Kim Sehyeon Erica, Ibarra-Meneses Ana Victoria, Fernandez-Prada Christopher, Huan Tao
Department of Chemistry, Faculty of Science, University of British Columbia, Vancouver Campus, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
Department of Pathology and Microbiology, Faculty of Veterinary Medicine, Université de Montréal, 626 CIMIA Sicotte Street, Saint-Hyacinthe, QC J2S 2M2, Canada.
Metabolites. 2024 Nov 25;14(12):658. doi: 10.3390/metabo14120658.
: The rise of drug-resistant strains presents a significant challenge in the treatment of Leishmaniasis, a neglected tropical disease. Extracellular vesicles (EVs) produced by these parasites have gained attention for their role in drug resistance and host-pathogen interactions. : This study developed and applied a novel lipidomics workflow to explore the lipid profiles of EVs from three types of drug-resistant strains compared to a wild-type strain. EVs were isolated through ultracentrifugation, and their lipid content was extracted using a modified Matyash protocol. LC-MS analysis was performed, and data processing in MS-DIAL enabled lipid identification and quantification. Statistical analysis in MetaboAnalyst revealed strain-specific lipid alterations, highlighting potential links between lipid composition and drug resistance mechanisms. : Our results show distinct alterations in lipid composition associated with drug resistance. Specifically, drug-resistant strains exhibited reduced levels of phosphatidylcholine (PC) and phosphatidylglycerol (PG), particularly in the amphotericin B-resistant strain AmB1000.1. Sterol and glycerolipid species, including cholesteryl ester (CE) and triacylglycerol (TG) were also found to be diminished in AmB1000.1. These changes suggest significant lipid remodeling under drug pressure, potentially altering the biophysical properties of EV membranes and their capacity for molecule transfer. Furthermore, the lipidomic profiles of EVs from the other resistant strains, LiSb2000.1 and LiMF200.5, also displayed unique alterations, underscoring strain-specific adaptations to different drug resistance mechanisms. : These significant alterations in lipid composition suggest potential lipid-based mechanisms underlying drug resistance in , providing new avenues for therapeutic intervention.
耐药菌株的出现给利什曼病（一种被忽视的热带疾病）的治疗带来了重大挑战。这些寄生虫产生的细胞外囊泡（EVs）因其在耐药性和宿主-病原体相互作用中的作用而受到关注。本研究开发并应用了一种新型脂质组学工作流程，以探索三种耐药菌株与野生型菌株相比的EVs脂质谱。通过超速离心分离EVs，并使用改良的Matyash方案提取其脂质含量。进行了液相色谱-质谱（LC-MS）分析，MS-DIAL中的数据处理实现了脂质的鉴定和定量。MetaboAnalyst中的统计分析揭示了菌株特异性的脂质变化，突出了脂质组成与耐药机制之间的潜在联系。我们的结果显示与耐药性相关的脂质组成有明显变化。具体而言，耐药菌株的磷脂酰胆碱（PC）和磷脂酰甘油（PG）水平降低，尤其是在对两性霉素B耐药的菌株AmB1000.1中。在AmB1000.
