Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles
Shahan Syed,
Eija Nissilä,
Hanna Ruhanen,
Satoshi Fudo,
Meztlli O. Gaytán,
Sanna P. Sihvo,
Martina B. Lorey,
Jari Metso,
Katariina Öörni,
Samantha J. King,
Oommen P. Oommen,
Matti Jauhiainen,
Seppo Meri,
Reijo Käkelä,
Karita Haapasalo
Affiliations
Shahan Syed
Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland
Eija Nissilä
Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland
Hanna Ruhanen
Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland; Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute for Life Science (HiLIFE) and Biocenter Finland, Helsinki 00014, Finland
Satoshi Fudo
Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland
Meztlli O. Gaytán
Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA
Sanna P. Sihvo
Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland; Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute for Life Science (HiLIFE) and Biocenter Finland, Helsinki 00014, Finland
Martina B. Lorey
Wihuri Research Institute, 00290 Helsinki, Finland
Jari Metso
Minerva Foundation Institute for Medical Research, Biomedicum, 00290 Helsinki, Finland; Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland
Katariina Öörni
Wihuri Research Institute, 00290 Helsinki, Finland
Samantha J. King
Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA; Department of Pediatrics, The Ohio State University, Columbus, OH 43210, USA
Oommen P. Oommen
Bioengineering and Nanomedicine Lab, Faculty of Medicine and Health Technology and BioMediTech Institute, Tampere University, 33720 Tampere, Finland
Matti Jauhiainen
Minerva Foundation Institute for Medical Research, Biomedicum, 00290 Helsinki, Finland; Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland
Seppo Meri
Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland
Reijo Käkelä
Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland; Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute for Life Science (HiLIFE) and Biocenter Finland, Helsinki 00014, Finland
Karita Haapasalo
Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland; Corresponding author
Summary: High-density lipoproteins (HDLs) are a group of different subpopulations of sialylated particles that have an essential role in the reverse cholesterol transport (RCT) pathway. Importantly, changes in the protein and lipid composition of HDLs may lead to the formation of particles with reduced atheroprotective properties. Here, we show that Streptococcus pneumoniae pneumolysin (PLY) and neuraminidase A (NanA) impair HDL function by causing chemical and structural modifications of HDLs. The proteomic, lipidomic, cellular, and biochemical analysis revealed that PLY and NanA induce significant changes in sialic acid, protein, and lipid compositions of HDL. The modified HDL particles have reduced cholesterol acceptor potential from activated macrophages, elevated levels of malondialdehyde adducts, and show significantly increased complement activating capacity. These results suggest that accumulation of these modified HDL particles in the arterial intima may present a trigger for complement activation, inflammatory response, and thereby promote atherogenic disease progression.
