What is Enteroinvasive E. coli (EIEC)?

Enteroinvasive Escherichia coli (EIEC) is a pathogenic bacteria that shares similarities with Shigella, a bacteria known to cause shigellosis. EIEC infections lead to a syndrome that closely resembles shigellosis, characterized by severe diarrhea and high fever. Unlike other types of E. coli, EIEC is highly invasive and enters intestinal cells by utilizing adhesin proteins.

EIEC does not produce toxins but instead causes damage to the intestinal wall through mechanical destruction of cells. The bacteria possess a large virulence plasmid called pINV, which is also found in Shigella. This plasmid contributes to the similar disease phenotype observed in both EIEC and Shigella. EIEC strains have also lost the ability to synthesize cadaverine, produce the OmpT protein, and form curli, which are features shared with Shigella. However, it is worth noting that the term “EIEC” does not represent a monophyletic group within E. coli.

Once inside the host’s body, EIEC penetrates the epithelial wall and multiplies within the host cells, utilizing the host’s cellular machinery. The bacteria can extend to adjacent epithelial cells. EIEC strains carry genes for a type III secretion system, which acts as a virulence factor. Although the infection is invasive, it typically remains confined to the submucosal layer. The invasion of cells by EIEC can lead to a mild form of diarrhea or dysentery, often mistaken for Shigella-induced dysentery. The characteristic symptoms include blood and mucus in the stools, a condition known as colitis.

Ingesting contaminated food is the primary route of EIEC infection, with symptoms typically appearing within 12 to 72 hours. The illness is characterized by abdominal cramps, diarrhea, vomiting, fever, chills, and general discomfort. Fortunately, dysentery caused by EIEC is usually self-limiting and does not result in known complications.

The specific foods that may harbor EIEC are currently unknown, but any food contaminated with human feces from an infected individual, either directly or through contaminated water, can cause the disease in others. Outbreaks have been associated with hamburger meat and unpasteurized milk.

EIEC falls within the broader category of enterovirulent E. coli (EEC) group, which includes various types:

1. Enteroinvasive E. coli (EIEC): Invades the intestinal wall, leading to severe diarrhea.
2. Enterohemorrhagic E. coli (EHEC): Notable for E. coli O157:H7, it causes bloody diarrhea and hemolytic uremic syndrome (anemia and kidney failure).
3. Enterotoxigenic E. coli (ETEC): Produces a toxin that affects the intestinal lining, commonly associated with traveler’s diarrhea.
4. Enteropathogenic E. coli (EPEC): Can cause diarrhea outbreaks in newborn nurseries.
5. Enteroaggregative E. coli (EAggEC): Can cause acute and chronic diarrhea, particularly in children.

In summary, Enteroinvasive E. coli (EIEC) is a pathogenic bacterium that closely resembles Shigella and causes a syndrome similar to shigellosis. It invades the intestinal wall, resulting in severe diarrhea. While sharing similarities with other enterovirulent E. coli strains, EIEC is distinct in its invasive behavior and lack of toxin production. Proper food hygiene practices are important in preventing EIEC infections.

Infections by Enteroinvasive E. coli (EIEC)

• Disease caused by Enteroinvasive Escherichia coli (EIEC) is characterized by the ulceration of the bowel and the development of dysentery, a condition marked by diarrhea accompanied by mucus and blood. The symptoms are reminiscent of bacillary dysentery, which is caused by Shigella bacteria.
• EIEC’s invasive nature allows it to penetrate the intestinal wall, leading to the destruction of cells and subsequent ulceration. This damage to the bowel lining contributes to the characteristic symptoms of dysentery, including frequent bowel movements with the presence of mucus and blood.
• The resemblance between EIEC-induced dysentery and Shigella-induced dysentery is not surprising, considering the close relationship between EIEC and Shigella bacteria. EIEC shares similar virulence factors and disease mechanisms with Shigella, including the ability to invade intestinal cells and cause severe inflammation in the bowel.
• The presence of mucus and blood in the stool is a result of the damage inflicted on the intestinal wall by EIEC. The invasion of the bacteria triggers an inflammatory response, leading to the release of inflammatory mediators and the recruitment of immune cells to the affected area. This immune response contributes to the ulceration of the bowel and the shedding of mucus and blood into the stool.
• The clinical presentation of EIEC-induced dysentery typically includes symptoms such as abdominal pain, cramping, frequent and urgent bowel movements, and the passage of stools with mucus and blood. Fever and malaise may also accompany the gastrointestinal symptoms.
• It is important to differentiate EIEC-induced dysentery from other causes of diarrhea and dysentery, as the appropriate treatment and management strategies may vary. Proper diagnosis through laboratory testing, including stool culture and identification of the bacteria, is necessary to confirm the presence of EIEC.

