Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Associated disease: bubonic plague [ICD11: 1B93.0 , ICD11: XN6QS ]; pneumonic plague [ICD11: 1B93.2 , ICD11: XN6QS ]; infection due to Yersinia pestis [ICD11: XN6QS ]
 
Publication DOI: 10.1007/978-90-481-9054-6_8
Publisher: Springer
Editors: Schafferman A, Ordentlich A
Correspondence: a-p-anisimovyandex.ru
Institutions: State Research Center for Applied Microbiology and Biotechnology, Obolensk, 142279, Moscow Region, Russia, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47, Leninskii Prospect, Moscow, Russia, Research Center Borstel, D-23457, Borstel, Germany

Analysis of bacterial genomes revealed the phylogenetic proximity of predicted enzymes responsible for biosynthesis of lipopolysaccharide (LPS) of Yersinia pestis, the cause of plague, to homologous proteins of Yersinia spp. and some distantly related bacteria (Serratia proteamaculans, Erwinia carotovora, Burkholderia dolosa, Photorhabdus luminescens and others). Isogenic Y.pestis strains with single or double mutations in 14 genes of LPS biosynthetic pathways were constructed. Using high-resolution electrospray ionization mass spectrometry, the full LPS structures were elucidated in each mutant, and the sequence of monosaccharide transfers in the assembly of the LPS core was inferred. Truncation of the core decreased significantly the resistance of bacteria to normal human serum (NHS) and polymyxin B. Impairing of LPS biosynthesis resulted also in reduction of LPS-dependent enzymatic activities of plasminogen activator. A gradual truncation of the LPS core was accompanied by a decrease of bacterial virulence in mice and guinea pigs. However, the reduction in virulence remained behind the decrease of bacterial resistance to innate immunity factors. For instance, waaQ mutant deficient in HepIII transferase was highly susceptible to polymyxin B and NHS but was as virulent as the parental strain for both animals. Y.pestis mutants with two or less sugar residues in the LPS core were not only susceptible to antimicrobial cationic peptides and NHS but also avirulent in animal infection models. This finding demonstrated that the LPS structure is critical for the lethality of plague infection, and waaC, hldE and waaA or their protein products can be considered as promising candidates for targeting Y.pestis virulence using specific inhibitors. As the identities of the corresponding enzymes to non-yersiniae protein homologs are less than 90%, it seems possible to fit an inhibitor to each of the targets that will not affect normal commensal microflora in mammalian host.

Lipopolysaccharide, Yersinia pestis, host-pathogen interactions

Structure type: fragment of a bigger structure
Location inside paper: p.80, fig.8.1, p.83, table 8.1, wecA (YPO03866), waaL (YPO0417)
Aglycon: (2->6) lipid A
Compound class: LPS
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_130650,IEDB_130670,IEDB_135607,IEDB_135609,IEDB_136044,IEDB_137472,IEDB_140087,IEDB_140088,IEDB_140090,IEDB_141794,IEDB_142488,IEDB_146664,IEDB_190606,IEDB_2189046,IEDB_2189047,IEDB_226811,IEDB_983931,SB_165,SB_166,SB_187,SB_192,SB_195,SB_7,SB_88
 
Methods: ESI-MS, mild acid hydrolysis, serological methods
Biological activity: biological activity data, coagulase and fibrinolytic activities of plasminogen activator
Enzymes that release or process the structure: wecA,waaL
Comments, role: wecA(YPO03866) and waaL(YPO0417) mutants. Proc. Oholo 2009 Conference 'The Challenge of Highly Pathogenic Microorganisms - Mechanism of Virulence and Novel Medical Countermeasures', October 25-29, 2009, Eilat, Israel
 
Related record ID(s): 25175, 25493, 25494, 25495, 25497, 25498, 25499, 25500, 25940, 25941
NCBI Taxonomy refs (TaxIDs): 632
Show glycosyltransferases
 

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