Chandar Brinda, Poovitha Sundar, Ilango Kaliappan, MohanKumar Ramasamy, Parani Madasamy
Genomics Laboratory, Department of Genetic Engineering, School of Bioengineering, SRM UniversityKattankulathur, India.
Interdisciplinary Institute of Indian System of Medicine, SRM UniversityKattankulathur, India.
Front Microbiol. 2017 Aug 22;8:1580. doi: 10.3389/fmicb.2017.01580. eCollection 2017.
Improper use of antibiotics has led to a great concern in the development of pathogenic microbial resistance. New Delhi metallo-β-lactamase 1 (NDM-1) producing bacteria are resistant to most of the β-lactam antibiotics, and so far, no new compounds have been clinically tested against these bacteria. In this study, ethanol extracts from the leaves of 240 medicinal plant species were screened for antibacterial activity against an NDM-1 strain. The extracts that showed antibacterial activity were then tested for minimum inhibitory concentrations (MICs) and zones of inhibition. The extract from G. Don, Welw. ex Hiern, L., Willd., L., and L. showed bactericidal activity between 5 and 15 mg/ml and the MIC was between 2.56 and 5.12 mg/ml. All six plant extracts inhibited activity of the NDM-1 enzyme , and the IC50 value ranged between 0.50 and 1.2 ng/μl. Disruption of bacterial cell wall integrity by the plant extracts was clearly visible with scanning electron microscopy. Increases in membrane permeability caused 79.4-89.7% bacterial cell deaths as investigated by fluorescence-activated cell sorting. All the plant extracts showed synergistic effects when combined with colistin [fractional inhibitory concentration (ΣFIC) = 0.125-0.375], meropenem (ΣFIC = 0.09-0.313), and tetracycline (ΣFIC = 0.125-0.313). Thus, the plant extracts can be fractionated for the identification of active compounds, which could be used as new antibacterial compounds for the development of drugs against NDM-1 in addition to their use in combination therapy.
抗生素的不当使用已引起对病原微生物耐药性发展的高度关注。产新德里金属β-内酰胺酶1（NDM-1）的细菌对大多数β-内酰胺类抗生素具有耐药性，迄今为止，尚无针对这些细菌的新化合物进行临床试验。在本研究中，对240种药用植物叶片的乙醇提取物进行了针对NDM-1菌株的抗菌活性筛选。然后对显示出抗菌活性的提取物进行最低抑菌浓度（MIC）和抑菌圈测试。来自G. Don、Welw. ex Hiern、L.、Willd.、L.和L.的提取物在5至15 mg/ml之间显示出杀菌活性，MIC在2.56至5.12 mg/ml之间。所有六种植物提取物均抑制NDM-1酶的活性，IC50值在0.50至1.2 ng/μl之间。用扫描电子显微镜可清楚地看到植物提取物对细菌细胞壁完整性的破坏。通过荧光激活细胞分选研究发现，膜通透性增加导致79.4 - 89.7%的细菌细胞死亡。所有植物提取物与黏菌素[分数抑菌浓度（ΣFIC）= 0.125 - 0.375]、美罗培南（ΣFIC = 0.09 - 0.313）和四环素（ΣFIC = 0.125 - 0.313）联合使用时均显示出协同作用。因此，可对植物提取物进行分离以鉴定活性化合物，这些活性化合物除了用于联合治疗外，还可作为新型抗菌化合物用于开发抗NDM-1的药物。
