Repurposing phytochemicals as anti‐virulent agents to attenuate quorum sensing‐regulated virulence factors and biofilm formation in Pseudomonas aeruginosa

Abstract

Summary Unregulated consumption and overexploitation of antibiotics have paved the way for emergence of antibiotic‐resistant strains and ‘superbugs’. Pseudomonas aeruginosa is among the opportunistic nosocomial pathogens causing devastating infections in clinical set‐ups globally. Its artillery equipped with diversified virulence elements, extensive antibiotic resistance and biofilms has made it a ‘hard‐to‐treat’ pathogen. The pathogenicity of P. aeruginosa is modulated by an intricate cell density‐dependent mechanism called quorum sensing (QS). The virulence artillery of P. aeruginosa is firmly controlled by QS genes, and their expression drives the aggressiveness of the infection. Attempts to identify and develop novel antimicrobials have seen a sharp rise in the past decade. Among different proposed mechanisms, a novel anti‐virulence approach to target pseudomonal infections by virtue of anti‐QS and anti‐biofilm drugs appears to occupy the centre stage. In this respect, bioactive phytochemicals have gained prominence among the scientific community owing to their significant quorum quenching (QQ) properties. Recent studies have shed light on the QQ activities of various phytochemicals and other drugs in perturbing the QS‐dependent virulence in P. aeruginosa. This review highlights the recent evidences that reinforce the application of plant bioactives for combating pseudomonal infections, their advantages and shortcomings in anti‐virulence therapy.

Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection

“…The last decade has seen an unprecedented increase in AMR globally, underscoring the need for developing alternative intervention strategies to existing antimicrobial regimens ( Khullar et al., 2022 ). In this direction, targeting the bacterial QS systems to attenuate pathogen virulence has gained momentum amongst scientists, paving the way for innovating novel anti-virulence therapies ( Chadha et al., 2021a ). Natural phytoproducts like EOs and their bioactive constituents have exhibited promising anti-QS activities, thereby attenuating the virulence of P. aeruginosa ( Chadha et al., 2021a ).…”

“…In this direction, targeting the bacterial QS systems to attenuate pathogen virulence has gained momentum amongst scientists, paving the way for innovating novel anti-virulence therapies ( Chadha et al., 2021a ). Natural phytoproducts like EOs and their bioactive constituents have exhibited promising anti-QS activities, thereby attenuating the virulence of P. aeruginosa ( Chadha et al., 2021a ). Niu et al pioneered studies on CiNN and demonstrated its ability to interfere with QS in Vibrio harveyi by modulating the transcription of QS genes ( Niu et al., 2006 ).…”

“…Although numerous investigations have identified novel QQ compounds, secondary plant metabolites and bioactive phytochemicals have recently gained attention from the scientific community owing to their anti-QS and anti-biofilm prospects ( Chadha et al., 2021a ). Their antimicrobial properties have been favored worldwide due to their natural existence, easy and economic availability, formidable pharmacological properties, and negligible cytotoxicity ( Chadha et al., 2021c ).…”

Virtual Screening of Phytochemicals Targeting the Main Protease and Spike Protein of SARS-CoV-2: An In silico Approach

“…Thus, the results obtained in the current study yield promising results in harnessing the ancient Indian knowledge of Ayurveda in treating human ailments, including SARS-CoV-2. Moreover, the rampant use of antibiotics in this COVID-19 era has led to a sudden "antibiotic rush" that can accelerate the pace at which resistance in bacterial pathogens evolves, severely compromises the global commitment to curb antimicrobial resistance and the incidence of secondary prevention infections in COVID-19 patients [52]. Thus, bioactive phytochemicals can prove to be the "wonder drugs" with multifaceted properties in this aspect as well.…”

Exploring the therapeutic potential of staphylococcal phage formulations: Current challenges and applications in phage therapy

“…Notably, the ongoing COVID‐19 pandemic and the emergence of SARS‐CoV‐2 variants (Chadha et al, 2021b) have increased the consumption of antibiotics globally (Adebisi et al, 2021). This sudden “antibiotic rush” has the potential to accelerate the pace at which bacterial resistance evolves and can severely compromise the global commitment to curb AMR (Chadha et al, 2021d). Hence, as an effective alternative to conventional antibiotic treatment, phage therapy can prove to be a “game‐changer” in combating superbugs like S. aureus for the decades to come.…”