# Shiga Toxin-Producing E. coli (STEC): Infection, Pathogenesis, and Prevention

> What Is Shiga Toxin-Producing E. coli (STEC)? Shiga toxin-producing Escherichia coli (STEC) are the strains of E. coli which produce Shiga toxins (Stx)...

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Author: Sourav Pan
Last updated: September 16, 2026

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## What Is Shiga Toxin-Producing E. coli (STEC)?

Shiga toxin-producing Escherichia coli (STEC) are the strains of E. coli which produce Shiga toxins (Stx), either Shiga toxin 1 (Stx1), Shiga toxin 2 (Stx2), or both. Shiga toxin production is the main character of this group.

Not every E. coli is STEC. E. coli is a highly diverse bacterial species, with many strains normally living in the intestine without producing disease. Some are pathogenic. These strains possess particular virulence factors and may cause intestinal or extraintestinal infections. Among the diarrheagenic E. coli, the strains producing Shiga toxin are placed under STEC.

“STEC infection” has a more specific meaning than “E. coli infection”. It means an infection with Shiga toxin-producing E. coli. The term “E. coli infection” alone can also include infections caused by other pathogenic forms of E. coli, where Shiga toxin is not involved.

### STEC vs Harmless and Other Pathogenic E. coli

A large number of intestinal E. coli live as normal commensal bacteria. They usually do not carry the particular diarrheagenic virulence factors.

Pathogenic E. coli are different. Different strains possess different virulence properties and are grouped into [pathotypes](https://biologynotesonline.com/what-are-the-pathotypes-of-e-coli-etec-epec-ehec-eaec-eiec-daec/) according to these properties and the way they produce disease. In STEC, it is the Shiga toxin-producing ability.

E. coli groupMain characterRelation with STECNormal intestinal E. coliCommon commensal E. coli of the intestine. Usually without diarrheagenic virulence factorsNot STEC unless Shiga toxin genes are acquired and expressedOther diarrheagenic E. coliPathogenic strains having other characteristic virulence mechanismsDifferent diarrheagenic pathotypesSTECProduction of Shiga toxin (Stx1 and/or Stx2)Shiga toxin-producing diarrheagenic E. coli

The name STEC is based on toxin production, not merely on the detection of E. coli in a specimen. Shiga toxin genes (stx1 and stx2) or their toxin products can be detected for identification.

### O157 and Non-O157 STEC

E. coli O157 is one important STEC serotype. It is also the best-known one, being strongly associated with outbreaks of hemorrhagic colitis and severe human disease.

But STEC is not only O157.

Other serotypes produce Shiga toxin as well. These are commonly called non-O157 STEC. O26, O45, O103, O111, O121, and O145 are some of the better recognized non-O157 serogroups causing human illness, along with other STEC serogroups. The Shiga toxin genes can vary among them. O157 as well as non-O157 STEC may contain stx1, stx2, or a combination of the Shiga toxin genes.

“O157” indicates the antigenic serotype of the bacterium. “STEC” indicates its Shiga toxin-producing character.

### STEC, VTEC, and EHEC Terminology

STEC and VTEC are generally synonymous terms. VTEC means “verotoxin-producing” or “verocytotoxin-producing E. coli”. The name “verotoxin” came from the damaging activity of these toxins on cultured Vero cells. These toxins were later recognized as belonging to the Shiga toxin family. STEC and VTEC are hence commonly used for the same toxin-producing group.

EHEC (enterohemorrhagic E. coli) is used somewhat differently. In many publications, the term has been used for STEC associated with bloody diarrhea and hemolytic uremic syndrome (HUS), sometimes almost in the same sense as STEC.

In a stricter use, EHEC represents a subset of STEC with additional pathogenic characters. The ability to form attaching and effacing intestinal lesions, commonly associated with the locus of enterocyte effacement (LEE), is one such character. Use of “EHEC” is not completely uniform among different publications.

## Shiga Toxin Structure

Shiga toxin (Stx) is an AB5 toxin made up of one A subunit and five B subunits. The A part has the enzymatic activity, whereas the B portion is mainly for receptor binding.

