Campylobacter jejuni: Morphology, Pathogenesis, Virulence Factors, Diagnosis, Treatment & Prevention

Table of Contents

• Introduction
• Taxonomy and Classification
• Morphology and Microscopy
• Cultural and Growth Characteristics
• Biochemical Tests
• Pathogenesis
• Virulence Factors
• Epidemiology
• Transmission
• Clinical Manifestations
• Laboratory Diagnosis
• Treatments
• Prevention and Control
• Antimicrobial Resistance
• Conclusion
• References 

Introduction to Campylobacter jejuni 

• Campylobacter jejuni is a Gram-negative, curved or spiral-shaped bacterium and one of the leading bacterial causes of campylobacteriosis, a foodborne gastrointestinal infection.
• The bacterium commonly inhabits the intestinal tract of animals, particularly poultry, which serves as an important reservoir for human infection.
• Humans can become infected primarily by consuming undercooked or contaminated poultry and other meat, contaminated water, or unpasteurized milk.
• Infection typically affects the gastrointestinal system and may cause fever, diarrhea, abdominal pain, abdominal cramps, and nausea.
• In some individuals, C. jejuni infection can lead to serious post-infectious complications, most notably Guillain–Barré syndrome (GBS), a neurological disorder that can cause muscle weakness and, in severe cases, paralysis.

Taxonomy and Classification of Campylobacter jejuni

• Domain: Bacteria
• Kingdom: Pseudomonadati
• Phylum: Campylobacterota
• Class: Campylobacteria
• Order: Campylobacterales
• Family: Campylobacteraceae
• Genus: Campylobacter
• Species: Campylobacter jejuni

Morphology and Microscopy of Campylobacter jejuni

• Campylobacter jejuni is a Gram-negative, curved, rod-shaped or spiral-shaped bacterium.
• It characteristically exhibits a “gull-wing” appearance, particularly when two curved cells are joined together.
• The cells are approximately 0.2–0.8 µm in width and 0.5–5.0 µm in length.
• C. jejuni is motile, with amphitrichous flagella that facilitate movement.
• It is non-spore-forming.
• Following Gram staining, C. jejuni appears microscopically as slender, curved, spiral, or S-shaped Gram-negative rods, often showing the distinctive gull-wing configuration.

Cultural and Growth Characteristics of Campylobacter jejuni

• Campylobacter jejuni is microaerophilic, requiring approximately 3–10% oxygen (O₂) for growth.
• It is also capnophilic, preferring an atmosphere containing approximately 5–10% carbon dioxide (CO₂).
• The organism can grow over a temperature range of approximately 30–47°C, with higher temperatures favoring C. jejuni compared with many other enteric bacteria.
• The optimum pH for growth is approximately 5.5–7.0.
• C. jejuni generally requires selective culture media for isolation because it grows relatively slowly and can be overgrown by other microorganisms present in clinical specimens.

Skirrow’s Medium (Horse Blood Agar)

• C. jejuni produces small, gray, smooth colonies with a flat to low-convex profile.
• Colonies are typically moist and slightly translucent and may exhibit slight spreading across the agar surface.
• Skirrow’s medium contains selective antibiotics such as vancomycin, polymyxin B, cephalothin, and trimethoprim, which suppress many competing bacteria and facilitate the isolation of Campylobacter species from clinical specimens.

Sheep Blood Agar

• Colonies are typically small, gray, flat, smooth, moist, and non-hemolytic.
• Selective formulations may contain antibiotics such as bacitracin, colistin, cephalothin, and actidione, which inhibit many competing bacteria and fungi and facilitate the isolation of Campylobacter species from clinical specimens.

Butzler Medium

• C. jejuni typically forms small, round to irregular colonies.
• Colonies are generally smooth, moist, and translucent to slightly opaque in appearance.