Enteroinvasive E. coli (EIEC) Transmission

• The mode of transmission of Enteroinvasive Escherichia coli (EIEC) primarily involves food and water, although person-to-person transmission can also occur.
• EIEC outbreaks are commonly associated with the consumption of contaminated food or water. Foods that have been exposed to human feces, either directly or indirectly through contaminated water sources, can harbor EIEC and serve as a vehicle for transmission. Contaminated food items may include undercooked or raw meat, unpasteurized dairy products, fruits, vegetables, and other food products that have come into contact with contaminated water during production, processing, or handling.
• Waterborne transmission occurs when individuals ingest water contaminated with EIEC. This can happen when water sources are contaminated with fecal matter containing the bacteria. Inadequate treatment or improper sanitation practices can contribute to the presence of EIEC in water supplies, increasing the risk of infection.
• Person-to-person transmission of EIEC is possible but less common compared to other bacteria, such as Shigella species. The infective dose of EIEC required to cause infection in individuals is higher than that for Shigella, which means a larger number of bacteria is needed for transmission. This higher threshold reduces the likelihood of efficient person-to-person transmission. However, direct contact with infected individuals or with surfaces and objects contaminated by their feces can lead to the transfer of EIEC and subsequent infection.
• Proper hygiene practices play a crucial role in preventing the transmission of EIEC. Practicing good hand hygiene, especially after using the bathroom and before handling food, can help reduce the risk of contamination. Thoroughly cooking food, particularly meat products, and ensuring the consumption of safe drinking water are important preventive measures. Additionally, maintaining proper sanitation and hygiene standards in food production and processing facilities, as well as implementing appropriate water treatment and sanitation practices, are essential in minimizing the risk of EIEC transmission.
• In summary, Enteroinvasive Escherichia coli (EIEC) is primarily transmitted through the consumption of contaminated food and water. While person-to-person transmission can occur, the higher infective dose required for EIEC compared to Shigella reduces the likelihood of efficient transmission between individuals. Adhering to good hygiene practices, practicing proper food safety measures, and ensuring safe water sources are important in preventing the transmission of EIEC.

Enteroinvasive E. coli (EIEC) Pathogenesis

The pathogenesis of Enteroinvasive Escherichia coli (EIEC) involves several steps that contribute to its invasive nature and the resulting damage to the colonic epithelium.

1. Epithelial cell penetration: EIEC bacteria have the ability to penetrate the epithelial cells lining the colon. They use adhesin proteins to bind to and enter the cells, allowing them to establish an infection.
2. Lysis of the endocytic vacuole: After entering the epithelial cells, EIEC bacteria lyse the endocytic vacuole, which is the compartment where they are initially enclosed. This allows the bacteria to escape into the cytoplasm of the host cell.
3. Intracellular multiplication: Once inside the cytoplasm, EIEC bacteria exploit the host cell’s machinery to multiply and replicate. They utilize the resources and nutrients available within the host cell to support their growth and proliferation.
4. Directional movement through the cytoplasm: EIEC bacteria can move within the cytoplasm of the infected host cell. This movement is facilitated by the formation of actin tails, similar to what is observed in other intracellular pathogens like Listeria. The actin tails enable the bacteria to propel themselves and traverse through the host cell’s cytoplasm.
5. Extension into adjacent epithelial cells: EIEC bacteria can extend their infection by moving from one infected epithelial cell to adjacent cells. This allows them to spread throughout the colonic epithelium, contributing to the dissemination and severity of the infection.

It is important to note that EIEC is not toxigenic, meaning it does not produce toxins like some other pathogenic bacteria. Instead, its pathogenicity lies in its invasive nature and the ability to cause damage to the colonic epithelium.

The process of bacterial invasion into the colonic epithelium is mediated by a series of genes located on a plasmid, known as pInv genes. These genes play a crucial role in facilitating the invasion of EIEC into the epithelial cells. One key component involved in epithelial cell invasion is a plasmid-coded antigen called virulence marker antigen (VMA).

