]. The

• inhibition of this adhesion process using glycomimetics as pathoblockers has developed as an area of active research in the last two decades [11][12]. Uropathogenic Escherichia coli (UPEC) is a major cause for chronic and recurrent urinary tract infections. These bacteria employ lectins in order to attach to