Biochemical Tests of Campylobacter jejuni

Biochemical Test	Result
Gram Staining	Negative
Catalase	Positive
Oxidase	Positive
H₂S Production	Negative
KOH Test	Positive
Nitrate Reduction	Positive
Nitrite Reduction	Negative
OF (Oxidative-Fermentative) Test	Non-fermentative
Urease	Negative
Glucose Fermentation	Negative
DNase	Negative
Hippurate Hydrolysis	Positive
Indoxyl Acetate Hydrolysis	Positive
Alkaline Phosphatase	Variable
Arylsulfatase	Negative
Tween 40 Hydrolysis	Positive
Tween 60 Hydrolysis	Positive
Tween 80 Hydrolysis	Negative

Pathogenesis of Campylobacter jejuni

• Transmission: Campylobacter jejuni infection is most commonly acquired by consuming contaminated or undercooked food, particularly poultry and pork, as well as unpasteurized milk or untreated water. Direct contact with infected animals can also transmit the bacterium.
• Survival and intestinal colonization: After ingestion, the bacteria survive passage through the gastrointestinal tract and reach the jejunum and ileum of the small intestine, where they colonize the intestinal mucosa.
• Motility: C. jejuni uses its polar flagella and chemoreceptors to move through the intestinal mucus. Its characteristic corkscrew-like motility helps it penetrate the mucus layer and reach epithelial cells.
• Adhesion to host cells: The bacterium produces several surface-associated adhesion proteins that facilitate attachment to intestinal epithelial cells. Important adhesins include CadF, FlpA, JlpA, and FlaA, which contribute to binding and colonization of host cells.
• Invasion: C. jejuni produces Campylobacter invasion-associated (Cia) proteins, including CiaB, CiaC, CiaD, and CiaI, which promote bacterial internalization into intestinal epithelial cells.
• Intracellular survival: Following internalization, C. jejuni can reside within a membrane-bound compartment known as the Campylobacter-containing vacuole (CCV), where the bacterium can survive and multiply.
• Virulence factors: Disease development involves multiple Campylobacter virulence-associated factors, including adhesion molecules, chemotaxis proteins, flagellar components, invasion factors, and toxins. Together, these factors facilitate colonization, epithelial invasion, tissue damage, and inflammation.
• Cytolethal Distending Toxin (CDT): CDT is an important toxin produced by C. jejuni and consists of three subunits: CdtA, CdtB, and CdtC.
• CdtA and CdtC primarily function as binding components that help deliver the active CdtB subunit to intestinal epithelial cells.
• CdtB has DNase activity, causing DNA damage in host cells.
• DNA damage can result in cell-cycle arrest, cellular distension, and reduced viability of enterocytes, contributing to intestinal injury.
• Host immune response: Infection stimulates the intestinal immune system and promotes the release of inflammatory mediators, including interleukin-8 (IL-8). IL-8 attracts neutrophils and other immune cells to the site of infection, producing a strong local inflammatory response.
• Intestinal inflammation and diarrhea: The combined effects of bacterial adhesion, invasion, toxin-mediated cellular damage, and host inflammatory responses disrupt normal intestinal epithelial function and contribute to abdominal pain, inflammation, and diarrhea.
• Overall mechanism: The pathogenesis of C. jejuni can therefore be summarized as ingestion → intestinal colonization → motility through mucus → adhesion → invasion → toxin-mediated damage → immune activation → intestinal inflammation and diarrhea.

Virulence Factors of Campylobacter jejuni

Flagella

• Facilitate bacterial movement through the intestinal mucus layer.
• Help C. jejuni reach and colonize the intestinal epithelial surface.
• Contribute to motility and host-cell interactions.

Chemotaxis

• Enables the bacterium to sense and respond to environmental signals.
• Directs bacterial movement toward favorable conditions and away from harmful environments.
• Helps C. jejuni locate and colonize suitable niches within the gastrointestinal tract.

Adhesins

• Surface-associated proteins that mediate the attachment of bacteria to intestinal epithelial cells.
• Are essential for initial colonization and persistence within the host.
• Important adhesins include CadF, FlpA, JlpA, and other surface-associated proteins.