![Shiga toxin AB5 structure showing the catalytic A1 region, A2 connector, five-membered B pentamer and B-subunit binding to Gb3 on a host membrane.](https://biologynotesonline.com/wp-content/uploads/2024/03/Structure-of-Shiga-Toxin-AB5-Complex-1024x768.webp)Shiga toxin AB5 structure showing the catalytic A1 region, A2 connector, five-membered B pentamer and B-subunit binding to Gb3 on a host membrane.

The structure of Shiga toxin includes-

- A subunit- It is a single subunit of about 32 kDa. This is the enzymatically active part of Shiga toxin and possesses RNA N-glycosidase activity.

- A1 fragment- After proteolytic cleavage, A subunit gives A1 and A2 portions. A1 is the larger catalytic portion containing the active site responsible for ribosome-inactivating activity.

- A2 peptide- A small portion of A subunit. It remains connected with A1 through a disulfide bond. A2 extends through the central opening of the B pentamer and connects the A part with B portion of toxin.

- B subunits- Five identical B subunits are present, each about 7.7 kDa. They associate together forming a ring-like pentamer. The B pentamer binds mainly with globotriaosylceramide (Gb3/CD77) receptor of susceptible cells.

- Arrangement of A and B subunits- The five B subunits form a central pore. The C-terminal A2 portion extends into this opening and the A subunit remains associated with the B pentamer by non-covalent interactions. The toxin structure is represented as A + B5.

- Stx1 and Stx2- Both have the same basic AB5 arrangement. Their amino-acid sequences are not identical and they are antigenically different. Most Shiga toxins recognize Gb3, while Stx2e preferentially binds with Gb4.

## Shiga Toxin Mechanism of Action

Shiga toxin (Stx) first binds with the susceptible host cell and enters inside the cell. After intracellular transport, the active A1 portion reaches the cytoplasm where it acts on the ribosome and stops protein synthesis.

![Shiga toxin binds Gb3, enters an endosome, moves retrogradely through the Golgi and ER, releases A1 into the cytosol and damages 28S rRNA to inhibit protein synthesis.](https://biologynotesonline.com/wp-content/uploads/2024/03/Shiga-Toxin-Mechanism-of-Action-and-Retrograde-Transport-1024x576.webp)Shiga toxin binds Gb3, enters an endosome, moves retrogradely through the Golgi and ER, releases A1 into the cytosol and damages 28S rRNA to inhibit protein synthesis.

The mechanism of action of Shiga toxin occurs in the following steps-

- Binding with host-cell receptor- The five B subunits of Shiga toxin bind mainly with globotriaosylceramide (Gb3/CD77) receptor present on the surface of susceptible host cells. This binding takes place before the entry of toxin into the cell.

- Endocytosis- After binding, the toxin along with its receptor is taken inside the host cell by endocytosis. The toxin-receptor complex then enters the endosomal compartment.

- Retrograde transport- From the endosome, Shiga toxin is transported towards the Golgi apparatus and from Golgi to the endoplasmic reticulum (ER). This backward movement of toxin through the intracellular compartments is referred to as “retrograde transport”.

- Cleavage of A subunit- During transport, the A subunit is cleaved by the host protease furin. Two portions are formed, A1 and A2. At this stage, both portions remain connected by a disulfide bond.

- Release of A1 fragment- In the ER, the disulfide bond joining A1 and A2 is reduced. The active A1 fragment gets separated. It is then transferred from the ER into the cytoplasm with the help of ER-associated transport machinery.

- Action on 28S rRNA- The A1 fragment acts as an RNA N-glycosidase. It removes a specific adenine residue from the α-sarcin/ricin loop of 28S rRNA present in the 60S ribosomal subunit.

- Inhibition of protein synthesis- The damaged ribosome is unable to perform normal protein synthesis. Interaction of elongation factors with the ribosome is disturbed. Translation stops.

- Other cellular effects- Ribosomal damage can also produce ribotoxic stress. ER stress and inflammatory signaling may occur. In susceptible cells, apoptosis can also develop.

## Sources and Reservoirs of STEC

Reservoirs are the animal hosts in which STEC is carried and maintained, while sources are the food, water, animals, or contaminated surroundings from which humans come in contact with the organism. The major reservoirs are cattle and other ruminants. Sources are different, and can change from one contamination event to another.

