Antibacterial Activity of Surfactin and Synergistic Effect with Conventional Antibiotics Against Methicillin-Resistant Staphylococcus aureus Isolated from Patients with Diabetic Foot Ulcers

Zhaoyinqian Li; Tingting Li; Jingyang Tang; Li Huang; Yinhuan Ding; Zhangrui Zeng; Jinbo Liu

doi:10.2147/DMSO.S435062

Antibacterial Activity of Surfactin and Synergistic Effect with Conventional Antibiotics Against Methicillin-Resistant Staphylococcus aureus Isolated from Patients with Diabetic Foot Ulcers

Diabetes Metab Syndr Obes. 2023 Nov 20:16:3727-3737. doi: 10.2147/DMSO.S435062. eCollection 2023.

Authors

Zhaoyinqian Li^#^{1

2

3}, Tingting Li^#^{1

2

3

4}, Jingyang Tang^{1

2

3}, Li Huang^{1

2

3}, Yinhuan Ding^{1

2

3}, Zhangrui Zeng^{1

2

3}, Jinbo Liu^{1

2

3}

Affiliations

¹ Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China.
² Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Luzhou, People's Republic of China.
³ Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People's Republic of China.
⁴ Department of Laboratory Medicine, West China Fourth Hospital, Sichuan University, Chengdu, People's Republic of China.

^# Contributed equally.

Abstract

Introduction: The prevalence of diabetic foot ulcers (DFUs) is increasing, leading to a huge financial burden and human suffering. Furthermore, antibiotic resistance is an urgent problem in the realm of clinical practice. Antimicrobial peptides are an effective and feasible strategy for combating infections caused by drug-resistant bacteria. Therefore, we investigated the in vitro antimicrobial ability of the lipopeptide surfactin, either alone or in combination with conventional antibiotics, against the standard and clinical strains of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), isolated from patients with DFUs.

Methods: The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of surfactin on the selected strains were evaluated by a microbroth dilution technique. The growth curves of the selected strains with and without surfactin were measured, and transmission electron microscopy was used to observe the structure of surfactin-treated bacterial cells. The biofilm inhibitory abilities of surfactin were assessed by crystal violet staining. The antimicrobial interactions between surfactin and conventional antibiotics were established using a checkerboard assay, as well as determining the mutant prevention concentration. The inhibitory effect of surfactin on penicillinase was tested by iodometry.

Results: The MIC and MBC values of surfactin ranged from 512 to 1024 µg/mL and 1024 to 2048 µg/mL, respectively. Moreover, surfactin significantly prevented the S. aureus biofilm formation and displayed limited toxicity on human red blood cells. The synergies between surfactin and ampicillin, oxacillin, and tetracycline against S. aureus were revealed. In vitro resistance was not readily produced by surfactin. The action of surfactin may be by disrupting bacterial cell membranes and inhibiting penicillinase.

Conclusion: Surfactin appears to be a potential option for the treatment of DFUs infected with MRSA, as it is capable of improving antimicrobial activities and can be used alone or in combination with conventional antibiotics to prevent or postpone the emergence of resistance.

Keywords: antimicrobial peptides; diabetic foot ulcers; methicillin-resistant Staphylococcus aureus; surfactin; synergistic effect.

Grants and funding

This study was supported by the Sichuan Province Science and Technology Support Program (2021YFS0329, 2022YFQ0093) and Luxian Government and Southwest Medical University Cooperation Program (2020LXXNYKD-04).