Invasion Proteins

• Promote the entry of C. jejuni into host epithelial cells.
• Facilitate intracellular survival and contribute to bacterial dissemination and tissue damage.

Lipooligosaccharide (LOS)

• Acts as an endotoxin-like component of the outer membrane.
• Stimulates a strong host inflammatory response and contributes to intestinal inflammation.
• Structural variation in LOS is also associated with some post-infectious complications, including Guillain–Barré syndrome.

Cytolethal Distending Toxin (CDT)

• Causes DNA damage in host cells through the DNase activity of its CdtB subunit.
• Leads to cell-cycle arrest and, at sufficient levels, cell death/apoptosis.
• Contributes to intestinal epithelial injury and mucosal damage.

Campylobacter Invasion Proteins (Cia Proteins)

• Include proteins such as CiaB, CiaC, CiaD, and CiaI.
• Promote invasion of intestinal epithelial cells.
• Contribute to intracellular survival and persistence of the bacterium.

Epidemiology of Campylobacter jejuni

• Campylobacter jejuni is widely distributed worldwide and is one of the leading causes of bacterial gastroenteritis and foodborne diarrheal disease. It is responsible for approximately 90% of human campylobacteriosis cases.
• Historically, bacteria resembling Campylobacter were described by Theodor Escherich in 1886 in stool samples from children with diarrhea. Human Campylobacter infections were subsequently recognized and isolated from diarrheal stool specimens in clinical laboratories during the 1970s.
• Poultry, particularly chickens and turkeys, are major reservoirs of C. jejuni. Other important animal reservoirs include cattle, pigs, and other livestock, which may carry the organism asymptomatically in their intestines.
• Human infection occurs primarily through the fecal–oral route, especially by consuming undercooked or contaminated poultry and other meat, unpasteurized milk, or contaminated water. Direct contact with infected animals can also result in transmission.
• Cross-contamination during food preparation is an important source of infection because poultry carcasses may carry high numbers of Campylobacter.
• C. jejuni has a low infectious dose, meaning that ingestion of a relatively small number of organisms may be sufficient to cause illness.
• In developing countries, infection is often endemic and the greatest burden occurs among young children, particularly those younger than 2 years of age.
• In developed countries, infection occurs across all age groups, with relatively high incidence among young adults.
• Campylobacter infections frequently show seasonal variation, with cases increasing during warmer months, particularly in temperate regions. The exact seasonal pattern varies geographically.
• In the United States, approximately 2.1–2.4 million cases of campylobacteriosis have been estimated to occur annually.
• Most human infections are sporadic, although foodborne and waterborne outbreaks can occur.
• Clinical disease generally develops 2–5 days after exposure and commonly presents with acute diarrhea, which may be watery or bloody, abdominal cramps, abdominal pain, and fever.
• Most infections are self-limiting, but post-infectious complications can occasionally occur, including Guillain–Barré syndrome (GBS) and reactive arthritis.
• Guillain–Barré syndrome is a particularly important complication because certain C. jejuni strains possess lipooligosaccharide (LOS) structures that can mimic host gangliosides, potentially triggering an autoimmune response affecting the peripheral nervous system.
• Key epidemiological factors include contaminated poultry and other foods, inadequate food handling, consumption of unpasteurized milk or untreated water, animal exposure, young age, and seasonal variation.

Transmission of Campylobacter jejuni

Campylobacter jejuni is transmitted primarily through the fecal–oral route, most commonly through contaminated food, water, or contact with infected animals.

Foodborne Transmission

• The most common route of transmission is consumption of contaminated food, particularly raw or undercooked poultry such as chicken.
• Cross-contamination can occur when raw meat contaminates ready-to-eat foods, utensils, cutting boards, or hands during food preparation.
• Infection can also result from consuming unpasteurized milk and dairy products contaminated with C. jejuni.

