Adhesins of human pathogens from the genus Yersinia.

Bacteria of the Gram-negative genus Yersinia are environmentally ubiquitous. Three species are of medical importance: the intestinal pathogens Y. enterocolitica and Y. pseudotuberculosis, and the plague bacillus Y. pestis. The two former species, spread by contaminated food or water, cause a range of gastrointestinal symptoms and, rarely, sepsis. On occasion, the primary infection is followed by autoimmune sequelae such as reactive arthritis. Plague is a systemic disease with high mortality. It is a zoonosis spread by fleas, or more rarely by droplets from individuals suffering from pneumonic plague. Y. pestis is one of the most virulent of bacteria, and recent findings of antibiotic-resistant strains together with its potential use as a bioweapon have increased interest in the species. In addition to being significant pathogens in their own right, the yersiniae have been used as model systems for a number of aspects of pathogenicity. This chapter reviews the molecular mechanisms of adhesion in yersiniae. The enteropathogenic species share three adhesins: invasin, YadA and Ail. Invasin is the first adhesin required for enteric infection; it binds to ß(1) integrins on microfold cells in the distal ileum, leading to the ingestion of the bacteria and allows them to cross the intestinal epithelium. YadA is the major adhesin in host tissues. It is a multifunctional protein, conferring adherence to cells and extracellular matrix components, serum and phagocytosis resistance, and the ability to autoagglutinate. Ail has a minor role in adhesion and serum resistance. Y. pestis lacks both invasin and YadA, but expresses several other adhesins. These include the pH 6 antigen and autotransporter adhesins. Also the plasminogen activator of Y. pestis can mediate adherence to host cells. Although the adhesins of the pathogenic yersiniae have been studied extensively, their exact roles in the biology of infection remain elusive.

Requirement of the Yersinia pseudotuberculosis effectors YopH and YopE in colonization and persistence in intestinal and lymph tissues.

The gram-negative enteric pathogen Yersinia pseudotuberculosis employs a type III secretion system and effector Yop proteins that are required for virulence. Mutations in the type III secretion-translocation apparatus have been shown to cause defects in colonization of the murine cecum, suggesting roles for one or more effector Yops in the intestinal tract. To investigate this possibility, isogenic yop mutant strains were tested for their ability to colonize and persist in intestinal and associated lymph tissues of the mouse following orogastric inoculation. In single-strain infections, a yopHEMOJ mutant strain was unable to colonize, replicate, or persist in intestinal and lymph tissues. A yopH mutant strain specifically fails to colonize the mesenteric lymph nodes, but yopE and yopO mutant strains showed only minor defects in persistence in intestinal and lymph tissues. While no single Yop was found to be essential for colonization or persistence in intestinal tissues in single-strain infections, the absence of both YopH and YopE together almost eliminated colonization of all tissues, indicating either that these two Yops have some redundant functions or that Y. pseudotuberculosis employs multiple strategies for colonization. In competition infections with wild-type Y. pseudotuberculosis, the presence of wild-type bacteria severely hindered the ability of the yopH, yopE, and yopO mutants to persist in many tissues, suggesting that the wild-type bacteria either fills colonization niches or elicits host responses that the yop mutants are unable to withstand.

Clinical role for a superantigen in Yersinia pseudotuberculosis infection.

Yersinia pseudotuberculosis is an enteric pathogen that causes a variety of clinical symptoms in the human. Recently, we reported the production of a superantigen (Y. pseudotuberculosis-derived mitogen, YPM) by this organism and characterized the gene structure of ypm. To further study the potential pathogenic role of YPM in Y. pseudotuberculosis infection, we assayed IgG anti-YPM antibodies and T cell antigen receptor-Vbeta expression of the T cells in peripheral blood and in mesenteric lymph node in patients acutely infected with Y. pseudotuberculosis. 20 out of 33 patients (61%) had an elevated antibody titer compared with healthy controls (P = 0.0001). Patients with systemic symptoms such as lymphadenopathy, transient renal dysfunction, and arthritis had significantly higher titers of anti-YPM than patients with gastrointestinal tract symptoms alone. T cells bearing the Vbeta3 gene segment were significantly increased (P = 0.009) among acute phase patients compared with healthy children. During the convalescence phase of the illness, there was a reduction in the abnormal level of Vbeta3 T cells. Moreover, in the mesenteric lymph node, an elevated level of Vbeta3 T cells compared with peripheral blood and a sequence diversity in the junctional region of the T cell antigen receptor beta-chain containing Vbeta3 element was observed in one patient. Together, these findings suggest that YPM was produced in vivo and played an important role in the pathogenesis of Y. pseudotuberculosis infection.

