Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: plague [ICD11:
1B93 
, ICD11:
XN6QS ];
infection due to Yersinia pestis [ICD11:
XN6QS ]
NCBI PubMed ID: 32868431Publication DOI: 10.1073/pnas.1917504117Journal NLM ID: 7505876Publisher: National Academy of Sciences
Correspondence: rkernst
umaryland.edu
Institutions: Department of Microbial Pathogenesis, University of Maryland, Baltimore, MD 21201, Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand 10700, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201, Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011, International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland 80-822, Department of Molecular Biosciences, University of Texas, Austin, TX 78712, Institute for Genome Sciences, University of Maryland, Baltimore, MD 21201, Department of Infectious Diseases, University of Georgia, Athens, GA 30602, Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada L8S4L8
Immune evasion through membrane remodeling is a hallmark of Yersinia pestis pathogenesis. Yersinia remodels its membrane during its life cycle as it alternates between mammalian hosts (37 °C) and ambient (21 °C to 26 °C) temperatures of the arthropod transmission vector or external environment. This shift in growth temperature induces changes in number and length of acyl groups on the lipid A portion of lipopolysaccharide (LPS) for the enteric pathogens Yersinia pseudotuberculosis (Ypt) and Yersinia enterocolitica (Ye), as well as the causative agent of plague, Yersinia pestis (Yp). Addition of a C16 fatty acid (palmitate) to lipid A by the outer membrane acyltransferase enzyme PagP occurs in immunostimulatory Ypt and Ye strains, but not in immune-evasive Yp Analysis of Yp pagP gene sequences identified a single-nucleotide polymorphism that results in a premature stop in translation, yielding a truncated, nonfunctional enzyme. Upon repair of this polymorphism to the sequence present in Ypt and Ye, lipid A isolated from a Yp pagP+ strain synthesized two structures with the C16 fatty acids located in acyloxyacyl linkage at the 2' and 3' positions of the diglucosamine backbone. Structural modifications were confirmed by mass spectrometry and gas chromatography. With the genotypic restoration of PagP enzymatic activity in Yp, a significant increase in lipid A endotoxicity mediated through the MyD88 and TRIF/TRAM arms of the TLR4-signaling pathway was observed. Discovery and repair of an evolutionarily lost lipid A modifying enzyme provides evidence of lipid A as a crucial determinant in Yp infectivity, pathogenesis, and host innate immune evasion.
Pathogenesis, lipid A, Yersinia, evolution, immune evasion
Structure type: oligomer ; 1404
Location inside paper: fig.1A, Y. pestis
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531
Methods: chemical analysis, TLC, GC, statistical analysis, cloning, bioinformatic analysis, ESI-LTQ-MS, GC-FID, SEM, cell stimulations
Comments, role: tetracyl form of lipid A from Y. pestis grown at 37°C.
Related record ID(s): 3320, 3321, 3322, 3323, 3324
NCBI Taxonomy refs (TaxIDs): 632
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
report error