![STEC transmission pathways from cattle and other ruminant reservoirs through manure, meat, raw milk, produce, water and farm environments to human exposure and person-to-person spread.](https://biologynotesonline.com/wp-content/uploads/2024/03/Reservoirs-and-Sources-of-STEC-Infection-1024x576.webp)STEC transmission pathways from cattle and other ruminant reservoirs through manure, meat, raw milk, produce, water and farm environments to human exposure and person-to-person spread.

The important reservoirs and sources of STEC include-

- Cattle- The principal natural reservoir of STEC. The bacteria can remain in the intestinal tract of cattle without obvious disease and are passed out through feces. Beef as well as dairy cattle can carry them. Fecal shedding also brings STEC into manure, animal hides, soil, water, and farm surroundings.

- Sheep and goats- These animals are also recognized ruminant reservoirs. STEC may be carried in the intestine and shed with feces. Deer and some other wild or domesticated ruminants have also been found carrying the organism.

- Other animals and wildlife- Pigs, birds, rabbits, rodents, dogs, and different wildlife species have been found with STEC. Their reservoir importance is not the same as cattle. Some act as carriers or may take the organism from one contaminated environment to another.

- Beef and meat products- A source, not the natural reservoir. During slaughter and processing, STEC from feces or contaminated animal hides can get onto the carcass. In ground or minced beef, surface contamination may become mixed through the meat. Raw and insufficiently cooked beef, sausages, and other meat products have been involved in STEC infections.

- Raw milk and dairy products- Milk may pick up STEC during milking, particularly through fecal contamination or contaminated farm surroundings. Unpasteurized milk is a recognized source. Dairy products prepared or handled without an effective killing step can also carry the organism.

- Fresh vegetables and fruits- Not only foods of animal origin. Lettuce, spinach, sprouts, and other fresh produce may become contaminated from manure, soil, irrigation water, or runoff containing animal feces. Fruits are also involved. Unpasteurized fruit juices, including apple cider, have served as vehicles of STEC.

- Water- Surface water, wells, drinking-water sources, and recreational water may contain STEC after fecal contamination. Animal manure runoff and sewage are two routes by which it gets into water. Depending on environmental conditions, the organism can remain there for considerable periods.

- Animal contact and farm environment- Eating contaminated food is not necessary for every infection. Direct contact with cattle, sheep, goats, or their feces can expose a person to STEC. Farms and petting zoos are common settings where this type of exposure can occur. Animal bedding, soil, fences, and fecally contaminated surfaces can also become sources.

- Manure, soil, and contaminated environment- STEC shed from reservoir animals gets into manure and surrounding soil. From there, runoff or irrigation water can move the organism further and contaminate water or crops.

- Infected humans- Person-to-person spread occurs by the fecal-oral route. A person shedding STEC, with or without obvious symptoms, can act as an immediate source for another person. Humans are not the principal natural reservoir.

- Food-associated sources- There is no one universal “most common” food for STEC in every place and every outbreak. Ground beef and other beef products are well-recognized vehicles, but raw milk, dairy products, leafy vegetables, sprouts, fruits, unpasteurized juices, and contaminated water have also been involved. Which one becomes the source depends on where contamination has taken place.

## Virulence Factors of STEC

STEC contains different virulence factors which take part in bacterial attachment, colonization of intestine, injury of host cells, and development of severe disease. All these factors are not found equally in every STEC strain. Shiga toxin (Stx) is the major virulence factor.

The important virulence factors of STEC are-

- Shiga toxins (Stx)- Shiga toxin is the major virulence factor of STEC. Two principal forms are Stx1 and Stx2. Both are AB5 toxins, consisting of one A subunit and five B subunits. The five B subunits bind the toxin with its receptor, mainly globotriaosylceramide (Gb3). The A subunit damages the 28S rRNA of 60S ribosomal subunit, stopping protein synthesis. The stx genes are generally carried by [lysogenic bacteriophages](https://biologynotesonline.com/bacteriophages/). Among these toxins, Stx2, particularly Stx2a, has a stronger association with severe disease and hemolytic uremic syndrome (HUS).

