Sevim Akan Handan, Şahal Gülcan, Karaca Tuğçe Deniz, Gürpınar Özer Aylin, Maraş Meltem, Doğan Alev
Department Biology, Faculty of Science, Hacettepe University, Beytepe, Cankaya, 06800, Ankara, Turkey.
Department of Medical Services and Techniques, Gazi University Health Service Vocational School, Ankara, Turkey.
Arch Microbiol. 2023 Oct 31;205(12):365. doi: 10.1007/s00203-023-03724-4.
Antibacterial resistance and cancer are worldwide challenges and have been defined as major threats by international health organizations. Peptides are produced naturally by all organisms and have a variety of immunomodulatory, physiological, and wound-healing properties. They can also provide protection against microorganisms and tumor cells. Therefore, we aimed to determine the antimicrobial, antibiofilm, and anticancer potentials of Glycyl-Arginine and Lysyl-Aspartic acid dipeptides. The Broth Dilution and Crystal Violet Binding assays assessed the antimicrobial tests and biofilm inhibitory effects. The MTT assay was used to measure the cytotoxic effects of dipeptides on HeLa cell viability. According to our results, Candida tropicalis T26 and Proteus mirabilis U15 strains were determined as more resistant to Staphylococcus epidermidis W17 against Glycyl-Arginine and Lysyl-Aspartic acid dipeptides with MICs higher than 2 mM (1 mg/mL). Sub-MICs of Glycyl-Arginine caused inhibitions against biofilm formation of all the tested clinical isolates, with the highest inhibition observed against S. epidermidisW17. Lysyl-Aspartic acid exhibited zero to no effect against biofilm formation of P. mirabilisU15, and S. epidermidisW17, whereas it exhibited 52% inhibition of biofilm formation of C. tropicalisT26. Cell viability results revealed that HeLa cell viability decreases with increasing concentration of both dipeptides. Also, parallel to antimicrobial tests, Glycyl-Arginine has a greater cytotoxic effect compared to Lysyl-Aspartic acid. The findings from this study will contribute to the advancement of novel strategies involving dipeptide-based synthesizable molecules and drug development studies. However, it is essential to note that there are still challenges, including the need for extensive experimental and clinical trials.
抗菌耐药性和癌症是全球性挑战，已被国际卫生组织界定为重大威胁。肽由所有生物体天然产生，具有多种免疫调节、生理和伤口愈合特性。它们还能提供针对微生物和肿瘤细胞的保护作用。因此，我们旨在确定甘氨酰 - 精氨酸和赖氨酰 - 天冬氨酸二肽的抗菌、抗生物膜和抗癌潜力。肉汤稀释法和结晶紫结合试验评估了抗菌测试和生物膜抑制作用。MTT 试验用于测量二肽对 HeLa 细胞活力的细胞毒性作用。根据我们的结果，热带假丝酵母 T26 和奇异变形杆菌 U15 菌株对表皮葡萄球菌 W17 而言，对甘氨酰 - 精氨酸和赖氨酰 - 天冬氨酸二肽的耐药性更强，其最低抑菌浓度高于 2 mM（1 mg/mL）。甘氨酰 - 精氨酸的亚最低抑菌浓度对所有测试临床分离株的生物膜形成均有抑制作用，对表皮葡萄球菌 W17 的抑制作用最为显著。赖氨酰 - 天冬氨酸对奇异变形杆菌 U15 和表皮葡萄球菌 W17 的生物膜形成没有影响，而对热带假丝酵母 T26 的生物膜形成有 52% 的抑制作用。细胞活力结果显示，HeLa 细胞活力随着两种二肽浓度的增加而降低。此外，与抗菌测试结果相似，甘氨酰 - 精氨酸比赖氨酰 - 天冬氨酸具有更强的细胞毒性作用。本研究结果将有助于推进基于二肽的可合成分子和药物开发研究新策略。然而，必须指出的是，仍然存在挑战，包括需要进行广泛的实验和临床试验。
