Institute of Biosciences, São Paulo State University (UNESP), Campus Botucatu 18618-691, Brazil.
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto 14040-903, Brazil.
J Appl Microbiol. 2023 Feb 16;134(2). doi: 10.1093/jambio/lxac080.
The antibacterial activity of red propolis extract (RPE) and brown propolis extracts (BPE) and the synergistic effect of RPE with cefoxitin (CEFO), imipenem (IMI), and ertapenem (ERTA) was evaluated in vitro against methicillin-resistant Staphylococcus aureus (MRSA) strains.
MRSA ATCC 33591, community-associated (CA-MRSA) USA300, and four clinical isolates were used. A broth microdilution assay was performed to obtain inhibitory and bactericidal concentrations of BPE, RPE, CEFO, IMI, and ERTA. RPE in combination with CEFO, IMI, and ERTA was evaluated on the formation or eradication of biofilm. The bacterial relative membrane conductivity of the strains was assessed after RPE and combinations exposition. Surface/binding computational analyzes between RPE compounds and penicillin binding protein 2a (PBP2a) were performed. BPE samples had no activity against MRSA (MICs 3.2-5 g l-1; MBCs 10-15 g l-1), so the subsequent assays were carried out only with RPE and antimicrobials. RPE exerted a bacteriostatic action (MICs 0.0156-0.125 g l-1; MBCs 0.5-2 g l-1) but the combinations with IMI and ERTA showed the highest inhibition, as observed in the time-kill curve. However, the FICI index showed synergism (≥0.5) only to RPE + IMI. This combination was the most effective in inhibiting the biofilm and showed the highest values of membrane conductivity. Computational predictions indicated that RPE constituents may interact with PBP2a.
RPE and RPE + IMI exerted an antibacterial and antibiofilm activity on MRSA strains probably due to membrane/wall damage and interactions with PBP2a.
评估红色蜂胶提取物（RPE）和棕色蜂胶提取物（BPE）的抗菌活性，以及 RPE 与头孢西丁（CEFO）、亚胺培南（IMI）和厄他培南（ERTA）联合使用对耐甲氧西林金黄色葡萄球菌（MRSA）菌株的协同作用。
使用了 MRSA ATCC 33591、社区获得性（CA-MRSA）USA300 和四个临床分离株。通过肉汤微量稀释法测定 BPE、RPE、CEFO、IMI 和 ERTA 的抑菌和杀菌浓度。评估了 RPE 与 CEFO、IMI 和 ERTA 联合使用对生物膜形成或清除的影响。在暴露于 RPE 和组合后，评估了菌株的细菌相对膜电导率。对 RPE 化合物与青霉素结合蛋白 2a（PBP2a）之间的表面/结合进行了计算分析。BPE 样品对 MRSA 无活性（MICs 3.2-5 g/l；MBCs 10-15 g/l），因此后续试验仅使用 RPE 和抗菌药物进行。RPE 表现出抑菌作用（MICs 0.0156-0.125 g/l；MBCs 0.5-2 g/l），但与 IMI 和 ERTA 的组合显示出最高的抑制作用，如时间杀伤曲线所示。然而，FICI 指数显示协同作用（≥0.5）仅对 RPE+IMI。该组合在抑制生物膜方面最为有效，显示出最高的膜电导率值。计算预测表明，RPE 成分可能与 PBP2a 相互作用。
RPE 和 RPE+IMI 对 MRSA 菌株表现出抗菌和抗生物膜活性，可能是由于膜/细胞壁损伤以及与 PBP2a 的相互作用。
