Repurposing <i>α</i>-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria
Antimicrobial resistance is among the world’s most urgent public health problems. Diminishing of the virulence of bacteria is a promising approach to decrease the development of bacterial resistance. Quorum sensing (QS) systems orchestrate the bacterial virulence in inducer–receptors manner. Bacteri...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/11/2/178 |
| _version_ | 1797483424495173632 |
|---|---|
| author | Ahmad J. Almalki Tarek S. Ibrahim Sameh S. Elhady Khaled M. Darwish Wael A. H. Hegazy |
| author_facet | Ahmad J. Almalki Tarek S. Ibrahim Sameh S. Elhady Khaled M. Darwish Wael A. H. Hegazy |
| author_sort | Ahmad J. Almalki |
| collection | DOAJ |
| description | Antimicrobial resistance is among the world’s most urgent public health problems. Diminishing of the virulence of bacteria is a promising approach to decrease the development of bacterial resistance. Quorum sensing (QS) systems orchestrate the bacterial virulence in inducer–receptors manner. Bacteria can spy on the cells of the host by sensing adrenergic hormones and other neurotransmitters, and in turn, these neurotransmitters can induce bacterial pathogenesis. In this direction, <i>α</i>-adrenergic blockers were proposed as an anti-virulence agents through inhibiting the bacterial espionage. The current study aimed to explore the <i>α</i>-blockers’ anti-QS activities. Within comprehensive in silico investigation, the binding affinities of seven <i>α</i>-adrenoreceptor blockers were evaluated towards structurally different QS receptors. From the best docked <i>α</i>-blockers into QS receptors, terazosin was nominated to be subjected for further in vivo and in vitro anti-QS and anti-virulence activities against <i>Chromobacterium violaceum</i> and <i>Pseudomonas aeruginosa</i>. Terazosin showed a significant ability to diminish the QS-controlled pigment production in <i>C. violaceum.</i> Moreover, Terazosin decreased the <i>P. aeruginosa</i> biofilm formation and down-regulated its QS-encoding genes. Terazosin protected mice from the <i>P. aeruginosa</i> pathogenesis. In conclusion, <i>α</i>-adrenergic blockers are proposed as promising anti-virulence agents as they hinder QS receptors and inhibit bacterial espionage. |
| first_indexed | 2024-03-09T22:46:47Z |
| format | Article |
| id | doaj.art-beacb22d2a0d42eaafbac24cd73ce0d0 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T22:46:47Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-beacb22d2a0d42eaafbac24cd73ce0d02023-11-23T18:27:43ZengMDPI AGAntibiotics2079-63822022-01-0111217810.3390/antibiotics11020178Repurposing <i>α</i>-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative BacteriaAhmad J. Almalki0Tarek S. Ibrahim1Sameh S. Elhady2Khaled M. Darwish3Wael A. H. Hegazy4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptAntimicrobial resistance is among the world’s most urgent public health problems. Diminishing of the virulence of bacteria is a promising approach to decrease the development of bacterial resistance. Quorum sensing (QS) systems orchestrate the bacterial virulence in inducer–receptors manner. Bacteria can spy on the cells of the host by sensing adrenergic hormones and other neurotransmitters, and in turn, these neurotransmitters can induce bacterial pathogenesis. In this direction, <i>α</i>-adrenergic blockers were proposed as an anti-virulence agents through inhibiting the bacterial espionage. The current study aimed to explore the <i>α</i>-blockers’ anti-QS activities. Within comprehensive in silico investigation, the binding affinities of seven <i>α</i>-adrenoreceptor blockers were evaluated towards structurally different QS receptors. From the best docked <i>α</i>-blockers into QS receptors, terazosin was nominated to be subjected for further in vivo and in vitro anti-QS and anti-virulence activities against <i>Chromobacterium violaceum</i> and <i>Pseudomonas aeruginosa</i>. Terazosin showed a significant ability to diminish the QS-controlled pigment production in <i>C. violaceum.</i> Moreover, Terazosin decreased the <i>P. aeruginosa</i> biofilm formation and down-regulated its QS-encoding genes. Terazosin protected mice from the <i>P. aeruginosa</i> pathogenesis. In conclusion, <i>α</i>-adrenergic blockers are proposed as promising anti-virulence agents as they hinder QS receptors and inhibit bacterial espionage.https://www.mdpi.com/2079-6382/11/2/178bacterial virulencequorum sensing<i>α</i>-adrenoreceptor blockers<i>Pseudomonas aeruginosa</i>terazosin |
| spellingShingle | Ahmad J. Almalki Tarek S. Ibrahim Sameh S. Elhady Khaled M. Darwish Wael A. H. Hegazy Repurposing <i>α</i>-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria Antibiotics bacterial virulence quorum sensing <i>α</i>-adrenoreceptor blockers <i>Pseudomonas aeruginosa</i> terazosin |
| title | Repurposing <i>α</i>-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria |
| title_full | Repurposing <i>α</i>-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria |
| title_fullStr | Repurposing <i>α</i>-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria |
| title_full_unstemmed | Repurposing <i>α</i>-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria |
| title_short | Repurposing <i>α</i>-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria |
| title_sort | repurposing i α i adrenoreceptor blockers as promising anti virulence agents in gram negative bacteria |
| topic | bacterial virulence quorum sensing <i>α</i>-adrenoreceptor blockers <i>Pseudomonas aeruginosa</i> terazosin |
| url | https://www.mdpi.com/2079-6382/11/2/178 |
| work_keys_str_mv | AT ahmadjalmalki repurposingiaiadrenoreceptorblockersaspromisingantivirulenceagentsingramnegativebacteria AT tareksibrahim repurposingiaiadrenoreceptorblockersaspromisingantivirulenceagentsingramnegativebacteria AT samehselhady repurposingiaiadrenoreceptorblockersaspromisingantivirulenceagentsingramnegativebacteria AT khaledmdarwish repurposingiaiadrenoreceptorblockersaspromisingantivirulenceagentsingramnegativebacteria AT waelahhegazy repurposingiaiadrenoreceptorblockersaspromisingantivirulenceagentsingramnegativebacteria |