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坎地沙坦酯对……的抗菌活性及作用机制

Antibacterial Activity and Mechanism of Candesartan Cilexetil against .

作者信息

Chen Chengchun, Li Duoyun, Shang Yongpeng, Lin Zhiwei, Wen Zewen, Li Peiyu, Yu Zhijian, Chen Zhong, Liu Xiaoju

机构信息

Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, Huazhong University of Science and Technology Union Shenzhen Hospital, No. 89 Taoyuan Road, Nanshan District, Shenzhen 518052, China.

出版信息

ACS Omega. 2024 May 3;9(19):21510-21519. doi: 10.1021/acsomega.4c02153. eCollection 2024 May 14.

DOI:10.1021/acsomega.4c02153
PMID:38764675
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11097336/
Abstract

infections pose a significant clinical challenge due to their multidrug resistance and propensity for biofilm formation. Exploring alternative treatment options, such as repurposing existing drugs, is crucial in addressing this issue. This study investigates the antibacterial activity of candesartan cilexetil against and elucidates its mechanism of action. Candesartan cilexetil exhibited notable antibacterial activity against both and , with minimum inhibitory concentration (MIC) of ≤25 μM. Time-kill curves demonstrated concentration-dependent bactericidal effects. Candesartan cilexetil could significantly inhibited biofilm formation at the concentration of 1/4× MIC and induced alterations in biofilm structure. Permeability assays revealed compromised bacterial membranes, accompanied by the dissipation of membrane potential in cells after treatment with candesartan cilexetil. Checkerboard analysis showed that bacterial membrane phospholipids phosphatidylglycerol and cardiolipin could neutralize the antibacterial activity of candesartan cilexetil in a dose-dependent manner. Biolayer interferometry (BLI) assay indicated specific interactions between candesartan cilexetil and phosphatidylglycerol or cardiolipin. This study demonstrates the promising antibacterial and antibiofilm activities of candesartan cilexetil against multidrug-resistant . The mechanism of action involves disruption of bacterial membranes, possibly by interacting with membrane phospholipids. These findings underscore the potential utility of candesartan cilexetil as an effective therapeutic agent for combating infections, offering a valuable strategy in the battle against antibiotic-resistant pathogens.

摘要

由于其多重耐药性和形成生物膜的倾向，感染带来了重大的临床挑战。探索替代治疗方案，如重新利用现有药物，对于解决这一问题至关重要。本研究调查了坎地沙坦酯对[具体细菌名称未给出]的抗菌活性，并阐明了其作用机制。坎地沙坦酯对[具体细菌名称未给出]均表现出显著的抗菌活性，最低抑菌浓度（MIC）≤25μM。时间杀菌曲线显示出浓度依赖性杀菌作用。坎地沙坦酯在1/4×MIC浓度时可显著抑制生物膜形成，并诱导生物膜结构改变。通透性测定显示细菌膜受损，在用坎地沙坦酯处理后，[具体细菌名称未给出]细胞的膜电位消散。棋盘分析表明，细菌膜磷脂磷脂酰甘油和心磷脂可呈剂量依赖性中和坎地沙坦酯的抗菌活性。生物层干涉术（BLI）测定表明坎地沙坦酯与磷脂酰甘油或心磷脂之间存在特异性相互作用。本研究证明了坎地沙坦酯对多重耐药[具体细菌名称未给出]具有有前景的抗菌和抗生物膜活性。其作用机制涉及破坏细菌膜，可能是通过与膜磷脂相互作用。这些发现强调了坎地沙坦酯作为对抗[具体细菌名称未给出]感染的有效治疗剂的潜在效用，为对抗抗生素耐药病原体提供了有价值的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/cf690bbfe496/ao4c02153_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/43dbfa8c5042/ao4c02153_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/2adf560b37f4/ao4c02153_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/58b9fd29c76c/ao4c02153_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/0ee8eddc7740/ao4c02153_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/cf690bbfe496/ao4c02153_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/43dbfa8c5042/ao4c02153_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/2adf560b37f4/ao4c02153_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/58b9fd29c76c/ao4c02153_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/0ee8eddc7740/ao4c02153_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd34/11097336/cf690bbfe496/ao4c02153_0005.jpg

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