J Appl Biomed 19:14-25, 2021 | DOI: 10.32725/jab.2021.001

Synergism between WLBU2 peptide and antibiotics against methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing Enterobacter cloacae

Lina Elsalem1, *, Suhaila Al Sheboul2, Ayat Khasawneh1,3
1 Jordan University of Science and Technology, Faculty of Medicine, Department of Pharmacology, Irbid, Jordan
2 Jordan University of Science and Technology, Faculty of Applied Medical Sciences, Department of Medical Laboratory Sciences, Irbid, Jordan
3 The Jordanian Royal Medical Services, Department of Clinical Pathology and Microbiology, Amman, Jordan

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.

Keywords: Antimicrobial peptide; Combination treatment; Resistant bacteria; Salt sensitivity; Synergism; WLBU2
Grants and funding:

This study was financially supported by the Deanship of Research of Jordan University of Science and Technology [Grant number 20180453].

Conflicts of interest:

The authors declare no conflict or competing of interests.

Received: September 3, 2020; Revised: October 31, 2020; Accepted: January 4, 2021; Prepublished online: January 18, 2021; Published: March 3, 2021  Show citation

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Elsalem L, Al Sheboul S, Khasawneh A. Synergism between WLBU2 peptide and antibiotics against methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing Enterobacter cloacae. J Appl Biomed. 2021;19(1):14-25. doi: 10.32725/jab.2021.001. PubMed PMID: 34907712.
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