Waterborne Transmission

• Infection may occur through consumption of contaminated drinking water or exposure to contaminated recreational water, including streams and lakes.
• Waterborne transmission is associated with inadequate sanitation and agricultural runoff, which can introduce animal fecal material into water sources.

Animal-to-Human Transmission

• Important animal reservoirs include poultry, cattle, sheep, dogs, and cats.
• Humans may become infected through direct contact with infected animals or their feces, particularly when proper hand hygiene is not practiced.

Person-to-Person Transmission

• Person-to-person transmission is uncommon but can occur, particularly in settings where maintaining proper hygiene is difficult, such as daycare centers and long-term care facilities.
• Transmission may occur through fecal contamination of hands, surfaces, or other objects.

Clinical Manifestations of Campylobacter jejuni

• Symptoms of C. jejuni infection usually develop 2–5 days after exposure and most cases resolve within approximately 7 days.
• The infection primarily causes acute gastroenteritis, although the severity and duration of symptoms can vary.

Acute Gastroenteritis

• Usually lasts 5–7 days, although symptoms may persist longer in some individuals.
• Abdominal pain: Often severe and cramp-like and may resemble appendicitis.
• Fever: Commonly ranges from approximately 38–40°C.
• Diarrhea: Often begins as watery diarrhea and may become bloody as intestinal inflammation develops.
• Nausea and vomiting: May occur, particularly during the early phase of infection.
• Malaise and fatigue: General weakness, tiredness, and feeling unwell may accompany the gastrointestinal symptoms.

Intestinal Infection

• C. jejuni can cause inflammation of the jejunum, ileum, and colon.
• Damage and ulceration of the intestinal mucosa may result in a dysentery-like illness, characterized by bloody diarrhea, abdominal pain, and intestinal inflammation.

Dehydration

• Persistent diarrhea and vomiting can result in significant fluid and electrolyte loss, particularly in young children and older adults.
• Signs in children and adults may include:
• Reduced frequency of urination
• Excessive thirst
• Very dark-colored urine
• Dizziness
• Dry or warm skin
• Signs in babies and toddlers may include:
• Fewer wet diapers or reduced urination
• Few or no tears when crying
• Reduced interest in playing or usual activities
• Unusual or extreme sleepiness

Complications

• Although most infections are self-limiting, some patients may develop complications, including:
• Irritable bowel syndrome (IBS)
• Reactive arthritis
• Guillain–Barré syndrome (GBS): A rare neurological complication that can cause tingling, muscle weakness, and loss of reflexes, typically beginning in the legs and potentially progressing to the arms and upper body. Severe cases may involve facial weakness, difficulty speaking or swallowing, breathing problems, and paralysis.
• Bacteremia and sepsis: People with weakened immune systems are at increased risk of invasive infection, in which bacteria can enter the bloodstream and potentially lead to sepsis, a life-threatening systemic response to infection.

Warning Signs of Severe Illness

• Severe or persistent dehydration
• High fever
• Confusion or disorientation
• Rapid heart rate
• Difficulty breathing
• Severe or worsening pain or discomfort

Note: A temperature of 103°F (39.4°C) or higher, confusion, difficulty breathing, or signs of severe dehydration should be treated as medical warning signs requiring prompt evaluation.

Laboratory Diagnosis of Campylobacter jejuni

Sample Collection and Transportation

• Fresh stool is the preferred specimen for diagnosis of intestinal C. jejuni infection.
• A rectal swab may be collected when a stool specimen is unavailable.
• Blood cultures are mainly indicated when bacteremia or sepsis is suspected, particularly in immunocompromised patients.
• Intestinal biopsy specimens may be examined in rare cases.
• Specimens should be collected in a clean, sterile container and transported promptly to the laboratory.
• Cary-Blair transport medium can be used when immediate processing is not possible.
• If processing is delayed, stool specimens should generally be kept at approximately 4°C according to laboratory protocols.
• Prolonged exposure to oxygen and drying should be avoided because Campylobacter is sensitive to environmental conditions.

