Yersinia pseudotuberculosis infection

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University of Oklahoma Study Abroad Microbiology in Arezzo, Italy[1]

Image of Yersinia psuedotuberculosis. From: tufts.edu [2]

Etiology/Bacteriology

Taxonomy

| Domain = Bacteria
| Phylum = Proteobacteria
| Class = Gamma Proteobacteria
| Order = Enterobacteriales
| Family = Enterobacteriaceae
| Genus = Yersinia
| species = Pseudotuberculosis

[1]

Description

Yersinia pseudotuberculosis is a pathogenic, Gram-negative microorganism with the capability to transmit between both humans and animals [2]. Reported human cases of Y. pseudotuberculosis have shown to stem from food and water contamination. However, cases of Y. pseudotuberculosis in humans are rare due to it being a primarily zoonotic infection. This organism possesses high virulence due to the secretion of the superantigenic exotocin YPM. Abdominal pain and fever accompany this infection. However, symptoms are not limited to these; there is a vast spectrum of symptoms that may arise from infection from these bacteria. Despite the large number of complications that may arise from Y. pseudotuberculosis, there is a low fatality rate. Diagnosis occurs through analysis of fecal samples, and Y. pseudotuberculosis may be isolated via MacConkey agar. To avoid infection caused by Y. pseudotuberculosis, one should avoid ingesting improperly cooked meat, unpasteurized milk and contaminated water. In addition, proper hand washing techniques can decrease exposure.

Pathogenesis

Transmission

Although Y. pseudotuberculosis is primarily a zoonotic disease, food-borne infections have been reported. Infection in humans occurs after the introduction of contaminated food products into the gastrointestinal tract. Water-borne infection has also been reported in Czechoslovakia, as well as, Okayama, Japan. [3] Y. pseudotuberculosis can be hosted in a number of different animal reservoirs such as: dogs, cats, cattle, horses, rabbits, deer, turkey, ducks and many others.

Infectious Dose and Incubation Period

Characteristic of other Yersinia infections, Yersinia pseudotuberculosis requires a dose of 10⁹ organisms to cause disease. The incubation period of Y. pseudotuberculosis is 5-10 days; however, durations of 2-20 days have been reported in occasional outbreaks with the average time being 4 days after exposure to the bacterium.

Epidemiology

According to the FDA, to date there have been no reported cases of Y. pseudotuberculosis due to food contamination in the United States. Sporadic outbreaks of the disease have been reported in Northern Europe and Japan [4]. In April of 2004, several cases of gastroenteritis, due to Y. pseudotuberculosis infection, were reported in school children in Finland. [5] Contaminated carrots were eventually implicated as the cause of infection. Many other documented cases are due to the consumption of unclean drinking water or contaminated water wells [3] . Most cases of Y. pseudotuberculosis are often sporadic and uncommon in humans, as it often causes disease in the animal host. Y. pseudotuberculosis has a low fatality rate in humans unless the patient presents with chronic liver disease. In this case, the mortality rate can exceed 75% [3] . Y. pseudotuberculosis does not appear to have any racial specificities but it is 3 times more common in men than women.

Virulence Factors

Yersinia pseudotuberculosis has a number of virulence factors that contribute to the pathogenicity of the organism.

Yops

Y. pseudotuberculosis contains a 70-kd plasmid that encodes for a type III secretion system that delivers the Yersinia outer proteins (Yops). There are four major Yops proteins which are essential to the pathogenicity of Y. pseudotuberculosis: YopE, YopJ, YopT, and YopH. YopE activates the RhoGTPase of the GTP-binding protein, which plays a role in the actin filament arrangement, promotion of cell rounding, prevention of host cell membrane pores, and inhibition of phagocytosis [3] . YopE also plays a role in decreasing the host cells proinflammatory signals by decreasing the production of interleukin-8. YopJ binds to the protein kinases which blocks phosphorylation in the cell. This will eventually lead to a decrease in the production of interleukin-8, affecting the host cells proinflammatory response. YopT disrupts the actin filament arrangement and prevents phacytosis by the host cell. YopT is not present in the pathogenic strains of Y. pseudotuberculosis. YopH contributes to the disruption of phagocytosis and actin filament arrangement. It also has a role in decreasing the secretion of interleukin-8. The four main Yersinia outer proteins work together to disrupt the host immune response.

