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СAPSULAR ANTIGEN OF YERSINIA PESTIS

By L. A. Kadnikova, P. K. Kopylov, S. V. Dentovskaya and A. P. Anisimov

Abstract

<p class="p1"><span class="s1">Plague is a zoonosis caused by gram-negative bacteria <em>Yersinia pestis</em>, which, as a rule, is transmitted to humans from septicemic rodents by the bites of infected fleas. This microbe killed more people than all of the wars in the human history. <em>Y. pestis </em>circulation in the natural plague foci is ensured by the whole number of pathogenicity factors with differing functional orientation. This review is devoted to one of them, <em>Y. pestis </em>capsular antigen (F1 or Caf1). The history of its discovery and studying of its genetic control, biosynthesis, isolation and purification, and physicochemical properties are reviewed. Its roles in plague pathogenesis and its application as a main component of plague vaccines are also discussed. <em>Y. pestis </em>capsule under light microscopy is visually amorphous, while high-resolution electron microscopy displays the structure formed from separate fimbria-like cords up to 200 nm long, diverging from the bacterial surface in different directions. At 37</span><span class="s2">°</span><span class="s1">C <em>Y. pestis </em>produce 800–1000 times more capsular antigen than at 28</span><span class="s2">°</span><span class="s1">C. Genes coding for 17.6-kD Caf1 protein, which contains 170 amino acids, are located in <em>caf1 </em>operon of pFra plasmid. Analysis of <em>caf1 </em>operon nucleotide sequence testified its close phylogenetic relationship with the gene clusters coding for pilus adhesins that were secreted with the help of chaperone/usher systems in enterobacteria including six additional adhesins in <em>Y. pestis</em>. <em>Y. pestis </em>multiplication within macrophages is the obligatory stage of plague pathogenesis, and the plague pathogen virulence correlates not with resistance to phagocyte ingesting but with bacterial ability to survive and multiply within phagolysosomes of phagocytes due to neutralization of antibacterial functions of eukaryotic cells. The capsule formed out of the Caf1 aggregates protects <em>Y. pestis </em>from ingestion by na</span><span class="s3">ï</span><span class="s1">ve host’s phagocytes and prevents from initiation of the alternative pathway of the complement system. Molecular usher Caf1A responsible for capsular antigen anchoring on the surface of bacterial cell has a high affinity to human interleukin 1</span><span class="s2">β</span><span class="s1">. Caf1 can compete with interleukins 1</span><span class="s2">α</span><span class="s1">, 1</span><span class="s2">β</span><span class="s1">, and 1ra in binding to receptors on lymphoid cells preventing development of adequate immune response. Immunodiagnosis of plague is based on detection of Caf1 or anti-Caf1 antibodies since this <em>Y. pestis </em>antigen is species specific. Covering bacterial surfaces capsular antigen is also the paramount component of all modern plague vaccines. Its leading role in induction of intense immunity in mice, rats, monkeys, and men was shown clearly. However, non-capsulated (Caf1</span><span class="s4">–</span><span class="s1">) variants of <em>Y. pestis </em>keeping their virulence at the level of the wild-type strains might be selected and accumulated in immune animals. This indicates inadmissibility of application of monoantigen plague vaccines and necessity for design of immunoprophylactic preparations aimed at two or three molecular targets. </span></p

Topics: Yersinia pestis, капсульный антиген, F1, Caf, фактор патогенности, патогенез, иммуногенез, чума, Infectious and parasitic diseases, RC109-216
Publisher: Sankt-Peterburg : NIIÈM imeni Pastera
Year: 2015
OAI identifier: oai:doaj.org/article:a254f5a315ca47f68ca189bc55f07128
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