Mund Sai Sarbani, Chakraborty Sourabrata, Mukherjee Chandrachur, Sahu Khageswar, Majumder Shovan Kumar
Applied Photobiology and Microbiology Section, Laser Biomedical Applications Division, Raja Ramanna Centre for Advanced Technology, Madhya Pradesh, Indore, 452013, India.
Homi Bhaba National Institute, Training School Hostel Complex, Anushakti Nagar, Mumbai, 400094, India.
Probiotics Antimicrob Proteins. 2025 May 22. doi: 10.1007/s12602-025-10558-7.
Infections caused by antimicrobial drug-resistant (AMR) pathogens like methicillin-resistant Staphylococcus aureus (MRSA) have triggered global scale search for innovative, clinically viable and cost affordable alternatives that do not generate resistance. Antimicrobial photodynamic therapy (aPDT) and postbiotics are innovative alternatives to circumvent AMR pathogens. However, MRSA biofilms reduce microbial susceptibility to aPDT and postbiotics. Integrating both modalities can be a novel MRSA anti-biofilm therapeutics avenue, but further studies are needed to validate the efficacy and applicability. We investigated the potentiality of methylene blue (MB)-mediated aPDT (MB-aPDT) followed by Lactobacillus acidophilus-derived cell-free supernatant (LA-CFS) treatment on MRSA planktonic culture, pre-formed biofilms, biofilm initiation, and maturation. Compared to aPDT or LA-CFS monotherapy, MB-aPDT followed by LA-CFS (20 and 40% v/v) treatment for 2 h leads to augmentation in inactivation of MRSA planktonic culture and CFU data correlates with flow cytometry data (R = 0.87). Atomic force microscopy (AFM) unravels different pattern of morphological alterations elicited by aPDT or LA-CFS, but extensive cellular damage and cell fragmentation results from the combinatorial treatment. The determinants of LA-CFS-based augmented action seem to be pH labile. Further, destruction of preformed biofilm shows the following trend: aPDT < LA-CFS < aPDT + LA-CFS. Furthermore, MRSA surviving LA-CFS or aPDT can either adhere to the substratum or form loose biofilms, respectively, but the combinatorial regimen remarkably inhibits adherence and subsequent biofilm initiation, as well as maturation. The augmentation of MRSA inactivation using aPDT-postbiotics can be a new therapeutic avenue for the management of MRSA biofilm-associated infections.
由耐抗菌药物（AMR）病原体如耐甲氧西林金黄色葡萄球菌（MRSA）引起的感染，引发了全球范围内对创新、临床可行且成本可承受的无耐药性替代方案的探索。抗菌光动力疗法（aPDT）和后生元是规避AMR病原体的创新替代方案。然而，MRSA生物膜会降低微生物对aPDT和后生元的敏感性。将这两种方式结合可能是一种新型的MRSA抗生物膜治疗途径，但需要进一步研究来验证其疗效和适用性。我们研究了亚甲蓝（MB）介导的aPDT（MB-aPDT）联合嗜酸乳杆菌无细胞上清液（LA-CFS）处理对MRSA浮游培养物、预先形成的生物膜、生物膜起始和成熟的影响。与aPDT或LA-CFS单一疗法相比，MB-aPDT联合LA-CFS（20%和40% v/v）处理2小时可增强MRSA浮游培养物的灭活，CFU数据与流式细胞术数据相关（R = 0.87）。原子力显微镜（AFM）揭示了aPDT或LA-CFS引起的不同形态改变模式，但联合处理导致广泛的细胞损伤和细胞破碎。基于LA-CFS的增强作用的决定因素似乎对pH不稳定。此外，对预先形成的生物膜的破坏呈现以下趋势：aPDT < LA-CFS < aPDT + LA-CFS。此外，在LA-CFS或aPDT处理后存活的MRSA分别可以粘附在基质上或形成松散的生物膜，但联合治疗方案显著抑制粘附以及随后的生物膜起始和成熟。使用aPDT-后生元增强MRSA灭活可能是管理MRSA生物膜相关感染的一种新的治疗途径。