- Locus of enterocyte effacement (LEE)- It is a large pathogenicity island found in many clinically important STEC. LEE carries the genes required for formation of characteristic “attaching and effacing” (A/E) lesion on the intestinal epithelial cells. Intimin, Tir, type III secretion system, and different secreted effector proteins are encoded by this region. LEE is absent in some STEC strains.

- Intimin- It is an outer membrane adhesin. Intimin is encoded by the eae gene and helps in close attachment of the bacterial cells with intestinal epithelial cells by binding to Tir. During this attachment, the underlying microvilli are lost and an A/E lesion is produced.

- Tir (translocated intimin receptor)- Tir is produced by the bacterial cell, but later transferred into the host cell. It gets inserted in the host-cell membrane. Here it acts as a receptor for intimin.

- [Type III secretion system (T3SS)](https://biologynotesonline.com/bacterial-secretion-systems-definition-types-mechanism-importance/)- It is a secretion apparatus through which bacterial proteins are delivered directly into the intestinal epithelial cells. Several proteins encoded in LEE take part in this system, including EspA, EspB, EspD, and other effectors. These injected proteins alter the functions of host cell and participate in formation of the A/E lesion.

- Enterohemolysin (EhxA)- Enterohemolysin is a plasmid-encoded hemolysin present in many STEC strains. It is encoded by the ehxA gene and belongs to the RTX toxin family. EhxA is also used as an additional virulence marker. Its exact role in human disease, however, is less clearly established in comparison to Shiga toxin.

- Additional adhesins- Several other adhesins can be used by STEC for attachment and colonization of the intestine. These include long polar fimbriae (Lpf), STEC autoagglutinating adhesin (Saa), Iha, Efa1, ToxB, and some other adhesins. Saa is particularly found in some eae-negative STEC, where attachment mediated by intimin is absent.

- EspP- It is an extracellular serine protease autotransporter encoded on the virulence plasmid of some STEC. EspP can cleave different host proteins, including coagulation factor V. It has also been associated with bacterial colonization and tissue effects. It is not present in every STEC strain.

- Subtilase cytotoxin (SubAB)- SubAB is another AB5 toxin, produced only by a subset of STEC. It occurs particularly among some LEE-negative strains. Its A subunit acts as a serine protease and cleaves the endoplasmic-reticulum chaperone BiP/GRP78. This produces disturbance in protein folding and severe ER stress.

- StcE and KatP- Some STEC strains also contain these plasmid-associated virulence factors. StcE is a zinc metalloprotease associated with bacterial adherence. KatP is a catalase-peroxidase which can protect against oxidative stress. Their distribution varies among different STEC strains.

## Pathogenesis of STEC Infection

The pathogenesis of STEC infection is a multistep process which begins after the entry of STEC into the gastrointestinal tract, followed by intestinal colonization and production of Shiga toxin (Stx).

The bacterial cells generally remain in the intestine. It is mainly the Shiga toxin which passes beyond the intestinal site and causes systemic damage.

![LEE-positive STEC attached to an intestinal epithelial cell through intimin and Tir, with type III secretion, microvillus effacement and actin-pedestal formation.](https://biologynotesonline.com/wp-content/uploads/2024/03/Attaching-and-Effacing-Lesion-Formation-by-LEE-Positive-STEC-819x1024.png)LEE-positive STEC attached to an intestinal epithelial cell through intimin and Tir, with type III secretion, microvillus effacement and actin-pedestal formation.

The steps involved in the pathogenesis of STEC infection are as follows-

### 1. Entry and Survival in the Gastrointestinal Tract

STEC enters the body through contaminated food, water, or by fecal-oral transmission.

After ingestion, the bacteria first pass through the acidic condition of the stomach. The surviving bacterial cells reach the intestine where they begin to compete with the normal intestinal microorganisms.

Colonization mainly occurs in the distal intestine and colon. STEC generally does not produce infection by deeply invading the intestinal tissue like some of the invasive enteric bacteria.

### 2. Initial Attachment to Intestinal Cells

The next step is the initial attachment of bacterial cells with the intestinal epithelium.

Different fimbriae, pili, and other adhesins can take part in this first contact. The exact attachment factors are not same in every STEC strain.

This initial attachment helps the bacterial cells to remain in the intestine rather than simply being removed along with the intestinal contents. It also supports colonization.

