Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-7613Central Research Institute for Epidemiology14082ArticlesСтатьиReview ArticleMOLECULAR ASPECTS OF ANTHRAX PATHOGENESISМОЛЕКУЛЯРНЫЕ АСПЕКТЫ ПАТОГЕНЕЗА СИБИРСКОЙ ЯЗВЫNoskovA. NНосковА. НGamaleya Research Institute of Epidemiology and Microbiology, Moscow, RussiaНИИ эпидемиологии и микробиологии им. Н.Ф.Гамалеи, Москва15082014914NO4 (2014)№4 (2014)9210109062023Copyright ©; 2014, Noskov A.N.Copyright ©; 2014, Носков А.Н.2014Noskov A.N.Носков А.Н.https://creativecommons.org/licenses/by/4.0https://microbiol.crie.ru/jour/article/view/14082

A model of anthrax infection with the role determined for main pathogenicity factors of Bacillus anthracis exotoxin and capsule is presented. After spore phagocytosis by macrophages, synthesis of the main exotoxin component begins - a protective antigen that in oligomeric form disrupts phagosome membrane. This accelerates the transition of the pathogen from phagosome into the macrophage cytoplasm. Poly-D-glutamine capsule synthesized by the pathogen triggers the exit (exocytosis) of vegetative cells from macrophages and protects them from re-phagocytosis in lymphatic node lumen. The vegetative cells, that actively and freely replicate in lymphatic node, secret an exotoxin that disrupts endothelial septum between lymph and blood due to cytotoxic activity. As a result the vegetative cells get into blood and bacteremia develops. Pathogenetic pattern during anthrax (multiple hemorrhages in various organs etc.) is associated with local microcirculation disorders of various organs caused by the effect of bacterial exoproteases via activation of Willebrand factor. This results in a rapid local increase of microbial mass and consequent powerful cytotoxic effect of exotoxin on the tissue cells of the affected organ. Death of the infected organism takes place at the final stage of infection due to toxic shock caused by the exotoxin. A reduction of body temperature takes place after death and the process of spore formation begins in the dead animal: capsule depolymerization, chain shortening, pep-tidoglycan cortex formation. Spores in this form are the prolonged source of infectious agent conservation and spread of infection in nature.

Представлена модель сибиреязвенной инфекции, в которой определена роль основных факторов патогенности Bacillus anthracis экзотоксина и капсулы. После фагоцитоза спор макрофагами начинается синтез основного компонента экзотоксина - протективного антигена, который в олигомерной форме разрушает фагосомную мембрану. Это ускоряет переход патогена из фагосомы в цитоплазму макрофага. Синтезируемая патогеном поли-D-глютаминовая капсула запускает выход (экзоцитоз) вегетативных клеток из макрофагов и защищает их от рефагоцитоза в просвете лимфатического узла. Вегетативные клетки, активно и беспрепятственно размножаясь в лимфатическом узле, секретируют экзотоксин, который за счет цитотоксического действия разрушает эндотелиальную перегородку между лимфой и кровью. В результате вегетативные клетки попадают в кровь и развивается бактериемия. Патогенетическая картина, наблюдаемая при сибирской язве (многочисленные геморрагии в различных органах и т.п.), связана с локальными нарушениями микроциркуляции различных органов, вызванными действием бактериальных экзопротеаз через активацию фактора Виллебранта. Это приводит к быстрому локальному нарастанию микробной массы и последующему мощному цитотоксическому действию экзотоксина на клетки тканей поражаемого органа. На завершающей стадии инфекции наступает смерть инфицированного организма вследствие вызываемого экзотоксином токсического шока. После смерти инфицированного организма наступает снижение температуры тела и начинается процесс формирования спор в павшем животном: деполимеризация капсулы, укорачивание цепочек, формирование пептидогликанового кортекса. В таком виде споры представляют собой длительный источник сохранения инфекционного агента и распространения инфекции в природе.

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