Exotoxin-YPM

Some strains of Y. Pseudotuberculosis secrete the superantigenic exotoxin YPM, or Y. pseudotuberculosis-derived mitogen. YPM preferably stimulates the proliferation of CD4 T cells but some expression of CD8 does occur. Along with proliferation, YPM stimulates the overproduction of interleukin-8 increasing the inflammatory response in the host.

Adhesion Molecules

The adhesion molecules of Y. pseudotuberculosis bind to the host cell and facilitate its colonization in the host organism. The two major proteins of this group include: invasin and yadA. The invasin binds to the integrins of the M cells of Peyer’s patch in the small intestine. It also plays a role in internalization of bacteria across the M cells. YadA binds to laminin, collage, and fibronectin, which are bound to their receptors on the cell surface.

High Pathogenicity Island (HPI)

High Pathogenicity Island contains the gene that encodes yersiniabactin, which is used for iron uptake.

Twin Arginine Translocation (tat) pathway

The twin arginine translocation pathway is important for the secretion of proteins that function in motility and acid resistance.

Clinical Features

The two most common symptoms associated with Yersinia pseudotuberculosis infections are abdominal pain and fever. There is no staging process associated with Y. pseudotuberculosis infections. The abdominal pain is rather common, but the site of location can vary depending on where the bacterium targets the host. A number of clinical problems can manifest from Y. pseudotuberculosis including complications in the kidneys, gastrointestinal tract, and severe skin rashes. Systemic findings include fever, skin rash, strawberry tongue, and lymphadenopathy. The most common form of Y. pseudotuberculosis infection originates from the ingestion of contaminated foods, especially fresh produce. The ingestion of contaminated food or water, for example, has been shown to cause gastroenteritis, mesenteric lymphadenitis (reference below) and even erythema nodosum. Diarrhea is uncommon and additional systemic symptoms accompany people who develop Izumi fever. Although infections caused by Y. pseudotuberculosis are broad, the infections are usually self-limited with a low case-fatality rate. [6]

Diagnosis

Yersinia pseudotuberculosis has the potential to be difficult to culture because of the vast presence of healthy microbiota. A fecal sample is needed from the patient and then the microorganism can be isolated. Research has shown that cold-temperature enrichment has been effectively used to culture and isolate the microorganism. [7] Polymerase Chain Reaction assay can then be used to identify the bacteria and then can further serotype the organism. [8] The culture can also be isolated and grown on MacConkey agar due to its ability to ferment sorbitol and its ability to produce ornithine decarboxylase. [9] Y. pseudotuberculosis has been serotyped using Enzyme-linked immunosorbent assay along with agglutination tests but the results prove inconclusive due to the possibility of cross-reactions of other pathogenic antibodies. [9] Blood samples can be taken and tested to confirm the presence of the microorganism but a fecal sample is the preferred method of diagnostic testing. [8]

Treatment

The severity of the infection directly determines the level of treatment that is necessary to clear the colonization of Yersinia pseudotuberculosis. Many cases of Y. pseudotuberculosis are simply watched closely by a physician but action is never necessary due to the self-limiting nature of the bacteria. [9] If necessary, Y. pseudotuberculosis is susceptible to ampicillin, cephalosporins, aminoglycosides, tetracyclines, and chloramphenicol. [10 If the patient has underlying factors, such as immunodeficiency or severe dehydration, hospitalization may be required so that the correct level of treatment can be administered. [9]

Prevention

Food-borne and water-borne epidemics of Y. pseudotuberculosis can occur. Avoid ingesting uncooked meat, unpasteurized milk, and be aware of the possibilities of contaminated water. Caution should be taken when handling pork intestines especially. Proper hand washing methods should be put in place if ever handling pork in this manner. [3]