### 3. Intimate Attachment and A/E Lesion Formation

In LEE-positive STEC, initial attachment is followed by a more intimate attachment with the intestinal epithelial cells.

The locus of enterocyte effacement (LEE) carries genes for the type III secretion system (T3SS), intimin, Tir, and several effector proteins.

In this step, the T3SS transfers Tir (translocated intimin receptor) and other bacterial proteins into the intestinal epithelial cell. Tir becomes inserted into the host-cell membrane. Intimin present over the bacterial surface then binds with Tir.

A very close attachment between the bacterial cell and intestinal epithelial cell is formed.

The microvilli below the attached bacteria are lost. Actin is rearranged and a pedestal-like structure is produced. This is referred to as the “attaching and effacing” (A/E) lesion.

Some STEC are LEE-negative. These strains colonize by other adhesins without using this typical mechanism.

### 4. Intestinal Damage and Diarrhea

During this process, colonization and bacterial effector proteins disturb the normal intestinal epithelium.

Loss of microvilli occurs. Changes in the epithelial cytoskeleton, alteration of barrier function, and intestinal inflammatory responses are also produced.

Diarrhea develops during intestinal infection. In severe intestinal disease, mucosal injury is associated with hemorrhagic colitis and bloody diarrhea. Shiga toxin can also take part in the intestinal injury.

### 5. Production and Release of Shiga Toxin

The colonizing STEC produces Shiga toxin (Stx).

The toxin genes, stx1 and stx2, are generally carried by bacteriophages integrated within the STEC chromosome. Phage induction is closely associated with expression and release of Shiga toxin.

Stx is an AB5 toxin. Five B subunits take part in receptor binding, while the A subunit contains its enzymatic activity.

Stx2, particularly some Stx2 subtypes, has a stronger association with severe systemic disease and hemolytic uremic syndrome (HUS).

### 6. Passage of Stx Across the Intestinal Epithelium

The STEC bacterial cells mainly remain at the intestinal surface. Shiga toxin, however, can cross the intestinal barrier.

The exact mechanism by which this movement occurs in humans is not completely established. Stx produced within the intestinal lumen passes across the intestinal epithelium into the underlying tissue and finally reaches the circulation.

Transcellular transport and movement through a damaged or altered intestinal barrier have been described as possible routes.

### 7. Transport of Shiga Toxin to Target Organs

After entering the circulation, Shiga toxin is carried towards the susceptible tissues.

Its transport through human blood is complex and is still not completely understood. Interactions between Stx and blood cells have been described. Toxin-containing microvesicles can also be involved.

The kidney is one of the major target organs. In severe infection, other organs including the central nervous system may also be affected.

### 8. Binding and Entry of Stx into Target Cells

The B subunits of Shiga toxin bind mainly with globotriaosylceramide (Gb3/CD77) present on susceptible cells.

Gb3 is expressed in the human kidney, including cells of renal microvasculature and other renal cell types.

After receptor binding, Stx is taken inside the cell by endocytosis. The toxin is then transported backward through the intracellular compartments, from endosomes to Golgi apparatus and then to the endoplasmic reticulum (ER).

The active portion of the A subunit finally reaches the cytoplasm.

### 9. Inhibition of Protein Synthesis

Inside the cytoplasm, the enzymatically active A1 portion of Shiga toxin acts on the 28S rRNA of the 60S ribosomal subunit.

A specific adenine residue is removed from the rRNA. The affected ribosome becomes unable to function normally and protein synthesis is inhibited.

Stx can also produce ribotoxic stress, inflammatory signaling, and apoptosis in susceptible cells.

### 10. Endothelial Injury and Microvascular Thrombosis

Renal microvascular endothelial cells are important targets during severe STEC infection.

Shiga toxin causes injury and activation of endothelial cells. The affected vascular surface becomes more pro-inflammatory and prothrombotic.

Platelets become activated and are deposited within small vessels. von Willebrand factor (vWF), coagulation pathways, leukocytes, and inflammatory mediators also take part during this process.

Small platelet-rich thrombi are formed in the microvasculature. Complement activation may further take part in endothelial injury and thrombosis during STEC-HUS.