The destructive nature of EIEC infection can lead to colonic ulceration. As the bacteria multiply within the host cells and spread through the colonic epithelium, they cause the destruction of the infected cells. This process triggers an inflammatory response, resulting in the infiltration of immune cells and further contributing to the damage and ulceration of the colon.

In summary, the pathogenesis of Enteroinvasive Escherichia coli (EIEC) involves the penetration of epithelial cells, lysis of the endocytic vacuole, intracellular multiplication, directional movement through the cytoplasm, and extension into adjacent epithelial cells. The invasion into host cells is mediated by a set of genes on a plasmid, and the bacteria’s ability to destroy epithelial cells and induce inflammation can lead to colonic ulceration. EIEC is not toxigenic but relies on its invasive properties to cause disease.

Symptoms of Enteroinvasive E. coli (EIEC)

The clinical features of an infection caused by Enteroinvasive Escherichia coli (EIEC) are characterized by two main presentations: an initial stage of watery diarrhea followed by a dysenteric form of the disease.

1. Watery diarrhea: In the early stages of the infection, individuals may experience watery diarrhea. This type of diarrhea is characterized by loose, liquid stools without the presence of blood or mucus. The frequency of bowel movements may increase, leading to a greater volume of stool being passed.
2. Dysenteric form of the disease: In a subset of patients, the infection progresses to a dysenteric form of the disease. This stage is marked by the following clinical features:

• Fever: The presence of an elevated body temperature, often accompanied by chills, is a common symptom of EIEC infection.
• Malaise: Individuals may experience a general feeling of discomfort, fatigue, or unease.
• Abdominal cramps: Severe, crampy abdominal pain is a characteristic symptom of EIEC infection. The pain may be localized or spread throughout the abdominal area.
• Blood and leukocytes in stool specimens: As the infection progresses, there is a noticeable change in the appearance of the stool. Stool samples may contain visible blood, giving it a red or maroon color, as well as leukocytes (white blood cells), which are detected through laboratory analysis. The presence of blood and leukocytes in the stool is a hallmark of dysentery.

It’s important to note that not all individuals infected with EIEC will progress to the dysenteric form of the disease. Some may experience a milder course of illness characterized primarily by watery diarrhea, while others may remain asymptomatic. The severity and duration of symptoms can vary among individuals.

The dysenteric form of EIEC infection can be mistaken for other types of dysentery, including those caused by Shigella species. Therefore, proper laboratory testing, including stool culture and identification of the bacteria, is essential to accurately diagnose EIEC infection and differentiate it from other similar conditions.

In summary, the clinical features of an EIEC infection initially involve watery diarrhea. In some cases, the infection progresses to a dysenteric form of the disease, characterized by fever, chills, malaise, abdominal cramps, and the presence of blood and leukocytes in stool specimens. Prompt medical attention and appropriate laboratory testing are important for proper diagnosis and management of EIEC infection.

Diagnosis of Enteroinvasive E. coli (EIEC)

Diagnosing Enteroinvasive Escherichia coli (EIEC) can be challenging due to its similarities with Shigella species and other E. coli strains, including nonpathogenic ones. The identification of EIEC involves demonstrating that the organism possesses the biochemical profile of E. coli while exhibiting genotypic or phenotypic characteristics of Shigella species.

Here are some diagnostic methods commonly used for EIEC:

1. Detection of Virulence Marker Antigen (VMA) by ELISA: VMA is a plasmid-coded antigen associated with EIEC invasion. Enzyme-linked immunosorbent assay (ELISA) can be employed to detect the presence of VMA in bacterial samples, aiding in the identification of EIEC strains.
2. HeLa Cell Invasion Assay: This laboratory test involves incubating the bacterial isolate with HeLa cells, which are human epithelial cells commonly used in cell culture experiments. EIEC strains exhibit the ability to invade and multiply within HeLa cells. By observing the invasion and replication of the bacteria within the cells, EIEC can be differentiated from other non-invasive E. coli strains.
3. Sereny Test: The Sereny test is an in vivo test performed by inoculating a bacterial suspension, typically obtained from a stool sample, into the eyes of guinea pigs. If the strain is EIEC, it can cause conjunctivitis in the guinea pig, providing a positive indication for the presence of EIEC.
4. Biochemical and Phenotypic Characteristics: EIEC strains display certain atypical biochemical traits that distinguish them from other E. coli strains. They are non-motile, do not ferment lactose, and are negative for lysine decarboxylase activity. These characteristics can be assessed through biochemical tests, such as the IMViC (indole, methyl red, Voges-Proskauer, citrate) test series, and other specific biochemical assays.