Host Immune Response

Y. pseudotuberculosis displays unique responses to the host immune system; it is characterized by virulence factors that enable the microorganism to sustain life within the host. One characteristic common to all Yersenia species is the ability to attack phagocytic cells, a crucial part of the host response to pathogenic invasions [11]. Despite its extracellular residence during pathogenesis, studies have shown that the host’s immune response compensates for the attack on phagocytic cells with CD8+ T cells [11]. The T cell effector molecule perforin plays an equally important role in the death and phagocytosis of the pathogen [11]. Cell death is characterized by apoptosis of naïve cells and pyroptosis of activated macrophages, which are non-inflammatory and inflammatory, respectively [12]. Y. pseudotuberculosis is most common in animals, but commonly affects children and immune-compromised individuals when it is transmitted [13].

Reference

1. http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi

2. Long, C., T.F. Jones., D.J. Vugia, J. Scheftel, N. Strockbine, P. Ryan, B. Shiferaw, R.V. Tauxe, L.H. Gould. Yersinia pseudotuberculosis and Y. enterocolitica Infections, FoodNet, 1996–2007. 2010. NCBI. 16(3): 566. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322025/#__ffn_sectitle>

3. Asim, J. A. "Pseudotuberculosis (Yersinia)". <http://emedicine.medscape.com/article/226871-overview#a0101>

4. http://www.fda.gov/Food/FoodborneIllnessContaminants/CausesOfIllnessBadBugBook/ucm070040.htm

5. "Yersinia pseudotuberculosis O:1 Traced to Raw Carrots, Finland." Emerging Infectious Diseases. Vol. 14, No 12, December 2008. <http://wwwnc.cdc.gov/eid/article/14/12/pdfs/08-0284.pdf>

6. Long C, Jones T, Gould L, et al. Yersinia pseudotuberculosis and Y. enterocolitica infections, FoodNet, 1996-2007. Emerging Infectious Diseases [serial online]. March 2010;16(3):566-567. Available from: MEDLINE, Ipswich, MA.

7. Abdulla, Z.A. and Kanan, T.A. "Isolation of Yersinia spp. from cases of diarrhoea in Iraqi infants and children". EMHJ - Eastern Mediterranean Health Journal, 15 (2), 276-284, 2009. <http://apps.who.int/iris/handle/10665/117636#sthash.I4SfU0C4.dpuf>

8. Nakajima, H.; Inoue, M.; Mori, T.; Itoh, K.; Arakawa, E. and Watanabe, H. "Detection and Identification of Yersinia pseudotuberculosis and Pathogenic Yersinia enterocolitica by an Improved Polymerase Chain Reaction Method". Journal of Clinical Microbiology Vol. 30, No.9. September 1992. <http://jcm.asm.org/content/30/9/2484.full.pdf>

9. Jani, A. and Chen, P. "Pseudotuberculosis (Yersinia) Workup". Medscape. November 2013. <http://emedicine.medscape.com/article/226871-workup#a0719>

10. "Yersinia pseudotuberculosis". The Public Health Agency of Canada. 2011. <http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/yersinia-pseudotuberculosis-eng.php#footnote4>

11. Bergman, M.A., W.P. Loomis, J. Mecsas, M.N. Starnbach, and R.R. Isberg. CD8+ T Cells Restrict Yersinia pseudotuberculosis Infection: Bypass of Anti-Phagocytosis by Targeting Antigen-Presenting Cells. 2009. NCBI. 5(9). <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731216/>

12. Bergsbaken, T., and B.T. Cookson. Innate immune response during Yersinia infection: critical modulation of cell death mechanisms through phagocyte activation. 2009. NCBI. 86(5). <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774879/>

13. Han, T.H., I.K. Pak, and S.J. Kim. Molecular Relatedness between Isolates Yersinia pseudotuberculosis from a Patient and an Isolate from Mountain Spring Water. 2002. NCBI. 18: 425. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055051/>

Created by Lindsey Baldwin, Tara Carlisle, Rachel Garrison, and Tory Kappel, students of Dr. Tyrrell Conway at the University of Oklahoma Italian Center