![STEC in the intestine releases Shiga toxin that reaches renal microvasculature, causes endothelial injury and microthrombi, and leads to hemolytic anemia, thrombocytopenia and acute kidney injury.](https://biologynotesonline.com/wp-content/uploads/2024/03/Pathogenesis-of-STEC-Associated-Hemolytic-Uremic-Syndrome-1024x576.webp)STEC in the intestine releases Shiga toxin that reaches renal microvasculature, causes endothelial injury and microthrombi, and leads to hemolytic anemia, thrombocytopenia and acute kidney injury.

### 11. Development of Hemolytic Uremic Syndrome (HUS)

When microvascular damage becomes severe, hemolytic uremic syndrome (HUS) can develop.

Red blood cells passing through the damaged and narrowed small vessels become mechanically fragmented. This produces microangiopathic hemolytic anemia.

Platelets are consumed during the formation of microthrombi, producing thrombocytopenia.

At the same time, injury and obstruction of the renal microvessels damage kidney function and can result in acute kidney injury.

## Symptoms and Disease Course

The symptoms of STEC infection mainly involve the gastrointestinal tract. Diarrhea and severe abdominal cramps are common. Vomiting may be present, while fever is usually absent or low. The disease may begin with watery diarrhea and later turns bloody in some cases.

The usual course can be represented as-

Exposure → Incubation period → Abdominal cramps and watery diarrhea → Bloody diarrhea in some cases → Recovery or development of complication

### Incubation Period and Symptom Onset

The symptoms do not appear immediately after exposure. There is an incubation period, usually around 3 to 4 days, although it may range from about 1 to 10 days.

After this period, abdominal cramps and diarrhea usually begin. The diarrhea is often watery or non-bloody at the beginning. Vomiting may also occur.

### Typical Gastrointestinal Symptoms

The following are the common symptoms of STEC infection-

- Diarrhea- Usually starts as watery diarrhea. It may be mild at first or becomes frequent during the illness.

- Abdominal cramps- Severe cramping abdominal pain is commonly seen with STEC infection. In some patients the pain can be quite strong.

- Vomiting- It is seen in some cases, but not in every patient.

- Fever- Fever is not a major feature. When present, it is usually low.

Loss of fluid from repeated diarrhea and vomiting may cause dehydration.

### Progression to Bloody Diarrhea

In some patients, the watery diarrhea later becomes bloody diarrhea. This may occur after about 1 to 3 days of the initial diarrhea. Severe abdominal cramps can continue during this period.

Bloody diarrhea is an important feature of the more severe intestinal disease, also referred to as hemorrhagic colitis. But it is not seen in every STEC infection. Some cases remain as non-bloody diarrhea.

A small number of patients may develop hemolytic uremic syndrome (HUS) several days after the diarrheal illness begins. In these cases, the disease course extends beyond the intestinal symptoms.

### Duration and Recovery

The gastrointestinal illness commonly lasts for about 5 to 7 days. Most uncomplicated infections improve within about one week.

Recovery is usually spontaneous. In patients who develop HUS or another severe complication, the illness continues beyond the usual diarrheal period and kidney involvement may occur.

## Hemolytic Uremic Syndrome (HUS)

Hemolytic uremic syndrome (HUS) is a severe complication of STEC infection characterized mainly by damage of small blood vessels, particularly the vessels of the kidney. It usually develops following the diarrheal illness.

HUS is mainly identified by three conditions, viz., microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI).

The important features of STEC-HUS are-

### How STEC Leads to HUS

- Shiga toxin activity- Shiga toxin produced by STEC in the intestine can reach the circulation. From here, it acts on susceptible vascular cells. The renal microvasculature is one of the important sites of its action.

- Microvascular injury- The toxin damages and activates the endothelial cells of small blood vessels. Small thrombi are formed within these affected vessels, where the platelets get trapped and are consumed.

- Hemolytic anemia- Red blood cells (RBCs) passing through these damaged small vessels are mechanically broken into fragments. This destruction of RBCs produces microangiopathic hemolytic anemia.

- Thrombocytopenia- It is the reduction in the number of circulating platelets. During HUS, platelets are used up in the formation of small-vessel thrombi.

