Haripriyan Jayalekshmi, Binu Christy Rose, Menon Nitasha D, Vanuopadath Muralidharan, Hari Malavika B, Namitha N, Binoy Kesiya, Kumar Anil, Nair Bipin G, Nizet Victor, Kumar Geetha B
School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.
Department of Microbiology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.
Sci Rep. 2025 Jan 30;15(1):3738. doi: 10.1038/s41598-025-86515-9.
Pyomelanogenic P. aeruginosa, frequently isolated from patients with urinary tract infections and cystic fibrosis, possesses the ability to withstand oxidative stress, contributing to virulence and resulting in persistent infections. Whole genome sequence analysis of U804, a pyomelanogenic, multidrug-resistant, clinical isolate, demonstrates the mechanism underlying pyomelanin overproduction. Seven essential oils (EOs) were screened for pyomelanin inhibition. Garlic, cinnamon and thyme EOs were selected for further studies based on their significant anti-virulent properties, like inhibition of pyomelanin production and biofilm formation. Additionally, downregulation of the expression of virulence genes regulated by quorum sensing (QS) and a decrease in levels of the QS signaling molecule, C12-HSL, were also observed. The EO treatment inhibited the survival of U804 in human blood and increased survival of C. elegans, a whole animal model of pathogenesis. EO treatment also resulted in a significant reduction of efflux pump activity, indicative of their effect on antibiotic sensitization. Garlic oil enhanced the permeability of the bacterial membrane, resulting in decreased survival, when combined with sub-MIC concentrations of colistin. This study demonstrates that thyme, cinnamon and garlic EOs can attenuate pyomelanogenic P. aeruginosa virulence traits. Additionally, garlic potentiates drug sensitivity, suggesting its promising therapeutic use in combating pyomelanogenic MDR infections.
经常从尿路感染和囊性纤维化患者中分离出的产黑脓性铜绿假单胞菌具有抵抗氧化应激的能力,这有助于其毒力并导致持续性感染。对一株产黑色素、多重耐药的临床分离株U804进行全基因组序列分析,揭示了黑色素过度产生的潜在机制。筛选了七种精油(EOs)对黑色素生成的抑制作用。基于大蒜、肉桂和百里香精油具有显著的抗毒力特性,如抑制黑色素生成和生物膜形成,选择它们进行进一步研究。此外,还观察到群体感应(QS)调节的毒力基因表达下调以及QS信号分子C12-HSL水平降低。精油处理抑制了U804在人血液中的存活,并提高了秀丽隐杆线虫(一种发病机制的整体动物模型)的存活率。精油处理还导致外排泵活性显著降低,表明它们对抗生素敏感性有影响。当与亚抑菌浓度的黏菌素联合使用时,大蒜油增强了细菌膜的通透性,导致存活率降低。这项研究表明,百里香、肉桂和大蒜精油可以减弱产黑脓性铜绿假单胞菌的毒力特征。此外,大蒜增强了药物敏感性,表明其在对抗产黑脓性多重耐药感染方面具有潜在的治疗用途。