Microscopy

• Direct examination of stool may be performed using contrast microscopy or Gram staining.
• On Gram staining, C. jejuni appears as slender, curved, comma-shaped, S-shaped, or spiral Gram-negative rods, sometimes showing a characteristic gull-wing appearance.
• Microscopy can provide a rapid presumptive indication of infection but has limited sensitivity and specificity.
• A definitive diagnosis generally requires culture or a validated molecular/antigen detection method.

Culture

• Stool specimens can be inoculated onto selective media and incubated under microaerophilic conditions.
• Skirrow’s Medium (Horse Blood Agar): Produces small, gray, smooth, moist, flat to low-convex colonies that may be slightly translucent and show limited spreading.
• Sheep Blood Agar: Produces small, gray, flat, smooth, moist, generally non-hemolytic colonies.
• Butzler Medium: Produces small, round to irregular, smooth, moist colonies that are typically translucent to slightly opaque.
• Suspected colonies are subsequently examined by microscopy and biochemical or molecular methods for identification.

Biochemical Identification

Following culture, suspected colonies can be evaluated using biochemical tests. Typical characteristics of C. jejuni include:

Test	Result
Gram Staining	Negative
Catalase	Positive
Oxidase	Positive
H₂S Production	Negative
KOH Test	Positive
Nitrate Reduction	Positive
Nitrite Reduction	Negative
OF Test	Non-fermentative

Molecular Methods

• Polymerase Chain Reaction (PCR): PCR-based assays can rapidly detect Campylobacter DNA in stool specimens and provide sensitive identification.
• Nucleic Acid Amplification Tests (NAATs): These methods detect specific Campylobacter nucleic acid sequences and generally provide faster results than culture. They do not require viable organisms for detection.
• Molecular methods are particularly useful when rapid diagnosis is required or when organisms may be difficult to recover by culture.
• RT-PCR: Reverse-transcription PCR is primarily designed for detecting RNA targets and is not the routine molecular method for detecting the DNA genome of C. jejuni. Therefore, for a website focused on bacterial diagnosis, it is more accurate to emphasize PCR and other NAATs rather than describing RT-PCR as the standard method.

Immunoassays

• Stool-based immunoassays can rapidly detect Campylobacter-specific antigens.
• They can provide results faster than conventional culture but may have different sensitivity and specificity depending on the assay used.
• Positive or unexpected results may require confirmation using culture or molecular testing, depending on the diagnostic laboratory protocol.

Diagnostic approach:

Stool collection → transport → microscopy (presumptive) → selective culture and/or NAAT → biochemical/molecular confirmation → identification of C. jejuni.

Treatments of Campylobacter jejuni

• Campylobacter jejuni infection is usually mild and self-limiting, with most patients recovering without antibiotic treatment.
• Supportive care is the mainstay of treatment, while antibiotics are reserved for severe, prolonged, or high-risk infections.

Supportive Treatment

• Oral Rehydration Therapy (ORT): Helps replace fluids and electrolytes lost through diarrhea and prevent dehydration.
• Intravenous Fluids: May be required for patients with severe dehydration or those unable to maintain adequate oral fluid intake.
• Antipyretics and Analgesics: Medications such as paracetamol (acetaminophen) may be used to relieve fever and discomfort. NSAIDs such as ibuprofen should be used cautiously, particularly in dehydrated patients.

Antibiotic Therapy

• Antibiotics may be considered for severe disease, prolonged symptoms, bacteremia, or patients at increased risk of complications.
• Azithromycin is generally preferred when antibiotic treatment is indicated because macrolide resistance is lower than resistance to fluoroquinolones in many settings.
• Erythromycin may also be used as an alternative macrolide.
• Ciprofloxacin may be considered only when the isolate is known or expected to be susceptible because fluoroquinolone-resistant Campylobacter is common in many regions.