- Acute kidney injury- Injury and obstruction of the renal microvasculature affect the normal functioning of the kidney. Urine production decreases. In severe conditions, kidney failure may occur.

### Signs and Clinical Features of HUS

HUS commonly develops several days after the beginning of diarrhea. In some cases, the intestinal symptoms may already begin to decrease when the signs of HUS start appearing.

Some of the important warning signs are-

- Reduced urination- The amount of urine becomes very low (oliguria). With severe kidney injury, urine production may stop.

- Pallor- The skin appears unusually pale because of continuous destruction of red blood cells and development of anemia.

- Fatigue and weakness- The affected person may become very tired or weak. Less activity than usual may also be observed.

- Bruising or petechiae- Reduction of platelets can lead to easy bruising. Small red or purple spots on the skin, referred to as petechiae, may also appear.

- Blood in urine- Blood in urine may be observed with renal involvement.

- Swelling and increased blood pressure- Decreased functioning of kidney can cause retention of fluid in the body. Swelling develops and blood pressure may increase.

- Neurological symptoms- Severe HUS can also affect the nervous system. Irritability, confusion, reduced alertness, seizures, or other neurological manifestations may occur.

Marked decrease in urination, unusual pallor, bruising, petechiae, severe weakness, or changes in alertness following STEC diarrhea require urgent medical evaluation. HUS is a medical emergency.

### Who Is at Greater Risk of Severe Disease

- Children younger than five years- Young children are particularly susceptible to the development of HUS following STEC infection.

- Older adults- Severe disease can also develop in older adults. The outcome may be more serious when HUS occurs.

- STEC producing Stx2- STEC strains carrying stx2, particularly stx2a, are more frequently associated with HUS compared to the Stx1-producing strains.

- Patients with vomiting and dehydration- Vomiting and dehydration occurring during the diarrheal stage have also been associated with an increased risk of progression to HUS.

### Outcomes and Supportive Management of HUS

There is no single supportive measure which is used for every patient with HUS. Management is based on the renal function, fluid condition, anemia, platelet count, electrolyte changes, and the presence of other complications. Hospital care is generally required.

- Fluid and electrolyte management- Fluid balance is maintained carefully according to the hydration condition and urine output of the patient. Electrolyte and acid-base abnormalities are corrected when required.

- Monitoring- Urine output and renal function are regularly monitored during the acute stage. Blood pressure, hemoglobin, platelet count, and electrolyte levels are also checked.

- Dialysis- Severe acute kidney injury may require dialysis. It is used according to the clinical requirement, such as severe loss of renal function, fluid overload, major electrolyte disturbances, or symptomatic uremia.

- Red blood cell transfusion- Packed red blood cell transfusion may be required when significant anemia develops.

- Platelet transfusion- A low platelet count alone does not routinely require platelet transfusion. It may be used under particular clinical conditions, including significant bleeding or when an invasive procedure is required.

## Diagnosis of STEC Infection

STEC infection is mainly diagnosed from stool specimens. Detection can be based on isolation of the organism, finding Shiga toxin (Stx), or detection of the toxin genes (stx1 and stx2). Culture, immunological methods and molecular tests are used for this purpose.

![STEC diagnostic workflow showing stool testing by O157 culture and Shiga toxin or stx gene assays, followed by public-health characterization, serotyping and genomic subtyping.](https://biologynotesonline.com/wp-content/uploads/2024/03/Laboratory-Diagnosis-of-STEC-Infection-819x1024.webp)STEC diagnostic workflow showing stool testing by O157 culture and Shiga toxin or stx gene assays, followed by public-health characterization, serotyping and genomic subtyping.

The important methods used for diagnosis are-

- Stool sample- Stool is the main clinical sample. It is better collected during the diarrheal stage and as early as possible, when STEC is still present in higher amount. A rectal swab may be used when stool sample is not available.

- Culture and isolation- Stool can be cultured for isolation of STEC. For E. coli O157, [sorbitol MacConkey agar (SMAC)](https://biologynotesonline.com/sorbitol-macconkey-agar-composition-preparation-and-uses/) is commonly used. Most O157 strains do not ferment sorbitol and therefore appear as non-sorbitol fermenting colonies. The suspected colonies are further identified by biochemical or serological tests. But this method alone is not sufficient. Many non-O157 STEC ferment sorbitol and will be missed by an O157-specific culture method.

