Drug repurposing: Antimicrobial and antibiofilm effects of penfluridol against Enterococcus faecalis

Abstract

The bacterium Enterococcus faecalis has increasingly attracted global attention as an important opportunistic pathogen due to its ability to form biofilms that are known to increase drug resistance. However, there are still no effective antibiofilm drugs in clinical settings. Here, by drug repurposing, we investigated the antibacterial activity of penfluridol (PF), an oral long‐acting antipsychotic approved by the FDA, against E. faecalis type strain and its clinical isolates. It was found that PF inhibited the growth of E. faecalis planktonic cells with the MIC and MBC of 7.81 µg/ml and 15.63 ~ 62.50 µg/ml, respectively. Moreover, PF could significantly prevent the biofilm formation of E. faecalis at the concentration of 1 × MIC. Furthermore, PF significantly eradicated 24 h pre‐formed biofilms of E. faecalis in a dose‐dependent manner, with a concentration range of 1 × MIC to 8 × MIC. Here, through the checkerboard method with other tested conventional antibiotics, we also determined that gentamycin, penicillin G, and amikacin showed partial synergistic antibacterial effects with PF. Also, PF showed almost no hemolysis on human erythrocytes. In a mouse peritonitis model, a single dose of 20 mg/kg of PF treatment could significantly reduce the bacterial colonization in the liver (~5‐fold reduction) and spleen (~3‐fold reduction). In conclusion, these findings indicated that after structural optimization, PF has the potential as a new antibacterial agent against E. faecalis.

Discovery of New Fusobacterium nucleatum Inhibitors to Attenuate Migratory Capability of Colon Cancer Cells by the Drug Repositioning Strategy

“…nucleatum. Previously, PF exhibited broad antibactericidal activity against Enterococcus faecalis and Staphylococcus aureus. , Moreover, PF possessed significant biofilm inhibitory potency against E. faecalis and S.…”

Discovery of New Fusobacterium nucleatum Inhibitors to Attenuate Migratory Capability of Colon Cancer Cells by the Drug Repositioning Strategy

“…nucleatum. Previously, PF exhibited broad antibactericidal activity against Enterococcus faecalis and Staphylococcus aureus. , Moreover, PF possessed significant biofilm inhibitory potency against E. faecalis and S.…”

In vitro synergy screens of FDA-approved drugs reveal novel zidovudine- and azithromycin-based combinations with last-line antibiotics against Klebsiella pneumoniae

“…Ibandronate and other bisphosphonate derivatives are anti-parasitic drugs inhibiting the synthesis of essential isoprenoids 48 , 49 . The antipsychotic penfluridol displayed partial synergistic activity with aminoglycosides and β-lactams against Enterococcus faecalis 50 . To the best of our knowledge, here we report for the first time the antibacterial activity of both drugs with tigecycline against enterobacteria; (2) Bleomycin plus colistin or fosfomycin.…”

Anti-infective Efficacy of Duloxetine against Catheter-Associated Urinary Tract Infections Caused by Gram-Positive Bacteria

“…The results revealed that the tested repurposed drugs demonstrated the ability to both reduce and inhibit biofilm formation on matrices and hydroxyapatite after treatment with duloxetine. 38 Various studies reported the antibiofilm potency of repurposed drugs against S. aureus biofilm formation. Later, duloxetine was investigated for its antiadhesive properties against S. aureus using an in vitro bladder model, which was used to study the prevention of biofilm formation on the catheter surface.…”

“…The results revealed that the tested repurposed drugs demonstrated the ability to both reduce and inhibit biofilm formation on matrices and hydroxyapatite after treatment with duloxetine. 38 Various studies reported the antibiofilm potency of repurposed drugs against S. aureus biofilm formation.…”

Discovery of New Fusobacterium nucleatum Inhibitors to Attenuate Migratory Capability of Colon Cancer Cells by the Drug Repositioning Strategy

“…nucleatum. Previously, PF exhibited broad antibactericidal activity against Enterococcus faecalis and Staphylococcus aureus. , Moreover, PF possessed significant biofilm inhibitory potency against E. faecalis and S.…”

In vitro synergy screens of FDA-approved drugs reveal novel zidovudine- and azithromycin-based combinations with last-line antibiotics against Klebsiella pneumoniae

“…Ibandronate and other bisphosphonate derivatives are anti-parasitic drugs inhibiting the synthesis of essential isoprenoids 48 , 49 . The antipsychotic penfluridol displayed partial synergistic activity with aminoglycosides and β-lactams against Enterococcus faecalis 50 . To the best of our knowledge, here we report for the first time the antibacterial activity of both drugs with tigecycline against enterobacteria; (2) Bleomycin plus colistin or fosfomycin.…”

Anti-infective Efficacy of Duloxetine against Catheter-Associated Urinary Tract Infections Caused by Gram-Positive Bacteria

“…The results revealed that the tested repurposed drugs demonstrated the ability to both reduce and inhibit biofilm formation on matrices and hydroxyapatite after treatment with duloxetine. 38 Various studies reported the antibiofilm potency of repurposed drugs against S. aureus biofilm formation. Later, duloxetine was investigated for its antiadhesive properties against S. aureus using an in vitro bladder model, which was used to study the prevention of biofilm formation on the catheter surface.…”

“…The results revealed that the tested repurposed drugs demonstrated the ability to both reduce and inhibit biofilm formation on matrices and hydroxyapatite after treatment with duloxetine. 38 Various studies reported the antibiofilm potency of repurposed drugs against S. aureus biofilm formation.…”

Discovery of New Fusobacterium nucleatum Inhibitors to Attenuate Migratory Capability of Colon Cancer Cells by the Drug Repositioning Strategy

“…nucleatum. Previously, PF exhibited broad antibactericidal activity against Enterococcus faecalis and Staphylococcus aureus. , Moreover, PF possessed significant biofilm inhibitory potency against E. faecalis and S.…”

In vitro synergy screens of FDA-approved drugs reveal novel zidovudine- and azithromycin-based combinations with last-line antibiotics against Klebsiella pneumoniae

“…Ibandronate and other bisphosphonate derivatives are anti-parasitic drugs inhibiting the synthesis of essential isoprenoids 48 , 49 . The antipsychotic penfluridol displayed partial synergistic activity with aminoglycosides and β-lactams against Enterococcus faecalis 50 . To the best of our knowledge, here we report for the first time the antibacterial activity of both drugs with tigecycline against enterobacteria; (2) Bleomycin plus colistin or fosfomycin.…”

Anti-infective Efficacy of Duloxetine against Catheter-Associated Urinary Tract Infections Caused by Gram-Positive Bacteria

“…The results revealed that the tested repurposed drugs demonstrated the ability to both reduce and inhibit biofilm formation on matrices and hydroxyapatite after treatment with duloxetine. 38 Various studies reported the antibiofilm potency of repurposed drugs against S. aureus biofilm formation. Later, duloxetine was investigated for its antiadhesive properties against S. aureus using an in vitro bladder model, which was used to study the prevention of biofilm formation on the catheter surface.…”

“…The results revealed that the tested repurposed drugs demonstrated the ability to both reduce and inhibit biofilm formation on matrices and hydroxyapatite after treatment with duloxetine. 38 Various studies reported the antibiofilm potency of repurposed drugs against S. aureus biofilm formation.…”