Sun Ning, Zhi Ziling, Xiao Ting, Deng Xin, He Tenghui, Dong Wanyang, Feng Shuyi, Chen Sisi, Wong Wing-Leung, Yuan Wenchang
Guangzhou 11th People's Hospital, Guangzhou Cadre and Talent Health Management Center, Guangzhou, China.
Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, King Med School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China.
Front Microbiol. 2024 Jul 22;15:1361508. doi: 10.3389/fmicb.2024.1361508. eCollection 2024.
Multidrug resistant bacteria have been a global health threat currently and frontline clinical treatments for these infections are very limited. To develop potent antibacterial agents with new bactericidal mechanisms is thus needed urgently to address this critical antibiotic resistance challenge. Natural products are a treasure of small molecules with high bioactive and low toxicity. In the present study, we demonstrated that a natural compound, honokiol, showed potent antibacterial activity against a number of Gram-positive bacteria including MRSA and VRE. Moreover, honokiol in combination with clinically used β-lactam antibiotics exhibits strong synergistic antimicrobial effects against drug-resistant strains. Biochemical studies further reveal that honokiol may disrupt the GTPase activity, FtsZ polymerization, cell division. These biological impacts induced by honokiol may ultimately cause bacterial cell death. The antibacterial activity of honokiol against infection was also verified with a biological model of larvae. The results support that honokiol is low toxic against the larvae and effectively increases the survival rate of the larvae infected with . These findings demonstrate the potential of honokiol for further structural advancement as a new class of antibacterial agents with high potency against multidrug-resistant bacteria.
多重耐药菌目前已成为全球健康威胁，针对这些感染的一线临床治疗方法非常有限。因此，迫切需要开发具有新杀菌机制的强效抗菌剂，以应对这一严峻的抗生素耐药性挑战。天然产物是具有高生物活性和低毒性的小分子宝库。在本研究中，我们证明了一种天然化合物厚朴酚对包括耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素肠球菌（VRE）在内的多种革兰氏阳性菌具有强效抗菌活性。此外，厚朴酚与临床使用的β-内酰胺类抗生素联合使用时，对耐药菌株表现出强大的协同抗菌作用。生化研究进一步表明，厚朴酚可能会破坏GTP酶活性、FtsZ聚合和细胞分裂。厚朴酚诱导的这些生物学影响最终可能导致细菌细胞死亡。厚朴酚对感染的抗菌活性也通过幼虫生物学模型得到了验证。结果表明，厚朴酚对幼虫毒性低，并有效提高了感染幼虫的存活率。这些发现证明了厚朴酚作为一类对多重耐药菌具有高效力的新型抗菌剂，在进一步结构优化方面的潜力。
