Repurposing promethazine hydrochloride to inhibit biofilm formation against Burkholderia thailandensis.
Med Microbiol Immunol
; 213(1): 16, 2024 Jul 20.
Article
in En
| MEDLINE
| ID: mdl-39033094
ABSTRACT
Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, an intracellular pathogen with a high mortality rate and significant antibiotic resistance. The high mortality rate and resistance to antibiotics have drawn considerable attention from researchers studying melioidosis. This study evaluated the effects of various concentrations (75, 50, and 25 µg/mL) of promethazine hydrochloride (PTZ), a potent antihistamine, on biofilm formation and lipase activity after 24 h of exposure to B. thailandensis E264. A concentration-dependent decrease in both biofilm biomass and lipase activity was observed. RT-PCR analysis revealed that PTZ treatment not only made the biofilm structure loose but also reduced the expression of btaR1, btaR2, btaR3, and scmR. Single gene knockouts of quorum sensing (QS) receptor proteins (∆btaR1, ∆btaR2, and ∆btaR3) were successfully constructed. Deletion of btaR1 affected biofilm formation in B. thailandensis, while deletion of btaR2 and btaR3 led to reduced lipase activity. Molecular docking and biological performance results demonstrated that PTZ inhibits biofilm formation and lipase activity by suppressing the expression of QS-regulated genes. This study found that repositioning PTZ reduced biofilm formation in B. thailandensis E264, suggesting a potential new approach for combating melioidosis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Promethazine
/
Biofilms
/
Burkholderia
/
Drug Repositioning
Limits:
Humans
Language:
En
Journal:
Med Microbiol Immunol
Year:
2024
Type:
Article
Affiliation country:
China