It is worth noting that laboratory diagnosis of EIEC may require a combination of these diagnostic methods, along with additional tests to confirm the identification. Molecular techniques, such as polymerase chain reaction (PCR), can also be used to detect specific genetic markers associated with EIEC strains.

Accurate diagnosis of EIEC is crucial to differentiate it from other pathogens and nonpathogenic E. coli strains. This helps guide appropriate treatment strategies and public health measures, as EIEC infections may require specific interventions to prevent further transmission.

In summary, the diagnosis of Enteroinvasive Escherichia coli (EIEC) involves demonstrating the organism’s biochemical profile as E. coli with genotypic or phenotypic characteristics associated with Shigella species. Diagnostic methods include detecting Virulence Marker Antigen (VMA) by ELISA, performing HeLa cell invasion assays, conducting the Sereny test, and assessing the atypical biochemical and phenotypic characteristics of EIEC strains. A comprehensive approach utilizing these diagnostic methods and techniques can aid in the accurate identification of EIEC infections.

Treatment of Enteroinvasive E. coli (EIEC)

The treatment of Enteroinvasive Escherichia coli (EIEC) infections primarily focuses on supportive care to manage symptoms and prevent dehydration. In cases where antibiotic treatment is warranted, certain antibiotics can be used to target non-Shiga toxin-producing E. coli (non-STEC) strains, including EIEC.

Here are some key points regarding the treatment of EIEC:

1. Rehydration: Patients with profuse diarrhea or vomiting associated with EIEC infection should receive rehydration therapy. This involves replacing fluids and electrolytes to prevent or correct dehydration. Oral rehydration solutions containing a balanced amount of salts and sugars can be administered to replenish lost fluids.
2. Supportive Care: Symptomatic relief measures can be employed to manage abdominal cramps, fever, and other discomforts associated with EIEC infection. This may include over-the-counter antipyretics (fever reducers) and analgesics (pain relievers).
3. Antibiotic Treatment: In some cases, antibiotic therapy may be necessary, especially for severe or prolonged EIEC infections. The choice of antibiotics depends on factors such as the severity of symptoms, the susceptibility of the bacteria, and the patient’s individual circumstances. Commonly used antibiotics for treating non-STEC diarrheagenic E. coli, including EIEC, may include:

• Fluoroquinolones: Ciprofloxacin is an example of a fluoroquinolone antibiotic that can be effective against EIEC. However, it is essential to consider local antibiotic resistance patterns and the susceptibility of the specific strain before initiating treatment.
• Macrolides: Azithromycin, a macrolide antibiotic, is another option for treating EIEC infections. It may be used when fluoroquinolones are contraindicated or when there is a known susceptibility to macrolides.
• Rifaximin: Rifaximin is a non-absorbable antibiotic that targets the gastrointestinal tract. It may be considered for the treatment of EIEC infections, particularly in cases where other antibiotics are not suitable or in individuals with recurrent infections.

It is crucial to note that antibiotic treatment should be guided by the advice of healthcare professionals and local guidelines. Antibiotics should not be used indiscriminately and should be reserved for cases where the benefits outweigh the potential risks, especially considering the increasing concern of antibiotic resistance.

Additionally, it’s important to differentiate between EIEC and Shiga toxin-producing E. coli (STEC) infections. Antibiotics are generally not recommended for STEC infections, as they may increase the risk of developing hemolytic uremic syndrome (HUS), a severe complication associated with STEC infections.

In summary, the treatment of Enteroinvasive Escherichia coli (EIEC) infections primarily involves supportive care to manage symptoms and prevent dehydration. Antibiotic therapy may be considered in severe or prolonged cases, targeting non-STEC diarrheagenic E. coli strains. Fluoroquinolones (e.g., ciprofloxacin), macrolides (e.g., azithromycin), and rifaximin are among the antibiotics that may be used, although the choice should be guided by local antibiotic resistance patterns and individual patient considerations. Proper medical guidance is crucial in determining the appropriate treatment approach for EIEC infections.

