Chemical Biology Lab (ASK-II-409), School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamilnadu, India.
Medicinal Chemistry and Immunology Lab (ASK-II-406), School of Chemical and Biotechnology (SCBT), SASTRA Deemed University, Thanjavur, India.
Microb Pathog. 2022 Jun;167:105585. doi: 10.1016/j.micpath.2022.105585. Epub 2022 May 13.
Methicillin resistant Staphylococcus aureus (MRSA) is a prime pathogen responsible for various infections in human beings. Expression of virulence factors is a biggest challenge in MRSA, which results in failure of conventional antibiotic therapy. In connection to the search for natural and safe anti-virulence compounds, the present study focused to evaluate the anti-virulence potential of catechin-in-cyclodextrin-in-phospholipid liposome (CCPL) on MRSA strains. CCPL inhibited young biofilm (64.15-72.70%) as well degraded mature biofilm (55.60-63.65%) at ½ and ¼ MIC doses, which was further confirmed by scanning electron microscopy and confocal laser scanning microscope studies. CCPL was capable enough to modify the surface hydrophobicity (40.26-48.59%), reduce the EPS production (1.71-2.25 folds) and bacterial motility. In addition, CCPL inhibited the synthesis of virulence factors like slime production (0.40-0.50 folds), DNase production, hemolytic activity (28.08-49.07%), proteolytic production (14.65-18.04%), lipase production, autolysis and cell auto-aggregation. CCPL prevented the staphyloxanthin production and thereby increased the susceptibility of MRSA strains towards HO. Further, CCPL significantly down-regulated the virulence genes (agrA, agrC, clfA, clfB, fnbA, fnbB, icaA, icaD, hla, hld, rna III, atlA, sarA, sigB & geh). Thus, the results of present study revealed that the CCPL can effectively reduce the virulence properties and its application could inhibit the pathogenicity and also prevents the development of drug-resistance in MRSA strains.
耐甲氧西林金黄色葡萄球菌（MRSA）是导致人类各种感染的主要病原体。毒力因子的表达是 MRSA 面临的最大挑战，导致常规抗生素治疗失败。鉴于寻找天然安全的抗毒力化合物的需要，本研究旨在评估表没食子儿茶素没食子酸酯-环糊精-磷脂脂质体（CCPL）对 MRSA 菌株的抗毒力潜力。CCPL 在半 MIC 和四分之一 MIC 剂量下抑制了年轻生物膜（64.15-72.70%）和成熟生物膜（55.60-63.65%），扫描电子显微镜和共聚焦激光扫描显微镜研究进一步证实了这一点。CCPL 足以改变表面疏水性（40.26-48.59%）、减少 EPS 产生（1.71-2.25 倍）和细菌运动性。此外，CCPL 抑制了毒力因子的合成，如粘液产生（0.40-0.50 倍）、DNase 产生、溶血活性（28.08-49.07%）、蛋白水解产生（14.65-18.04%）、脂肪酶产生、自溶和细胞自聚集。CCPL 阻止了金黄色素的产生，从而增加了 MRSA 菌株对 HO 的敏感性。此外，CCPL 显著下调了毒力基因（agrA、agrC、clfA、clfB、fnbA、fnbB、icaA、icaD、hla、hld、rna III、atlA、sarA、sigB 和 geh）。因此，本研究结果表明，CCPL 可有效降低毒力特性，其应用可抑制 MRSA 菌株的致病性，并防止耐药性的发展。
