Drug repositioning: doxazosin attenuates the virulence factors and biofilm formation in Gram-negative bacteria.
Anti-virulence
Bacterial resistance
Doxazosin
Gram-negative bacteria
Quorum sensing
α-adrenoreceptor blocker
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
08
01
2023
accepted:
10
04
2023
revised:
03
04
2023
medline:
15
5
2023
pubmed:
20
4
2023
entrez:
20
04
2023
Statut:
ppublish
Résumé
The resistance development is an increasing global health risk that needs innovative solutions. Repurposing drugs to serve as anti-virulence agents is suggested as an advantageous strategy to diminish bacterial resistance development. Bacterial virulence is controlled by quorum sensing (QS) system that orchestrates the expression of biofilm formation, motility, and virulence factors production as enzymes and virulent pigments. Interfering with QS could lead to bacterial virulence mitigation without affecting bacterial growth that does not result in bacterial resistance development. This study investigated the probable anti-virulence and anti-QS activities of α-adrenoreceptor blocker doxazosin against Proteus mirabilis and Pseudomonas aeruginosa. Besides in silico study, in vitro and in vivo investigations were conducted to assess the doxazosin anti-virulence actions. Doxazosin significantly diminished the biofilm formation and release of QS-controlled Chromobacterium violaceum pigment and virulence factors in P. aeruginosa and P. mirabilis, and downregulated the QS encoding genes in P. aeruginosa. Virtually, doxazosin interfered with QS proteins, and in vivo protected mice against P. mirabilis and P. aeruginosa. The role of the membranal sensors as QseC and PmrA was recognized in enhancing the Gram-negative virulence. Doxazosin downregulated the membranal sensors PmR and QseC encoding genes and could in silico interfere with them. In conclusion, this study preliminary documents the probable anti-QS and anti-virulence activities of doxazosin, which indicate its possible application as an alternative or in addition to antibiotics. However, extended toxicological and pharmacological investigations are essential to approve the feasible clinical application of doxazosin as novel efficient anti-virulence agent. KEY POINTS: • Anti-hypertensive doxazosin acquires anti-quorum sensing activities • Doxazosin diminishes the virulence of Proteus mirabilis and Pseudomonas aeruginosa • Doxazosin could dimmish the bacterial espionage.
Identifiants
pubmed: 37079062
doi: 10.1007/s00253-023-12522-3
pii: 10.1007/s00253-023-12522-3
doi:
Substances chimiques
Virulence Factors
0
Doxazosin
NW1291F1W8
Anti-Bacterial Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3763-3778Subventions
Organisme : King Abdulaziz University
ID : IFPIP:1623-166-1443
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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