Prevention of Enteroinvasive E. coli (EIEC)

Preventing Enteroinvasive Escherichia coli (EIEC) infections involves adopting measures to reduce the risk of exposure to the bacteria and practicing good hygiene. Here are some important preventive measures:

1. Food Safety: Proper food handling, preparation, and storage are crucial in preventing EIEC infections. Follow these guidelines:
   • Wash hands thoroughly with soap and water before handling food, after using the bathroom, and after changing diapers.
   • Ensure proper cooking of meat products, especially ground beef. Cook them to a safe internal temperature to kill bacteria.
   • Avoid consuming raw or undercooked foods, including meats, eggs, and unpasteurized dairy products.
   • Wash fruits and vegetables thoroughly before consumption, especially if eaten raw.
   • Prevent cross-contamination by separating raw and cooked foods, using separate cutting boards and utensils.
2. Safe Water and Sanitation:
   • Drink and use safe water sources. If uncertain about the safety of the water supply, opt for bottled water or boil water before consumption.
   • Avoid swallowing water while swimming in pools, lakes, or other recreational water bodies, as they can be potential sources of contamination.
   • Practice good sanitation and hygiene, particularly in areas with poor sanitation infrastructure. Proper disposal of human waste is essential to prevent contamination of water sources.
3. Personal Hygiene:
   • Wash hands thoroughly with soap and water, especially before eating, after using the bathroom, and after contact with animals.
   • Teach children proper handwashing techniques and ensure they follow them consistently.
   • Use hand sanitizers when soap and water are not readily available.
   • Avoid close contact with individuals who have diarrhea, and do not share personal items with them.
4. Travel Considerations:
   • Follow food and water precautions when traveling to regions with limited access to safe water and sanitation facilities.
   • Consume bottled or boiled water, and avoid consuming raw or undercooked foods in areas with questionable hygiene practices.
   • Adhere to proper hand hygiene practices during travel.
5. Public Health Measures:
   • Public health authorities should monitor and regulate food and water supplies to ensure safety standards are met.
   • Surveillance and monitoring of EIEC infections can help identify outbreaks and implement appropriate control measures.
   • Public education campaigns can raise awareness about EIEC and promote preventive measures among the general population.

By implementing these preventive measures, individuals can reduce their risk of EIEC infection. It is important to note that if symptoms suggestive of EIEC infection develop, such as diarrhea with blood or persistent symptoms, seeking medical attention and appropriate diagnosis are crucial for proper management and treatment.

FAQ

References

• Sastry A.S. & Bhat S.K. (2016). Essentials of Medical Microbiology. New Delhi : Jaypee Brothers Medical Publishers.
• Murray, P. R., Rosenthal, K. S., & Pfaller, M. A. (2013). Medical microbiology. Philadelphia: Elsevier/Saunders
• Parija S.C. (2012). Textbook of Microbiology & Immunology.(2 ed.). India: Elsevier India.
• https://asm.org/Articles/2019/March/Whats-the-Significance-of-Enteroinvasive-E-coli
• https://www.sciencedirect.com/topics/medicine-and-dentistry/enteroinvasive-escherichia-coli
• https://www.frontiersin.org/articles/10.3389/fmicb.2017.02390/full
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723341/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC517479/
• https://intermountainhealthcare.org/-/media/files/health-info/germwatch/gastroenteritis/shigella.pdf?la=en
• https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/escherichia-coli-diarrheagenic
• https://www.cdc.gov/mmwr/volumes/68/wr/mm6807a5.htm
• https://academic.oup.com/femsle/article/165/1/159/623712
• https://www.cambridge.org/core/services/aop-cambridge-core/content/view/49CD7555F9C59994FC043984D5D9BE65/S0950268897007413a.pdf/origin-and-characteristics-of-enteroinvasive-strains-of-escherichia-coli-eiec-isolated-in-germany.pdf
• https://www.amboss.com/us/knowledge/diarrheagenic-e-coli/
• https://www.sph.umn.edu/events-calendar/research-day/past-events/rd-2020/amanda-markelz/
• https://www.ajtmh.org/view/journals/tpmd/76/3/article-p528.xml
• https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-019-4659-y