- Detection of Shiga toxin- Shiga toxin present in stool or an enriched stool culture can be detected by enzyme immunoassay (EIA) and other immunological tests. Depending on the assay, Stx1 and Stx2 may also be differentiated. The sensitivity of toxin immunoassays is variable, particularly when unenriched stool is tested.

- PCR or other nucleic acid amplification tests (NAATs)- These tests detect the stx1 and stx2 genes. [Real-time PCR](https://biologynotesonline.com/real-time-pcr-qpcr-principle-protocol-application-advantages/) is widely used and can also be arranged as multiplex PCR for detection of several enteric pathogens from the same sample. Some assays detect additional genes such as eae, or targets for particular STEC serogroups. PCR gives high sensitivity for STEC detection and can detect non-O157 strains which are easily missed by O157-specific culture.

- Serotyping- Once STEC is isolated, its O and H antigens can be determined. O157 can be identified using O157-specific antisera, while other serogroups such as O26, O45, O103, O111, O121 and O145 can also be characterized with serological or molecular methods.

- Further strain characterization- PCR can be used for detection of virulence genes and Stx types or subtypes. [Whole genome sequencing (WGS)](https://biologynotesonline.com/whole-genome-sequencing/) is now also used in reference and surveillance laboratories for detailed characterization and comparison of STEC isolates, especially during outbreak investigation.

- When HUS is suspected- Stool testing for STEC is carried out along with blood and renal investigations. A complete blood count may show anemia and thrombocytopenia, while peripheral blood smear shows fragmented red blood cells (schistocytes). Serum creatinine is checked for renal injury.

- Late stool testing- STEC and its toxin can decrease rapidly from the intestine after the diarrheal illness. Hence, a negative stool test obtained later in a patient who has already developed HUS does not completely exclude an earlier STEC infection.

## Treatment and Clinical Management of STEC Infection

Treatment of STEC infection is mainly based on supportive care, replacement of the lost fluid and monitoring for the development of hemolytic uremic syndrome (HUS). No routinely established treatment is available that directly removes Shiga toxin.

The following are the important points for treatment and clinical management-

- Fluid and electrolyte replacement- In mild dehydration, oral rehydration is used. Intravenous isotonic fluid may be required when there is significant dehydration or the patient is unable to take enough fluid orally. Early correction of dehydration is important, especially in children.

- Monitoring for HUS- When severe disease is suspected, urine output, hemoglobin, platelet count, serum creatinine, electrolytes, and blood pressure are monitored. Reduced urine, pallor, bruising, edema, marked weakness, or neurological changes require further assessment.

- Antibiotics- Routine use of antibiotics is generally avoided in STEC infection, particularly with E. coli O157 and Stx2-producing STEC. It is also avoided when the toxin genotype is not known. Some antibiotics can increase the production or release of Shiga toxin. The effect is not same for every antibiotic, and selected drugs such as azithromycin are still being studied.

- Antimotility drugs- Drugs such as loperamide are avoided, especially during bloody diarrhea. These drugs reduce intestinal motility and may worsen the illness with increased risk of complications.

- Management of HUS- Hospital care is usually required for HUS. Fluid is adjusted according to urine output, renal function, body weight, ongoing losses, and edema. In patients having oliguria or anuria, excess fluid can be harmful.

- Dialysis- Hemodialysis or peritoneal dialysis may be required during severe acute kidney injury. Severe fluid overload, major electrolyte or acid-base disturbance, symptomatic uremia, or marked renal failure are some conditions where dialysis is used.

- Blood transfusion- Red blood cell transfusion may be needed when significant hemolytic anemia develops. Platelets are not routinely transfused only because the platelet count is low. In case of major bleeding or before some invasive procedures, platelet transfusion may be given.

- Other complications- Hypertension, seizures, electrolyte disturbances, and neurological problems are treated according to the clinical condition. Supportive care remains the main treatment during STEC-HUS.

- Follow-up- Renal function and blood pressure may need further monitoring after HUS. Persistent proteinuria, hypertension, or reduced kidney function can occur in some patients.

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