Untargeted lipidomic analysis to broadly characterize the effects of pathogenic and non-pathogenic staphylococci on mammalian lipids

• Published in: PloS one Vol. 13; no. 10; p. e0206606
• Main Authors: Gajenthra Kumar, Naren, Contaifer, Daniel, Baker, Paul RS, Ekroos, Kim, Jefferson, Kimberly K., Wijesinghe, Dayanjan S.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.10.2018; Public Library of Science (PLoS)
• Subjects: Animals; Antibacterial agents; Antibiotic resistance; Antibiotics; Antiinfectives and antibacterials; Bacteria; Bacterial diseases; Biology and Life Sciences; Cattle; Clinical isolates; Drug therapy; Endocarditis; Enzymes; Fatty acids; Glycerol; Immunology; Infections; Internet; Lipid metabolism; Lipid Metabolism - physiology; Lipids; Mammals; Mass spectrometry; Medicine and Health Sciences; Metabolism; Myocardium - metabolism; Pathogenesis; Pharmacy; Scientific imaging; Species; Staphylococcus - metabolism; Staphylococcus aureus; Staphylococcus infections; Strains (organisms); Virulence; United States > US; Virginia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0206606

Modification of the host lipidome via secreted enzymes is an integral, but often overlooked aspect of bacterial pathogenesis. In the current era of prevalent antibiotic resistance, knowledge regarding critical host pathogen lipid interactions has the potential for use in developing novel antibacterial agents. While most studies to date on this matter have focused on specific lipids, or select lipid classes, this provides an incomplete picture. Modern methods of untargeted lipidomics have the capacity to overcome these gaps in knowledge and provide a comprehensive understanding of the role of lipid metabolism in the pathogenesis of infections. In an attempt to determine the role of lipid modifying enzymes produced by staphylococci, we exposed bovine heart lipids, a standardized model for the mammalian lipidome, to spent medium from staphylococcal cultures, and analyzed lipid molecular changes by MS/MSALL shotgun lipidomics. We elucidate distinct effects of different staphylococcal isolates, including 4 clinical isolates of the pathogenic species Staphylococcus aureus, a clinical isolate of the normally commensal species S. epidermidis, and the non-pathogenic species S. carnosus. Two highly virulent strains of S. aureus had a more profound effect on mammalian lipids and modified more lipid classes than the other staphylococcal strains. Our studies demonstrate the utility of the applied untargeted lipidomics methodology to profile lipid changes induced by different bacterial secretomes. Finally, we demonstrate the promise of this lipidomics approach in assessing the specificity of bacterial enzymes for mammalian lipid classes. Our data suggests that there may be a correlation between the bacterial expression of lipid-modifying enzymes and virulence, and could facilitate the guided discovery of lipid pathways required for bacterial infections caused by S. aureus and thereby provide insights into the generation of novel antibacterial agents.