Jordan University of Science and Technology, Faculty of Medicine, Department of Pharmacology, Irbid, Jordan.
Jordan University of Science and Technology, Faculty of Applied Medical Sciences, Department of Medical Laboratory Sciences, Irbid, Jordan.
J Appl Biomed. 2021 Mar;19(1):14-25. doi: 10.32725/jab.2021.001. Epub 2021 Jan 18.
Infections caused by Methicillin-Resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacter cloacae are considered as major therapeutic challenge due to their multidrug-resistant (MDR) phenotype against conventional antibiotics. WLBU2 is an engineered cationic peptide with potent antimicrobial activity. This in-vitro study aimed to evaluate the effects of WLBU2 against clinical isolates of the aforementioned bacteria and assess whether synergistic effects can be achieved upon combination with conventional antibiotics. The minimum inhibitory concentrations (MICs) of antimicrobial agents against bacterial clinical isolates (n = 30/strain) were determined using the microbroth dilution assay. The minimum bactericidal concentrations (MBCs) of WLBU2 were determined from microbroth dilution (MICs) tests by subculturing to agar plates. MICs of WLBU2 were evaluated in the presence of physiological concentrations of salts including NaCl, CaCl2 and MgCl2. To identify bacterial resistance profile, MRSA were treated with Oxacillin, Erythromycin and Vancomycin, while Ceftazidime, Ceftriaxone, Ciprofloxacin and Imipenem were used against Enterobacter cloacae. Combination treatments of antibiotics and sub-inhibitory concentrations of WLBU2 were conducted when MICs indicated intermediate/resistant susceptibility. The MICs/MBCs of WLBU2 were identical for each respective bacteria with values of 0.78-6.25 μM and 1.5-12.5 μM against MRSA and Enterobacter cloacae, respectively. WLBU2 was found as salt resistant. Combination treatment showed that synergistic and additive effects were achieved in many isolates of MRSA and Enterobacter cloacae. Our data revealed that WLBU2 is a potent peptide with bactericidal activity. In addition, it demonstrated the selective advantage of WLBU2 as a potential therapeutic agent under physiological solutions. Our findings also support the combination of WLBU2 and conventional antibiotics with potential application for treatment of resistant bacteria.
耐甲氧西林金黄色葡萄球菌（MRSA）和产超广谱β-内酰胺酶（ESBL）的阴沟肠杆菌引起的感染被认为是主要的治疗挑战，因为它们对传统抗生素具有多药耐药（MDR）表型。WLBU2 是一种具有强大抗菌活性的工程化阳离子肽。本体外研究旨在评估 WLBU2 对上述细菌临床分离株的作用，并评估其与常规抗生素联合使用是否能产生协同作用。使用微量肉汤稀释法测定抗菌药物对细菌临床分离株（n = 30/株）的最低抑菌浓度（MIC）。通过在琼脂平板上进行传代培养，从微量肉汤稀释（MIC）试验中确定 WLBU2 的最低杀菌浓度（MBC）。评估了 WLBU2 在包括 NaCl、CaCl2 和 MgCl2 在内的生理盐浓度存在下的 MIC。为了确定细菌耐药谱，用苯唑西林、红霉素和万古霉素处理 MRSA，而头孢他啶、头孢曲松、环丙沙星和亚胺培南用于阴沟肠杆菌。当 MIC 指示中间/耐药时，进行抗生素和亚抑制浓度 WLBU2 的联合治疗。WLBU2 的 MIC/MBC 对每种相应的细菌均相同，MRSA 和阴沟肠杆菌的数值分别为 0.78-6.25 μM 和 1.5-12.5 μM。WLBU2 具有耐盐性。联合治疗显示，在许多 MRSA 和阴沟肠杆菌的分离株中，协同和相加作用得到了实现。我们的数据表明，WLBU2 是一种具有杀菌活性的有效肽。此外，它显示了 WLBU2 在生理溶液下作为潜在治疗剂的选择性优势。我们的研究结果还支持 WLBU2 与常规抗生素联合使用，具有治疗耐药菌的潜在应用。
