Pseudomonas

Pseudomonas is a genus of Gram-negative bacteria belonging to the family Pseudomonadaceae in the class Gammaproteobacteria. The 313 members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a wide range of niches. Their ease of culture in vitro and availability of an increasing number of Pseudomonas strain genome sequences has made the genus an excellent focus for scientific research; the best studied species include P. aeruginosa in its role as an opportunistic human pathogen, the plant pathogen P. syringae, the soil bacterium P. putida, and the plant growth-promoting P. fluorescens, P. lini, P. migulae, and P. graminis. Because of their widespread occurrence in water and plant seeds such as dicots, the pseudomonads were observed early in the history of microbiology. The generic name Pseudomonas created for these organisms was defined in rather vague terms by Walter Migula in 1894 and 1900 as a genus of Gram-negative, rod-shaped, and

Design and Evaluation of New Quinazolin-4(3H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa

Eduard Vico Oton

P. aeruginosa (PA) continues to pose a threat to global public health due to its high levels of antimicrobial resistance (AMR). The ongoing AMR crisis has led to an alarming shortage of effective treatments for resistant microbes, and hence there is a pressing demand for the development of novel antimicrobial interventions. The potential use of antivirulence therapeutics to tackle bacterial infections has attracted considerable attention over the past decades as they hamper the pathogenicity of target microbes with reduced selective pressure, minimizing the emergence of resistance. One such approach is to interfere with the PA pqs quorum sensing system which upon the interaction of PqsR, a Lys-R type transcriptional regulator, with its cognate signal molecules 4-hydroxy-2-heptylquinoline (HHQ) and 2-heptyl-3-hydroxy-4-quinolone (PQS), governs multiple virulence traits and host-microbe interactions. In this study, we report the hit identification and optimization of PqsR antagonists using virtual screening coupled with whole cell assay validation. The optimized hit compound 61 ((R)-2-(4-(3-(6-chloro-4-oxoquinazolin-3(4H)-yl)-2-hydroxypropoxy)phenyl)acetonitrile) was found to inhibit the expression of the PA P-pqsA promoter controlled by PqsR with an IC50 of 1 mu M. Using isothermal titration calorimetry, a K-d of 10 nM for the P-qsR ligand binding domain (PqsR(LBD)) was determined for 61. Furthermore, the crystal structure of 61 with PqsR(LBD) was attained with a resolution of 2.65 angstrom. Compound 61 significantly reduced levels of pyocyanin, PQS, and HHQ in PAO1-L, PA14 lab strains and PAK6085 clinical isolate. Furthermore, this compound potentiated the effect of ciprofloxacin in early stages of biofilm treatment and in Galleria mellonella infected with PA. Altogether, this data shows 61 as a potent PqsR inhibitor with potential for hit to lead optimization toward the identification of a PA QS inhibitor which can be advanced into preclinical development.

AMER CHEMICAL SOC2021

Pseudomonas entomophila: A Versatile Bacterium with Entomopathogenic Properties

Guennaëlle Dieppois, Bruno Lemaitre, Onya Opota

Pseudomonas entomophila is unique among Pseudomonas species in being able to activate a systemic immune response in both Drosophila larvae and adults. It has been subsequently shown that oral infections with high doses of this bacterium are highly pathogenic to Drosophila and cause massive destruction of the Drosophila gut epithelium. Besides Drosophila, P. entomophila was able to kill other insects from at least three different orders, suggesting that it has a potentially wide host range and making it a promising model for the study of host pathogen interactions and for the development of bio-control agents against insect pests. In order to unravel the features contributing to P. entomophila’s pathogenic properties, its complete genome was sequenced and genetic screens were performed to identify virulence factors encoded by this bacterium. The aim of this chapter is to review the current knowledge we have on this bacterium with a particular focus on the pathogenesis it induces, its virulence effectors and their genetic regulation

Springer2014

Design and Evaluation of New Quinazolin-4(3H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa

Eduard Vico Oton

AMER CHEMICAL SOC2021

Design and Evaluation of New Quinazolin-4(3H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa

Physico-chemical aspects of the adhesion and biofilm formation by "Pseudomonas aeruginosa" on unmodified and modified PVC from endotracheal tubes

Pseudomonas entomophila: A Versatile Bacterium with Entomopathogenic Properties

Physico-chemical aspects of the adhesion and biofilm formation by "Pseudomonas aeruginosa" on unmodified and modified PVC from endotracheal tubes

Design and Evaluation of New Quinazolin-4(3H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa

Pseudomonas entomophila: A Versatile Bacterium with Entomopathogenic Properties