Enterobacteriaceae: Yersinia spp./Yersiniosis

Yersinia is a genus of bacteria characterized as gram-negative bacilli that are facultative anaerobic with bipolar staining. There are 2 enteropathogenic species that cause yersiniosis, Y. enterocolitica and Y. pseudotuberculosis. Infections are manifested as pseudoappendicitis or mesenteric lymphadenitis, and enterocolitis. The bacteria are transmitted through consumption of contaminated food products or water. Manifestations include fever, abdominal pain, and/or diarrhea. The gastrointestinal illness is usually self-limiting. Antibiotics are given for severe infection and in immunocompromised patients.

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Gram negative bacteria classification flowchart

Gram-negative bacteria:
Most bacteria can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thin layer of peptidoglycan do not retain the crystal violet stain utilized in Gram staining. These bacteria do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative. These bacteria can be further classified according to morphology (diplococci, curved rods, bacilli, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteria can be more narrowly identified by growing them on specific media (triple sugar iron (TSI) agar) where their enzymes can be identified (urease, oxidase) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain
** Pleomorphic rod/coccobacillus
*** Require special transport media

Image by Lecturio.

General Characteristics

Basic features of Yersinia spp.

  • Structure: bacilli/rods
  • Gram stain: gram negative 
  • Other stain(s): 
    • Stains such as Wright’s, Giemsa’s, and Wayson’s
    • Bipolar staining (retain staining at the ends of the cells) or “safety pin” appearance 
  • Spore formation: non-spore forming
  • Invasion and replication in relation to the host cell(s): facultative intracellular
  • Oxygen requirement: facultative anaerobes
  • Enzymes/biochemical tests:
    • Oxidase negative
    • Lactose negative

Clinically relevant species and diseases

Yersinia cause disease in animals; humans are usually incidental hosts. Three species are pathogenic to humans:

  • Enteropathogenic Yersinia causing yersiniosis (diarrheal illness):
    • Yersinia pseudotuberculosis (Y. pseudotuberculosis)
    • Y. enterocolitica
  • Y. pestis (not enteropathogenic but causes the plague; discussed separately)
3D computer generated image of Yersinia enterocolita

Three-dimensional (3D) computer-generated image of oblong-shaped Y. enterocolitica

Image: “3D computer generated image of Yersinia enterocolita” by Jennifer Oosthuizen. License: Public domain.


  • Yersiniosis: mostly due to Y. enterocolitica
  • Incidence generally highest among children
  • Diarrhea is often the presentation of infections affecting children < 4 years of age.

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Reservoir and transmission

  • Reservoir: livestock, rodents, domestic animals
  • Transmission:
    • From consumption of contaminated food or water (pork, milk, or milk products)
    • Blood products

Virulence factors

  • Lipopolysaccharide endotoxin: leads to systemic toxicity in bacteremia
  • Type III secretion system: 
    • Injects Yersinia outer membrane proteins (Yops) into the host cell
    • Yops trigger cytotoxic events and inhibit phagocytosis as well as biochemical pathways.
  • High-pathogenicity island (HPI): 
    • Encodes for an iron-scavenging siderophore, yersiniabactin
    • Yersiniabactin provides the bacterium the ability to take iron molecules needed for growth and dissemination.
  • Virulence regulation by temperature and calcium: 
    • Expression of Yersinia virulence factors is affected by temperature and free calcium. 
    • Physiologically, the mammalian host temperature is different from that of an insect.
    • Likewise, the calcium concentration is different intracellularly from extracellular fluids. 
    • Yersinia: able to adjust virulence factors based on the above actions, with the life cycle continuing in the environment or the host
  • Enteropathogenic Yersinia: has invasin, which binds to the surface of host cells 

Disease process

  • Organism in contaminated food enters the host and invades the M cells of the intestinal Peyer’s patches.
  • Invasion is facilitated by virulence factors.
  • Localizes and forms microabscesses in the intestinal lymphoid tissue and regional mesenteric lymph nodes
  • Gut infection → diarrhea (yersiniosis), abdominal pain, fever

Clinical Presentation


  • Most common in younger children 
  • Incubation: 3 days
  • Duration: 1–2 weeks
  • Signs and symptoms: 
    • Watery to bloody diarrhea
    • Fever
    • Nausea, vomiting
    • Pharyngitis can accompany the illness.
  • Course is longer than most forms of infectious diarrhea.
  • Septicemia can occur in:
    • Immunocompromised patients (e.g., patients with acquired immunodeficiency syndrome (AIDS))
    • Those with iron overload or hemochromatosis
    • Advanced age or infants
    • Liver disease
    • Malignancy
    • Diabetes


  • Also called acute mesenteric lymphadenitis
  • In older children and young adults
  • Signs and symptoms:
    • Vomiting, +/- mild diarrhea
    • Right lower quadrant abdominal pain
    • Fever, leukocytosis
    • In surgery, the appendix is usually normal but visible inflammation is noted around:
      • Terminal ileum
      • Mesenteric lymph nodes

Post-infectious sequelae

  • Occur in patients with HLA-B27 phenotype
  • Most common:
    • Erythema nodosum
    • Reactive arthritis (within 2–4 weeks of a preceding infection)

Transfusion-related septicemia

  • Y. enterocolitica in red blood cells of an asymptomatic donor
  • Organism can multiply to toxic levels in refrigerated blood.


