Exploring the Antivirulence Activity of Pulverulentone A, a Phloroglucinol-Derivative from Callistemon citrinus Leaf Extract, against Multi-Drug Resistant Pseudomonas aeruginosa.

Maha M. Ismail,Nesrin M. Fayek,Mariam Hassan,Mona M. Okba,Sawsan S. Moawad,Fatema R. Saber,Rehab M. Ashour

doi:10.3390/antibiotics10080907

Maha M. Ismail, Nesrin M. Fayek + Show 5 more

Open Access

https://doi.org/10.3390/antibiotics10080907

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Journal: Antibiotics	Publication Date: Jul 25, 2021
Citations: 12	License type: CC BY 4.0

Affiliation: Cairo University

Abstract

(1) Background: Bacterial resistance to antibiotics is a global life-threatening issue. Antivirulence therapy is a promising approach to combat bacterial infections as it disarms the bacteria from their virulence factors with reduced selective pressure and a lower chance of resistance. (2) Methods: Callistemon citrinus leaf extract and its major constituent, Pulverulentone A, were tested for their ability to inhibit biofilm, exopolysaccharides, pyocyanin and proteases produced by MDR P. aeruginosa. In addition, a Galleria mellonella larvae model was employed to evaluate the in vivo cytotoxicity of Pulverulentone A and its ability to combat Pseudomonas infection. Docking study was further performed to investigate Pulverulentone A druggability against main quorum sensing (QS) targets expressed by P. aeruginosa; (3) Results: Both C. citrinus extract and the isolated compound could inhibit biofilm formation, extracellular polymeric substances (EPS) and pigment production by the tested isolates. Unexpectedly, no significant inhibition was observed on proteases production. The in silico docking analysis revealed good interactions of Pulverulentone A with all QS targets examined (LasR, MyfR/PqsR, QscR). Pulverulentone A was safe up to 400 µg·mL−1 in Galleria caterpillars. Moreover, pre-treatment of P. aeruginosa with Pulverulentone A slightly enhanced the survival of the infected larvae. (4) Conclusions: The present study proves Pulverulentone A safety with significant in vitro and in silico antivirulence potential against P. aeruginosa.

Highlights

Pseudomonas aeruginosa is considered one of the serious opportunistic bacteria responsible for many life-threatening conditions and hospital-acquired infections globally, including sepsis, urinary tract implant infection and burn and wound infections [1]
Antivirulence therapy involves the attenuation of microbial virulence factors and microbial pathogenicity, enhancing the clearance of the infection by the immune system [26]
The virulence of 10 clinical and environmental isolates of P. aeruginosa was screened by assessing the ability of these isolates to form biofilm and to produce pyocyanin pigment

Summary

Introduction

Pseudomonas aeruginosa is considered one of the serious opportunistic bacteria responsible for many life-threatening conditions and hospital-acquired infections globally, including sepsis, urinary tract implant infection and burn and wound infections [1]. It forms biofilms on both biotic and abiotic surfaces which confer resistance to most of the available antibiotics [2]. P. aeruginosa support its ability to cause diseases and microbial resistance; these include the ability to form biofilm which hinders penetration of antimicrobials, the antioxidant pyocyanin pigment which plays an important role in bacterial iron uptake and metabolism, and controls efflux pump genes and monooxygenase genes. Pyocyanin is one of the most important virulence factors as it is capable of inhibiting cell respiration and ciliary movement, leading to the reduction in mucus secretion during airway infections [5]

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