[The role of the outer-membrane antigens of Yersinia pseudotuberculosis in the pathogenesis and diagnosis of pseudotuberculosis]. / Rol' antigenov naruzhnoi membrany Yersinia pseudotuberculosis v patogeneze i diagnostike psevdotuberkuleza.

The degree of manifestation of the virulent properties of Y. pseudotuberculosis strains was found to be directly related to the concentration of protein with a mol. wt. of 103 kD (invasin), localized in the outer membrane and necessary for the realization of the process of the penetration of the infective agent into eukaryotic cells. Antiserum to INV-2-BSA, an active synthetic fragment of invasin, capable of detecting one antigenic band with a mol. wt. of 103 kD, was used for the creation of a diagnostic enzyme immunoassay system. The new variant of the diagnostic system was shown to be highly effective in the diagnosis of the disease at an early period.

[The role of the complement system in the pathogenesis of yersinioses]. / Rol' sistemy komplementa v patogeneze iersiniozov.

In 95 patients with Yersinia infections (yersiniosis and pseudotuberculosis) the character of changes in the complement system was studied, taking into account the functional activity of C1-C5, Co. The study demonstrated a decrease in the activity of the complement system in the dynamics of Yersinia infections and revealed quantitative changes of characteristics in yersiniosis and pseudotuberculosis. The results of the study suggest the mobilization of the complement system in Yersinia infections by the classical path of activation. Regularities of changes in the activity of C1-C5, Co, corresponding to the severity and clinical variants of Yersinia infections, make it possible to recommend the use of the above-mentioned parameters in the clinic of infectious diseases for evaluating the effectiveness of treatment and the course of the disease.

[The pathogenetic importance of Yersinia pseudotuberculosis lipopolysaccharide]. / Patogeneticheskoe znachenie lipopolisakharida Yersinia pseudotuberculosis.

The immunogenic and immunomodulating properties of Y. pseudotuberculosis lipopolysaccharide (LPS) with a view to the evaluation of its role in the pathogenesis of Y. pseudotuberculosis infection were studied. The study revealed the importance of LPS as immunogen, the degree of its immunogenicity for laboratory animals and interstrain differences in the response of mice to LPS in the course of immune processes. The role of the immunomodulating activity of LPS with respect to humoral and cellular immunity factors was shown in pathogenesis. Special attention was paid to the stimulating action of LPS on the phagocytic function of macrophages. The hypothetic scheme of the participation of LPS in the pathogenesis of Y. pseudotuberculosis experimental infection was presented.

[Immune complexes and R-proteins in yersinioses]. / Immunnye kompleksy i R-belki pri iersiniozakh.

The intensity of the catabolism of cell receptors in yersiniosis patients has been studied. The dynamics of R-protein level reflects the relapsing character of the pathological process irrespective of the presence of clinically pronounced relapses and the form of the disease. The concentration of circulating immune complexes is elevated during the whole course of the disease and does not depend on its gravity and clinical form. The spectrum of immune complexes in the blood sera of yersiniosis patients is heterogeneous and changes in the course of the disease.

