Could the analgesic drugs, paracetamol and indomethacin, function as quorum sensing inhibitors?

Seleem, Noura M.; Atallah, Hamada; Latif, Hemat K. Abd El; Shaldam, Moataz A.; El-Ganiny, Amira M.

doi:10.1016/j.micpath.2021.105097

Cited by 14 publications

(8 citation statements)

References 70 publications

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“…With these conclusive results, our previous findings from the qRT-PCR analysis were successfully translated, thereby asserting that MeT harbors anti-QS and anti-virulence potential against P. aeruginosa. Virulence attenuation as a consequence of QS disruption in P. aeruginosa has been recently documented in several investigations in vitro [25,26]. Similar type of anti-virulence approach has also proven to be successful in protecting Caenorhabditis elegans against pseudomonal infections [27,28].…”

Section: Met Displays Anti-virulence Properties By Phenotypically Inh...mentioning

confidence: 93%

“…Cell adhesion was also notably lowered at 1/8 MIC, which was visualized by the reduction in cell number per microscopic field. Recent studies have also reported the anti-fouling prospects of other repurposed drugs that possess profound anti-QS activity against P. aeruginosa, including paracetamol [26] and ibuprofen [24]. Inhibition of EPS production along with lowered eDNA release and total biofilm protein are also known to augment the anti-virulence potential of phytochemicals in vitro [10,11].…”

Section: Met Inhibits Biofilm Development By Abrogating Eps Productio...mentioning

confidence: 99%

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Anti-virulence prospects of Metformin against Pseudomonas aeruginosa: A new dimension to a multifaceted drug

Chadha

Khullar

Gulati

et al. 2023

Microbial Pathogenesis

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Section: Met Displays Anti-virulence Properties By Phenotypically Inh...mentioning

confidence: 93%

Section: Met Inhibits Biofilm Development By Abrogating Eps Productio...mentioning

confidence: 99%

Anti-virulence prospects of Metformin against Pseudomonas aeruginosa: A new dimension to a multifaceted drug

Chadha

Khullar

Gulati

et al. 2023

Microbial Pathogenesis

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“…Sterile supernatants (100 μL) were added to the wells made in the skim milk agar plates. Clear zones that formed around the wells after 24 h of incubation at 37 °C were measured [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Antibacterial, antibiofilm, and anti-quorum sensing activities of pyocyanin against methicillin-resistant Staphylococcus aureus: in vitro and in vivo study

et al. 2023

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Background Methicillin-resistant Staphylococcus aureus (MRSA) infections are considered a major public health problem, as the treatment options are restricted. Biofilm formation and the quorum sensing (QS) system play a pivotal role in S. aureus pathogenicity. Hence, this study was performed to explore the antibacterial effect of pyocyanin (PCN) on MRSA as well as its effect on MRSA biofilm and QS. Results Data revealed that PCN exhibited strong antibacterial activity against all test MRSA isolates (n = 30) with a MIC value equal to 8 µg/ml. About 88% of MRSA biofilms were eradicated by PCN treatment using the crystal violet assay. The disruption of MRSA biofilm was confirmed using confocal laser scanning microscopy, which showed a reduction in bacterial viability (approximately equal to 82%) and biofilm thickness (approximately equal to 60%). Additionally, the disruption of the formation of microcolonies and the disturbance of the connection between bacterial cells in the MRSA biofilm after PCN treatment were examined by scanning electron microscopy. The 1/2 and 1/4 MICs of PCN exerted promising anti-QS activity without affecting bacterial viability; Agr QS-dependent virulence factors (hemolysin, protease, and motility), and the expression of agrA gene, decreased after PCN treatment. The in silico analysis confirmed the binding of PCN to the AgrA protein active site, which blocked its action. The in vivo study using the rat wound infection model confirmed the ability of PCN to modulate the biofilm and QS of MRSA isolates. Conclusion The extracted PCN seems to be a good candidate for treating MRSA infection through biofilm eradication and Agr QS inhibition.

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“…Also, the potential of ketoprofen and its derivatives in inhibiting QS in P. aeruginosa , as well as their related in‐silico and in‐vitro studies has been investigated (Tajani et al, 2021). The innovative role of tenoxicam (Askoura et al, 2020) and paracetamol (Seleem et al, 2021) as QS‐inhibitor has also been detected.…”

Section: Introductionmentioning

confidence: 99%

Ketoprofen, piroxicam and indomethacin-suppressed quorum sensing and virulence factors in Acinetobacter baumannii

El-Shaer

Shaldam

Shaaban

2022

Journal of Applied Microbiology

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Aim Quorum sensing (QS) inhibition is a promising strategy to suppress bacterial virulence and control infection caused by Gram‐negative and Gram‐positive bacteria. This study explores the QS inhibiting activity of the non‐steroidal anti‐inflammatory drugs (NSAIDs) in Acinetobacter baumannii. Methods and Results Ketoprofen, piroxicam and indomethacin revealed QS inhibition via elimination of violacein production of the reporter strain Chromobacterium violaceum ATCC 12472 without affecting bacterial growth. The minimal inhibitory concentration (MIC) of ketoprofen, piroxicam and indomethacin was determined against A. baumannii strains ATCC 17978, ATCC 19606, A1, A11 and A27 by the microbroth dilution method. The MICs of ketoprofen against tested isolates were 0.7–6.25 mg ml−1, piroxicam MICs were 1.25–2.5 mg ml−1, and indomethacin MICs were 3.12–12.5 mg ml−1. Those compounds significantly inhibited QS‐associated virulence factors such as biofilm formation, and surface motility, as well as, significantly increased bacterial tolerance to oxidative stress without affecting bacterial growth. On the molecular level, the three compounds significantly inhibited the transcription of QS regulatory genes abaI/abaR and biofilm‐regulated genes cusD and pgaB. Molecular docking analysis revealed the potent binding affinity of the three compounds with AbaI via hydrogen and/or hydrophobic bonds. Conclusion These results indicate that NSAIDs, ketoprofen, piroxicam and indomethacin, could be potential inhibitors of the QS and could suppress the QS‐related virulence factors of A. baumannii. Significance and Impact Ketoprofen, piroxicam and indomethacin could provide promising implications and strategies for combating the virulence and pathogenesis of A. baumannii.

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Could the analgesic drugs, paracetamol and indomethacin, function as quorum sensing inhibitors?

Cited by 14 publications

References 70 publications

Anti-virulence prospects of Metformin against Pseudomonas aeruginosa: A new dimension to a multifaceted drug

Anti-virulence prospects of Metformin against Pseudomonas aeruginosa: A new dimension to a multifaceted drug

Antibacterial, antibiofilm, and anti-quorum sensing activities of pyocyanin against methicillin-resistant Staphylococcus aureus: in vitro and in vivo study

Ketoprofen, piroxicam and indomethacin-suppressed quorum sensing and virulence factors in Acinetobacter baumannii

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