Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Health Sciences, Hainan University, Haikou, 570228, China.
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China.
Med Microbiol Immunol. 2024 Jul 20;213(1):16. doi: 10.1007/s00430-024-00799-8.
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.
类鼻疽病是由伯克霍尔德菌引起的严重传染病，这是一种胞内病原体，具有较高的死亡率和显著的抗生素耐药性。高死亡率和抗生素耐药性引起了研究类鼻疽病的研究人员的极大关注。本研究评估了不同浓度（75、50 和 25µg/mL）的盐酸苯海拉明（PTZ）对泰国伯克霍尔德菌 E264 暴露 24 小时后生物膜形成和脂肪酶活性的影响。观察到生物膜生物量和脂肪酶活性呈浓度依赖性下降。RT-PCR 分析表明，PTZ 处理不仅使生物膜结构松散，还降低了 btaR1、btaR2、btaR3 和 scmR 的表达。成功构建了单基因敲除（QS）受体蛋白（∆btaR1、∆btaR2 和 ∆btaR3）的单基因敲除体。QS 受体蛋白 btaR1 的缺失影响了泰国伯克霍尔德菌的生物膜形成，而 btaR2 和 btaR3 的缺失导致脂肪酶活性降低。分子对接和生物性能结果表明，PTZ 通过抑制 QS 调控基因的表达来抑制生物膜形成和脂肪酶活性。本研究发现，重新定位 PTZ 可减少泰国伯克霍尔德菌 E264 的生物膜形成，为防治类鼻疽病提供了一种新的潜在方法。
