SHARED TRAITS

• Salmonella, Shigella, and Yersinia are members of the family Enterobacteriacea.
  – This family also includes Esherichia coli, Citrobacter, Serratia, Proteus, Klebisiella, and Morganella.
  – To learn more about their general properties and common virulence factors, please see our overview tutorial on E. coli.
• Salmonella, Shigella, and Yersinia gain access to the host by using Peyers’ patch M-cells to cross the intestinal epithelium.

SALMONELLA

• Be aware that Salmonella nomenclature is somewhat contested and highly confusing. Currently, the full name of an isolate includes italicized genus and species with non-italicized serovar type.
  – So, for example, the full name of the isolate that causes typhoid fever is: Salmonella enterica serovar Typhi; most authors shorten this to Salmonella Typhi.

• Salmonella causes foodborne infections.
• Does not ferment lactose, unlike the other members of Enterobacteriacea;
• Produces hydrogen sulfide.
• Infects both humans and non-human animals
  – Exception: Typhoid-causing strains are strict human pathogens.
• Intracellular pathogens that can invade all tissue types, including the brain.
• Virulence genes are encoded on Pathogenicity islands I and II:
  – Type three secretion systems inject effector proteins into host cells.
  – Salmonella-secreted invasion proteins, which facilitate entry into host cells.
  – Immune evasion proteins.
• Infection is acquired after consumption of contaminated foods, especially eggs, poultry, and dairy.

Salmonellosis

• Gastroenteritis, characterized by inflammation of the intestinal lining, is the most common form of Salmonellosis in the U.S.
  – Symptoms include nausea, vomiting, diarrhea, fever, and cramps.
  – Gastroenteritis is usually self-limiting, and requires only supportive care (i.e., water and ion replenishment).
  – Salmonella Typhimurium, the isolate often associated with gastroenteritis, resides in Salmonella-containing vacuoles (SCVs) within phagocytes; this protective endosome allows the bacteria to survive and replicated safely inside host cells.
• Septicemia causes typical bacteremia symptoms, including fever, chills, and low blood pressure.
  – In a small subset of patients, localized infections can develop, particularly in the joints and cardiovascular endothelium.
  – Salmonella septicemia is most common in young children and older adults, and in individuals with HIV or other immune deficiencies.
  – Be aware that recurrent septicemia is an AIDS-defining condition.
  – Treatment includes Fluoroquinolone or Cephalosporin antibiotics.

• Enteric fevers
• Typhoid fever is associated with Salmonella Typhi
• Paratyphoid fever, a milder form is associated with Salmonellaserotypes Paratyphi A, Paratyphi B, and Paratyphi C
  Be aware that S. Paratyphi B is also referred to as Salmonella Schottmeulleri, and S. Paratyphi C is also referred to as Salmonella Hirshfeldii
• Symptoms & Pathogenesis:
  – Approximately 10 days after ingestion of the bacteria, individuals experience fever, fatigue, and other non-specific symptoms; indicate that some patients develop “rose spots,” which are small red macules on the trunk.
  – Approximately 20 days after ingestion, patients experience gastrointestinal symptoms, which can include constipation or diarrhea, nausea, and vomiting.
  • We show that Typhoid-associated strains, such as SalmonellaTyphi, move through the lining of the intestine and are engulfed by macrophages.
    Macrophages carry the microbes to the bone marrow, liver, and spleen, where bacterial replication occurs.
    This sets the stage for bacteremia and the non-specific symptoms patients experience.
    Infection increases splenic cellularity and leads splenomegaly in some patients; liver enlargement has also been reported.
    Ultimately, the bacteria colonize the gallbladder and re-infect the intestines, producing gastrointestinal symptoms.
• Treatment includes administration of fluoroquinolones or ciprofloxacin.
• Write that asymptomatic carriers maintain typhoid-associated strains within populations; for example, enteric fever is endemic in Southeast Asia and parts of Africa.

SHIGELLA

• So closely related to Escherichia coli, particularly Enteroinvasive E. coli, that some authors call Shigella an E. coli biogroup.
• Shigella is an intercellular pathogen that only infects humans.
• Asymptomatic carriers are a key reservoir.
• Virulence factors are encoded on a plasmid, but regulated by chromosomal genes; this means that the plasmid, alone, is not enough to promote virulence.
  – Type three secretion systems inject effectors
  – Ipa’s A-D, facilitate invasion of epithelial cells and macrophages.
• Within host cells, Shigella lyses phagosomes and replicates within the cytoplasm; notice that this is unlike Salmonella, which replicates within special vacuoles.
• Actin tails facilitate Shigella migration to adjacent cells, which allows the bacteria to spread without exposure to agents of innate immunity.

Shigellosis

• Primarily affects small children; outbreaks are associated with daycares and preschools, and other places where fecal-oral transmission via contaminated hands is likely.
• Shigella has a low infectious dose.
• Upon infection, Shigella enterotoxin initially causes watery diarrhea.
• Then, as bacteria invade the colon mucosa, bloody diarrhea with pus, cramping, and fever occur.
  – The presence of neutrophils, red blood cells, and mucus in the stool is a helpful diagnostic criterion.
• Most patients with Shigellosis recover on their own; supportive care to prevent dehydration is all that is needed.
  – In severe cases, antibiotics can be administered.
• There are multiple pathogenic strains of Shigella:
  – Shigella sonnei is responsible for most cases of Shigellosis in the U.S.
  – Shigella flexneri is responsible for most cases of Shigellosis in developing countries.
  – Shigella dysenteriae causes dysentery, the most severe form of Shigellosis.
  These strains produce Shiga exotoxin, which impairs protein synthesis.
  As a result, damaged intestinal epithelium produces bloody diarrhea.
  Damaged renal endothelial cells can lead to Hemolytic uremia syndrome (HUS); this occurs most often in infected children.

YERSINIA

• Zoonotic infections.
• Short rods, aka, coccobacilli
• Bipolar Gram-staining: their tips stain darker than their middles.
• Type three secretion systems secrete immune-suppressingeffectors into host cells, which allows Yersinia to survive and replicate.

Plague

• Yersinia Pestis causes plague.
• Infected fleas and lice transmit the bacteria to humans.
• Virulence factors and their genes:
  – Antiphagocytic protein capsule (Factor 1 gene).
  – Outer membrane proteins degrade complement proteins C3b and C5a; this prevents bacterial opsonization and phagocyte migration (Plasminogen activator gene).
  – **Plasminogen activator proteases **also degrade fibrin clots, which may facilitate bacterial spread in the host (Plasminogen activator gene).
• Bubonic plague is characterized by fever, headache, chills, and weakness; replication in the lymph nodes produces swelling and tenderness – “buboes” refers to the visible lymph node swellings that typically appear in the axilla or groin.
• Septicemic plague occurs when infection spreads throughout the body via the bloodstream or lymph; it produces fever, chills, and extreme weakness, as well as abdominal pain, and, possibly, shock or bleeding into the skin or other organs.
• Pneumonic plague can quickly lead to respiratory failure and death; and, because is spread in respiratory droplets, transmission is human–to-human.
• Treatment includes streptomycin or gentamycin; because disease progression is rapid, and infection can spread to the lungs, early administration of these antibiotics is crucial.

Yersiniosis

• Yersinia enterocolitica and Yersinia pseudotuberculosiscause enterocolitis, especially in children.
• They are associated with *undercooked pork.
• Young children tend to experience bloody diarrhea, cramps, and fever.
• Older children tend to experience fever, and a pain in the right side of the abdomen that may be confused with appendicitis.
• In most cases, supportive care is sufficient.