Fatores contemporâneos que afetam a incidência de patógenos causadores de doenças de origem alimentar / Contemporary factors that affect the incidence of foodborne pathogens

A modernizaçäo da sociedade e os avanços na tecnologia alimentar resultaram em mudanças na formulaçäo, produçäo e distribuiçäo dos alimentos criando, consequentemente, situaçöes anteriormente imprevistas, que se constituem em novos desafios microbiológicos. Inúmeros fatores inter-relacionados contribuem para agravar o risco de doenças de origem alimentar, dentre os quais se destacam, as inovaçöes na agropecuária, mudanças nos hábitos alimentares e o aumento da suscetibilidade a infecçöes. Esta revisäo focaliza a situaçäo atual das doenças de origem alimentar, considerando os principais agentes, os fatores de risco e a importância da conscientizaçäo da populaçäo para a prevençäo de surtos epidêmicos.

[Reactive arthritis: terminology, etiology and pathogenesis]. / Reaktivnye artrity: terminologiia, etiologiia, patogenez.

Different serovars of Y. enterocolitica, Y. pseudotuberculosis, Acinetobacter calcoaceticus, and Pseudomonas pauimobilis were isolated from the synovial fluid of 23 out of 34 patients with Yersinia-triggered arthritis by a new bacteriological method based on the selection of the optimal conditions for microorganism culturing; in some cases the strains were isolated repeatedly. The authors discuss the necessity of correcting the previous notions on the aseptic nature of reactive arthritis.

Report of four cases of Yersinia pseudotuberculosis septicemia and a literature review.

Yersinia pseudotuberculosis is a rare cause of disease in humans, the most common manifestation being mesenteric lymphadenitis accompanied by abdominal pain and fever. A septicemic form of Yersinia pseudotuberculosis infection has been reported only rarely. It is usually seen in patients with underlying disorders such as diabetes, hepatic cirrhosis or iron overload. Fifty-four cases of septicemic infection were found in the literature. The earlier published cases are reviewed, and four cases occurring in Finland during the period February to June 1992 are reported.

Responsiveness of susceptible inbred mice to Yersinia pseudotuberculosis serovar III infection.

The susceptibility of BALB/c, C57BL and BDF1-hybrid mouse strains to Yersinia pseudotuberculosis serovar III infection was studied. The bacterial load in the viscera and brain and the host responses at different levels, i.e. blood, peritoneal cavity and organs were determined. Blood cell parameters and peritoneal exudate cell population were evaluated during the infection using the automated hematologic analyzer Technicon H-1. It was found that BDF1-hybrid mice produced an early peritoneal inflammatory response, while in BALB/c and C57BL mice it was not observed. The high susceptibility of C57BL was associated with a great number of microorganisms in the organs and with the corresponding histological changes. It was shown that the magnitude of the inflammation induced by Y. pseudotuberculosis varied among the host strains used. The variations of the susceptibility to Y. pseudotuberculosis among inbred mouse strains suggest the possible role of genetic factors regulating the host defence.

Experimental infection with Yersinia pseudotuberculosis of ground squirrels (Citellus citellus).

An experimental infection was induced in the European ground squirrel (Citellus citellus) by intraperitoneally injecting of 1 ml. of microbial suspension, containing 1 x 10(9) CFU (colony forming units) of Yersinia pseudotuberculosis, serotypes I and III. The infectious process was dynamically followed up from the 1st up to the 30th day, respectively. Account was rendered to the general condition, the internal body temperature and the mortality rate. The phagocytic activity of alveolar macrophages (aMa) and polymorphonuclear leucocytes (PMNL), isolated from the experimental animals, was also determined, as well as the degree of bacterial dissemination into the viscera and the histomorphological changes that found in the parenchymal organs. These investigations confirm the fact that the bacterial agent has a broad spectrum of alterations in the organism of the host--the European ground squirrel (Citellus citellus) in which the pseudotuberculosis develops as a generalized infection, especially pronounced in the animals that were infected with the serotype III.

Studies on aerosol Yersinia pseudotuberculosis infection of guinea-pigs.

Aerosol Y. pseudotuberculosis infection in guinea-pigs has been reproduced. In the course of infectious process, alveolar macrophages respiration is activated due to a rise in their cytochrome oxidase activity.