Narang Anmol, Kaur Kirandeep, Bedi Neena, Rajput Neha, Kaur Gagandeep, Kaur Sukhraj
Department of Microbiology, Guru Nanak Dev University, Amritsar, India.
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.
Probiotics Antimicrob Proteins. 2025 May 2. doi: 10.1007/s12602-025-10565-8.
Recalcitrant wounds in diabetic patients are difficult to treat and often require debridement and surgical intervention. Methicillin-resistant Staphylococcus aureus (MRSA), a common pathogen isolated from the diabetic wounds, further delays healing. This study investigates the wound-healing properties of the postbiotics of Lactiplantibacillus plantarum 2034 in MRSA-infected diabetic rats. Ethyl acetate extract (EAE) of L. plantarum was prepared, and its antimicrobial and antibiofilm properties against various pathogens were determined. EAE exhibited broad spectrum antimicrobial activity against various Gram-positive and Gram-negative bacterial pathogens including MRSA. At sub-MIC concentration, EAE inhibited biofilm formation by various pathogens, resulting in maximum inhibition of 82.6% for Bacillus subtilis, 73% for MRSA, and 43% for Salmonella typhi. At MBC concentration, EAE successfully disrupted preformed biofilms of the pathogens, probably due to interference with quorum sensing as shown by its ability to inhibit violacein pigment production by a biosensor Chromobacterium violaceum CV026. Carbopol 934 gel of EAE was formulated and applied to MRSA-infected wounds in diabetic rats. EAE gel showed significant (P < 0.05) reduction in the counts of MRSA on day 4 and complete clearance by day 12. EAE-treated wounds showed significantly (P < 0.05) faster wound closure rate compared to the untreated and standard drug-treated wounds. Histological analysis showed restoration of normal architecture of skin in EAE-treated wounds compared to the untreated and standard drug-treated groups. Furthermore, EAE treatment normalised the mRNA expression of proinflammatory cytokine interleukin (IL)-6 and doubled the levels of anti-inflammatory cytokine IL-10 compared to the untreated control. In conclusion, the dual antimicrobial and anti-inflammatory properties of the EAE gel make it a strong candidate for treating chronic MRSA-infected diabetic wounds. Gas chromatography-mass spectrometry analysis of EAE revealed the presence of several antimicrobial and antioxidant compounds.
糖尿病患者的顽固性伤口难以治疗，通常需要清创和手术干预。耐甲氧西林金黄色葡萄球菌（MRSA）是从糖尿病伤口中分离出的常见病原体，会进一步延缓伤口愈合。本研究调查了植物乳杆菌2034的后生元对MRSA感染的糖尿病大鼠的伤口愈合特性。制备了植物乳杆菌的乙酸乙酯提取物（EAE），并测定了其对各种病原体的抗菌和抗生物膜特性。EAE对包括MRSA在内的各种革兰氏阳性和革兰氏阴性细菌病原体表现出广谱抗菌活性。在亚最小抑菌浓度下，EAE抑制了各种病原体的生物膜形成，对枯草芽孢杆菌的最大抑制率为82.6%，对MRSA为73%，对伤寒沙门氏菌为43%。在最小杀菌浓度下，EAE成功破坏了病原体预先形成的生物膜，这可能是由于其干扰群体感应，如它能够抑制生物传感器紫色色杆菌CV026产生紫色菌素色素所示。将EAE的卡波姆934凝胶制剂应用于MRSA感染的糖尿病大鼠伤口。EAE凝胶在第4天显著（P < 0.05）降低了MRSA的数量，并在第12天完全清除。与未治疗和标准药物治疗的伤口相比，EAE治疗的伤口显示出显著（P < 0.05）更快的伤口闭合率。组织学分析表明，与未治疗和标准药物治疗组相比，EAE治疗的伤口皮肤正常结构得以恢复。此外，与未治疗的对照组相比，EAE治疗使促炎细胞因子白细胞介素（IL）-6的mRNA表达正常化，并使抗炎细胞因子IL-10的水平增加了一倍。总之，EAE凝胶的双重抗菌和抗炎特性使其成为治疗慢性MRSA感染的糖尿病伤口的有力候选药物。EAE的气相色谱-质谱分析揭示了几种抗菌和抗氧化化合物的存在。
