YERSINIA DISEASES(Y. pseudotuberculosisand Y. enterocolitica)
Enteropathogenic species of Yersinia produce diseases associated with the gas- trointestinal tract, ranging from simple gastroenteritis with diarrhea and vomiting to syndromes in which the primary features are abdominal pain and fever. Yersinia mesenteric adenitis can simulate acute appendicitis. Y.enterocolitica is one of the causes of the enteric fever syndrome.
In animals, Y. pseudotuberculosis causes pseudotuberculosis, a disease characterized by lesions ranging from local necrosis to granulomatous inflammation in the lymph nodes, spleen, and liver. The portal of entry for humans is the gastrointestinal tract, presumably by consumption of contaminated food or water. In most cases animals, including wild an-imals, are the most likely source of infection, but the exact mode of transmission is un-known. Geographic variation in the frequency of Y.enterocoliticainfections is marked. The highest rates have been reported from some Scandinavian and other European coun-tries, with much lower rates in the United Kingdom and the United States. Low isolation rates may be partially attributable to the difficulty of growing Y.enterocolitica from stool specimens.
Enteropathogenic Yersinia entering the human host in contaminated food invade the M cells of the Peyer’s patch. The invasive process and its effect on the host cell are driven by a large array of virulence factors that are deployed under complex genetic and environ-mental regulation. These proteins include invasin, which binds to integrins on the surface of host cells, and the Yersiniaoutermembraneproteins(Yops), which are the major ef-fector proteins. The Yops are part of yet another contact secretion system that is deployed between the bacterial cell and host cell cytoplasm. When the Yops are injected into the host cell, they trigger cytotoxic events, including disruption of biochemical pathways (de-phosphorylation, serine kinase), sensor functions, and the actin cytoskeleton.
Some of the virulence factors produced by Yersinia are regulated in a system in which expression responds to either temperature or free calcium (Ca2+) concentration. The phys-iologic temperature in a mammalian host is different from that in an insect or the environ-ment, and the intracellular calcium concentration is markedly different from that of extra-cellular fluids. By sensing the environment, Yersinia is able to express or suppress virulence factors at different stages of the pathogenic process. The results seem timed to support the pathogenic strategy of Yersinia, which is to paralyze the phagocytic activity of defending macrophages and neutrophils and to nullify the host cellular immune response. The virulence determinants are encoded both on the bacterial chromosome and on a plas-mid that contains genes for the secretion apparatus and the Yops. Another genetic compo-nent is a PAI, which is found only in the three pathogenic species and not the other Yersinia.Theonly known component of this PAIis aniron scavengingsiderophore(yersiniabactin).
The biological outcome of this extraordinary multifactorial process is the enhanced capacity of the pathogenic Yersinia to enter and replicate within the RES and to delay the cellular immune response. This leads to the formation of microabscesses and destruction of the cytoarchitecture of Peyer’s patches and the mesenteric lymph nodes. The systemic symptoms seen with dissemination can largely be attributed to the effects of endotoxin.
Y. pestis is a specialized variant closelyrelatedto Y. pseudotuberculosis.Insteadofen-tering the intestinal tract Y. pestis reaches the dermal lymphatics by the bite of an infected flea. It has it own adhesin similar to that of invasin and two plasmids not found in the en-teropathogenic Yersinia. Unique virulence factors for Y. pestis include a capsular protein antigen with antiphagocytic properties, a plasminogen activator protease that promotes ad-herence to basement membranes, and a fibrinolysin that may play a survival role in the flea.