New life for an old Drug

The anthelmintic drug niclosamide inhibits pseudomonas aeruginosa quorum sensing

Francesco Imperi, Francesco Massai, Cejoice Ramachandran Pillai, Francesca Longo, Elisabetta Zennaro, Giordano Rampioni, Paolo Visc, Livia Leoni

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

The need for novel antibacterial strategies and the awareness of the importance of quorum sensing (QS) in bacterial infections have stimulated research aimed at identifying QS inhibitors (QSIs). However, clinical application of QSIs identified so far is still distant, likely due to their unsuitability for use in humans. A promising way to overcome this problem is searching for anti-QS side activity among the thousands of drugs approved for clinical use in the treatment of different diseases. Here, we applied this strategy to the search for QSIs, by screening a library of FDA-approved compounds for their ability to inhibit the QS response in the Gram-negative pathogen Pseudomonas aeruginosa. We found that the anthelmintic drug niclosamide strongly inhibits the P. aeruginosa QS response and production of acyl-homoserine lactone QS signal molecules. Microarray analysis showed that niclosamide affects the transcription of about 250 genes, with a high degree of target specificity toward the QS-dependent regulon. Phenotypic assays demonstrated that niclosamide suppresses surface motility and production of the secreted virulence factors elastase, pyocyanin, and rhamnolipids, and it reduces biofilm formation. In accordance with the strong antivirulence activity disclosed in vitro, niclosamide prevented P. aeruginosa pathogenicity in an insect model of acute infection. Besides the finding that an FDA-approved drug has a promising antivirulence activity against one of the most antibiotic-resistant bacterial pathogens, this work provides a proof of concept that a lateral anti-QS activity can be detected among drugs already used in humans, validating a new approach to identify QSIs that could easily move into clinical applications.

Original languageEnglish
Pages (from-to)996-1005
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume57
Issue number2
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Niclosamide
Quorum Sensing
Anthelmintics
Pseudomonas aeruginosa
Pharmaceutical Preparations
Pyocyanine
Acyl-Butyrolactones
Regulon
Pancreatic Elastase
Virulence Factors
Microarray Analysis
Biofilms
Bacterial Infections
Virulence
Insects
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Imperi, F., Massai, F., Pillai, C. R., Longo, F., Zennaro, E., Rampioni, G., ... Leoni, L. (2013). New life for an old Drug: The anthelmintic drug niclosamide inhibits pseudomonas aeruginosa quorum sensing. Antimicrobial Agents and Chemotherapy, 57(2), 996-1005. https://doi.org/10.1128/AAC.01952-12

New life for an old Drug : The anthelmintic drug niclosamide inhibits pseudomonas aeruginosa quorum sensing. / Imperi, Francesco; Massai, Francesco; Pillai, Cejoice Ramachandran; Longo, Francesca; Zennaro, Elisabetta; Rampioni, Giordano; Visc, Paolo; Leoni, Livia.

In: Antimicrobial Agents and Chemotherapy, Vol. 57, No. 2, 02.2013, p. 996-1005.

Research output: Contribution to journalArticle

Imperi, F, Massai, F, Pillai, CR, Longo, F, Zennaro, E, Rampioni, G, Visc, P & Leoni, L 2013, 'New life for an old Drug: The anthelmintic drug niclosamide inhibits pseudomonas aeruginosa quorum sensing', Antimicrobial Agents and Chemotherapy, vol. 57, no. 2, pp. 996-1005. https://doi.org/10.1128/AAC.01952-12
Imperi, Francesco ; Massai, Francesco ; Pillai, Cejoice Ramachandran ; Longo, Francesca ; Zennaro, Elisabetta ; Rampioni, Giordano ; Visc, Paolo ; Leoni, Livia. / New life for an old Drug : The anthelmintic drug niclosamide inhibits pseudomonas aeruginosa quorum sensing. In: Antimicrobial Agents and Chemotherapy. 2013 ; Vol. 57, No. 2. pp. 996-1005.
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