Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India.
Department of Microbiology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India.
Int J Biol Macromol. 2018 Apr 15;110:157-166. doi: 10.1016/j.ijbiomac.2018.01.083. Epub 2018 Feb 2.
Lysostaphin (LST) is a bacteriocin that cleaves within the pentaglycine cross bridge of Staphylococcus aureus peptidoglycan. Previous studies have reported the high efficiency of LST even against multi drug resistant S. aureus including methicillin resistant S. aureus (MRSA). In this study, we have developed a new chitosan based hydrogel formulation of LST to exploit its anti-staphylococcal activity. The atomic interactions of LST with chitosan were studied by molecular docking studies. The rheology and the antibacterial properties of the developed LSTC gel were evaluated. The developed LST containing chitosan hydrogel (LSTC gel) was flexible, flows smoothly and remains stable at physiological temperature. The in vitro studies by agar well diffusion and ex vivo studies in porcine skin model exhibited a reduction in S. aureus survival by ∼3 LogCFU/mL in the presence of LSTC gel. The cytocompatibility of the gel was tested in vitro using macrophage RAW 264.7 cell line and in vivo in Drosophila melanogaster. A gradual disruption of S. aureus biofilms with the increase of LST concentrations in the LSTC gel was observed which was confirmed by SEM analysis. We conclude that LSTC gel could be highly effectual and advantageous over antibiotics in treating staphylococcal-topical and biofilm infections.
溶葡萄球菌素（LST）是一种细菌素，可在金黄色葡萄球菌肽聚糖的五肽交联桥上切割。先前的研究报告称，LST 的效率很高，甚至可以对抗包括耐甲氧西林金黄色葡萄球菌（MRSA）在内的多种耐药金黄色葡萄球菌。在这项研究中，我们开发了一种新的壳聚糖基 LST 水凝胶制剂，以利用其抗葡萄球菌活性。通过分子对接研究研究了 LST 与壳聚糖的原子相互作用。评估了开发的 LSTC 凝胶的流变学和抗菌性能。开发的含有 LST 的壳聚糖水凝胶（LSTC 凝胶）具有柔韧性，在生理温度下流畅地流动并保持稳定。琼脂井扩散的体外研究和猪皮模型的体外研究表明，在 LSTC 凝胶存在下，金黄色葡萄球菌的存活率降低了约 3 LogCFU/mL。通过巨噬细胞 RAW 264.7 细胞系在体外和黑腹果蝇在体内测试了凝胶的细胞相容性。随着 LSTC 凝胶中 LST 浓度的增加，逐渐破坏了金黄色葡萄球菌生物膜，这一点通过 SEM 分析得到了证实。我们得出的结论是，与抗生素相比，LSTC 凝胶在治疗葡萄球菌局部和生物膜感染方面可能更有效和有利。
