Bacterial virulence factors: a target for heterocyclic compounds to combat bacterial resistance

El‐Aleam, Rehab H. Abd; George, Riham F.; Georgey, Hanan H.; Abdel‐Rahman, Hamdy M.

doi:10.1039/d1ra06238g

Cited by 21 publications

(17 citation statements)

References 140 publications

(200 reference statements)

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“…As explained earlier, the LasI protein produces OdDHL, which binds to the LasR transcription regulator and induces downstream gene expression. When OdDHL binds to LasR, a conformational change occurs, and the activated LasR-OdDHL complex binds to las boxes (lux-box-like sequences) [ 76 ]. In the presence of OdDHL, LasR forms a multimer that can attach to the las boxes.…”

Section: Ahl-dependent Transcription Regulator Biomoleculesmentioning

confidence: 99%

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria

et al. 2022

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Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum sensing (QS) to regulate cellular interactions via small chemical signaling molecules which also help with adaptation under undesirable survival conditions. Proteobacteria use acyl-homoserine lactone (AHL) molecules as autoinducers to sense population density and modulate gene expression. The LuxI-type enzymes synthesize AHL molecules, while the LuxR-type proteins (AHL transcriptional regulators) bind to AHLs to regulate QS-dependent gene expression. Diverse AHLs have been identified, and the diversity extends to AHL synthases and AHL receptors. This review comprehensively explains the molecular diversity of AHL signaling components of Pseudomonas aeruginosa, Chromobacterium violaceum, Agrobacterium tumefaciens, and Escherichia coli. The regulatory mechanism of AHL signaling is also highlighted in this review, which adds to the current understanding of AHL signaling in Gram-negative bacteria. We summarize molecular diversity among well-studied QS systems and recent advances in the role of QS proteins in bacterial cellular signaling pathways. This review describes AHL-dependent QS details in bacteria that can be employed to understand their features, improve environmental adaptation, and develop broad biomolecule-based biotechnological applications.

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Section: Ahl-dependent Transcription Regulator Biomoleculesmentioning

confidence: 99%

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria

et al. 2022

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“…The screening criteria for potential inhibitors of PqsR mainly emphasize on the reduction of bacterial virulence rather than direct killing of bacteria (Abd El‐Aleam et al, 2021; Rasko & Sperandio, 2010). The antibacterial activity of the new inhibitors of PqsR was evaluated in terms of the minimum inhibitory concentrations (MICs) using broth microdilution protocols specified in the Clinical and Laboratory Standards Institute (CLSI) recommendations (Ferraro, 2000) against the Ps.…”

Section: Resultsmentioning

confidence: 99%

“…The emerging of drug resistant bacteria is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions (Jernigan et al, 2020). The potential use of anti-virulence therapies to combat bacterial infections has attracted great interests in recent decades, as the approach may potentially diminish the pathogenicity of target germs with little selection pressure and thus possibly limiting the establishment of resistance (Abd El-Aleam et al, 2021). One of these strategies is to disrupt the bacterial pqs quorum sensing system, which governs multiple virulence traits and biofilm formation through the interaction with PqsR, a Lys-R type transcriptional regulator, with its cognate signal molecules HHQ and PQS (Soheili et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Novel quinoline-based derivatives as the PqsR inhibitor against Pseudomonas aeruginosa PAO1

Huang

She

Zhang

et al. 2022

Journal of Applied Microbiology

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Aims The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa. Methods and Results The results showed that compound 1 suppressed the expression of QS‐related genes and showed the best inhibitory activity to the pqs system of wild‐type Ps. aeruginosa PAO1 with an IC50 of 20.22 μmol L−1. The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration‐dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand‐binding domain of the Lys‐R type transcriptional regulator PqsR as a competitive antagonist. Conclusions The quinoline‐based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced. Significance and Impact of Study The study showed that the quinoline‐based derivatives could be used as an anti‐virulence agent for treating Ps. aeruginosa infections.

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“…Interest in antibiotic adjuvants therapy has increasingly attracted attention within contemporary studies due to the emergence of multidrug-resistant organisms [51][52][53]. Perhaps one of the leading causes of this resistance is the low microbial cell membrane permeability to antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Antibiotic—Lysobacter enzymogenes proteases combination as a novel virulence attenuating therapy

Suaifan¹,

Rahman²,

Abu-Odeh³

et al. 2023

PLoS ONE

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Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics (cefixime, levofloxacin and gentamicin) with Lysobacter enzymogenes (L. enzymogenes) bioactive proteases present in the cell- free supernatant (CFS) have been investigated against the Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative Escherichia coli (E. coli O157:H7). Results indicated that L. enzymogenes CFS had maximum proteolytic activity after 11 days of incubation and higher growth inhibitory properties against MSSA and MRSA compared to E. coli (O157:H7). The combination of L. enzymogenes CFS with cefixime, gentamicin and levofloxacin at sub-MIC levels, has potentiated their bacterial inhibition capacity. Interestingly, combining cefixime with L. enzymogenes CFS restored its antibacterial activity against MRSA. The MTT assay revealed that L. enzymogenes CFS has no significant reduction in human normal skin fibroblast (CCD-1064SK) cell viability. In conclusion, L. enzymogenes bioactive proteases are natural potentiators for antimicrobials with different bacterial targets including cefixime, gentamicin and levofloxacin representing the beginning of a modern and efficient era in the battle against multidrug-resistant pathogens.

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Bacterial virulence factors: a target for heterocyclic compounds to combat bacterial resistance

Abstract: This review presents an overview of different heterocyclic compounds that act as anti-virulence agents in order to overcome microbial resistance.

Cited by 21 publications

References 140 publications

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria

Novel quinoline-based derivatives as the PqsR inhibitor against Pseudomonas aeruginosa PAO1

Antibiotic—Lysobacter enzymogenes proteases combination as a novel virulence attenuating therapy

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