Diagnostic tools

  • Specimen(s) that can be used:
    • Stool (preferred in gastrointestinal presentation)
    • Pharyngeal exudates
    • Peritoneal fluid or blood
    • Mesenteric lymph nodes/surgical specimen if surgical exploration is done
  • Smear and culture:
    • Bipolar staining (safety pin shape) in Wright’s, Giemsa’s, or Wayson’s stains 
    • Fluorescent antibody stains targeting the capsular F1 antigen
    • Specimen cultured in blood agar, MacConkey agar plates, and brain–heart infusion broth
    • Yersinia-specific culture medium: cefsulodin, irgasan, novobiocin (CIN) agar
  • Serology: antibody titer 1:16 or higher (in an unvaccinated patient)
  • Specific polymerase chain reaction (PCR)
Yersinia enterocolitica gram

Yersinia enterocolitica: a photomicrograph of a gram-stained culture revealing the presence of numerous gram-negative Y. enterocolitica bacteria

Image: “Yersinia enterocolitica gram” by the CDC. License: Public domain.



  • Diarrhea is usually self-limiting.
  • Fluid and electrolyte replacement
  • If needed in invasive infections or immunocompromised patients, antibiotic choices: 
    • Ciprofloxacin (preferred)
    • Trimethoprim-sulfamethoxazole
    • Doxycycline
  • Antibiotics for septicemia:
    • 3rd-generation cephalosporin (ceftriaxone) + gentamicin
    • Alternative: ciprofloxacin
  • Surgical exploration: acute mesenteric lymphadenitis versus appendicitis (if an acute abdomen could not be ruled out)


  • Sanitary precautions 
  • Avoid consumption of raw or undercooked meat. 
  • Routine treatment of municipal water
  • Testing of packed red blood cells for endotoxin (to reduce transfusion-associated septicemia)

Differential Diagnosis

  • Appendicitis: the acute inflammation of the vermiform appendix. Features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. The diagnosis can be established clinically and by imaging (computed tomography scan). The standard treatment is appendectomy.
  • Anthrax: an infection caused by Bacillus anthracis. Bloody diarrhea, abdominal pain, and vomiting are noted in gastrointestinal anthrax. Anthrax can also present as a cutaneous (blisters, ulcers with black eschar) and inhalational disease (dyspnea). History, PCR, and culture help with the diagnosis. Antimicrobial treatment and antitoxin are given for systemic anthrax.
  • Other infectious colitis: presents with acute onset fever and diarrhea. Other causative enteric pathogens include Salmonella, Campylobacter, E. coli (O157:H7), Shigella, and Clostridioides difficile, which can be confirmed with stool cultures and PCR. The course may be self-limiting or require antibiotic treatment.


  1. Bach, S., Buchreiser, C., Prentice, M., Guiyoule, A., Msadek, T., & Carniel, E. (1999). The High-Pathogenicity Island of Yersinia enterocolitica Ye8081 Undergoes Low-Frequency Deletion but Not Precise Excision, Suggesting Recent Stabilization in the Genome. Infect Immun. 67(10), 5091–5099.
  2. Prentice, M.B. (2018). Plague and other yersinia infections. In Jameson J, et al. (Ed.) Harrison’s Principles of Internal Medicine, 20th ed. McGraw-Hill.
  3. Riedel S, Hobden J.A., Miller S, et al. (Eds.) (2019). Yersinia and pasteurella. In Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28th ed. McGraw-Hill.
  4. Ryan, K.J. (Ed.). (2017). Enterobacteriaceae. In Sherris Medical Microbiology, 7th ed. McGraw-Hill. 
  5. Tauxe, R., Calderwood, S., Kaplan, S., & Bloom, A. (2019). Clinical manifestations and diagnosis of Yersinia infections. UpToDate. Retrieved Jan 6, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-yersinia-infections
  6. Tauxe, R., Calderwood, S., Kaplan, S., & Bloom, A. (2019). Treatment and prevention of Yersinia enterocolitica and Yersinia pseudotuberculosis infection. UpToDate. Retrieved Jan 6, 2021, from https://www.uptodate.com/contents/treatment-and-prevention-of-yersinia-enterocolitica-and-yersinia-pseudotuberculosis-infection
  7. Tauxe, R., Calderwood, S., & Bloom, A. (2019). Microbiology and pathogenesis of Yersinia infections. UpToDate. Retrieved Jan 6, 2021, from https://www.uptodate.com/contents/microbiology-and-pathogenesis-of-yersinia-infections

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