Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman, Jordan.
Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, Applied Science Private University, Jordan, Amman.
PLoS One. 2023 Mar 9;18(3):e0282705. doi: 10.1371/journal.pone.0282705. eCollection 2023.
Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics (cefixime, levofloxacin and gentamicin) with Lysobacter enzymogenes (L. enzymogenes) bioactive proteases present in the cell- free supernatant (CFS) have been investigated against the Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative Escherichia coli (E. coli O157:H7). Results indicated that L. enzymogenes CFS had maximum proteolytic activity after 11 days of incubation and higher growth inhibitory properties against MSSA and MRSA compared to E. coli (O157:H7). The combination of L. enzymogenes CFS with cefixime, gentamicin and levofloxacin at sub-MIC levels, has potentiated their bacterial inhibition capacity. Interestingly, combining cefixime with L. enzymogenes CFS restored its antibacterial activity against MRSA. The MTT assay revealed that L. enzymogenes CFS has no significant reduction in human normal skin fibroblast (CCD-1064SK) cell viability. In conclusion, L. enzymogenes bioactive proteases are natural potentiators for antimicrobials with different bacterial targets including cefixime, gentamicin and levofloxacin representing the beginning of a modern and efficient era in the battle against multidrug-resistant pathogens.
将抗生素耐药性最小化是设计和开发新的联合疗法的关键策略。在这项研究中，研究了抗生素（头孢克肟、左氧氟沙星和庆大霉素）与细胞外上清液（CFS）中存在的溶杆菌（L. enzymogenes）生物活性蛋白酶的组合对革兰氏阳性耐甲氧西林敏感金黄色葡萄球菌（MSSA）、耐甲氧西林金黄色葡萄球菌（MRSA）和革兰氏阴性大肠杆菌（E. coli O157:H7）的作用。结果表明，L. enzymogenes CFS 在孵育 11 天后具有最大的蛋白水解活性，并且与大肠杆菌（O157:H7）相比，对 MSSA 和 MRSA 具有更高的生长抑制特性。L. enzymogenes CFS 与头孢克肟、庆大霉素和左氧氟沙星在亚 MIC 水平的组合增强了它们的细菌抑制能力。有趣的是，将头孢克肟与 L. enzymogenes CFS 组合使用恢复了其对 MRSA 的抗菌活性。MTT 分析表明，L. enzymogenes CFS 对人正常皮肤成纤维细胞（CCD-1064SK）的细胞活力没有显著降低。总之，L. enzymogenes 生物活性蛋白酶是针对不同细菌靶标的抗菌药物的天然增效剂，包括头孢克肟、庆大霉素和左氧氟沙星，代表着对抗多药耐药病原体的现代和高效时代的开始。