Management of Complications

• Guillain–Barré Syndrome (GBS): Requires hospitalization and specialized supportive and neurological care, particularly when muscle weakness or respiratory involvement develops.
• Reactive Arthritis: Management may include anti-inflammatory medications and other treatment based on the severity and persistence of symptoms.
• Antimotility drugs: Agents such as loperamide are generally not recommended in bloody or severe diarrhea, as they may potentially worsen or prolong certain invasive diarrheal infections.

Prevention and Control of Campylobacter jejuni

• Cook poultry thoroughly: Properly cook chicken and other poultry to a safe internal temperature before consumption to destroy C. jejuni.
• Handle seafood safely: Avoid consuming raw or undercooked seafood and fish, and follow appropriate food-safety practices during preparation.
• Avoid unpasteurized dairy: Do not consume unpasteurized milk or dairy products, as they may contain Campylobacter.
• Prevent cross-contamination: Use separate cutting boards and utensils for raw meat and ready-to-eat foods. Thoroughly clean and disinfect food-contact surfaces after handling raw meat.
• Use safe drinking water: Drink treated, clean, and microbiologically safe water.
• Avoid untreated water: Do not drink untreated water from rivers, lakes, streams, springs, or wells, as these sources may be contaminated with animal feces.
• Maintain proper sanitation: Adequate sewage disposal, sanitation systems, and protection of water sources help prevent fecal contamination and reduce transmission.
• Practice proper hand hygiene: Wash hands thoroughly with soap and water after handling raw meat, using the toilet, touching animal feces, and before eating or preparing food.
• Practice safe animal handling: Maintain good hygiene when handling poultry, livestock, pets, and other animals.
• Avoid contact with animal feces: Minimize direct contact with animal feces and use appropriate protective measures when working on farms, in slaughterhouses, or in other high-risk occupational settings.
• Restrict food handling by infected individuals: People with active diarrhea or suspected Campylobacter infection should avoid preparing food for others until they have recovered and follow local public-health guidance.
• Practice pet hygiene: Wash hands after touching pets, pet food or water bowls, bedding, toys, feces, or urine, particularly before eating or preparing food.

Antimicrobial Resistance of Campylobacter jejuni

• Antimicrobial resistance (AMR) in Campylobacter jejuni is an increasing public-health concern because resistant strains can make campylobacteriosis more difficult to treat, particularly in severe or invasive infections.
• Antimicrobial resistance may contribute to prolonged illness and treatment failure and can significantly complicate management of patients with bacteremia.
• Resistance to fluoroquinolones, particularly ciprofloxacin, is a major concern. Resistance to macrolides such as azithromycin and erythromycin is generally less common but is also increasing in some regions.
• A 1994 study reported ciprofloxacin-resistant C. jejuni among U.S. military personnel stationed in Thailand. The study also reported substantial macrolide resistance among isolates from personnel in Hat Yai.
• Experimental studies in chickens demonstrated that exposure of fluoroquinolone-susceptible C. jejuni to fluoroquinolones could select for fluoroquinolone-resistant strains, highlighting the role of antimicrobial use in resistance development.
• In Europe, following the introduction of fluoroquinolones for use in poultry during the early 1990s, fluoroquinolone-resistant Campylobacter strains were subsequently detected more frequently among human infections.
• In the United States, a rise in domestically acquired ciprofloxacin-resistant Campylobacter infections was reported in Minnesota following the approval of fluoroquinolone use in poultry.
• A 1997 Minnesota study found ciprofloxacin resistance among C. jejuni isolates recovered from retail chicken, demonstrating that antimicrobial-resistant strains can occur within the food-production chain.
• The major factors contributing to AMR include antimicrobial use in food-producing animals, selection pressure, transmission of resistant strains through the food chain, and international spread.
• Because fluoroquinolone resistance is widespread, macrolides such as azithromycin are generally preferred when antibiotic treatment of campylobacteriosis is indicated, while susceptibility patterns should guide treatment where available.
• Responsible antimicrobial use in both human medicine and agriculture, together with food-safety measures and surveillance, is essential for controlling the emergence and spread of resistant C. jejuni strains.

Conclusion

• Campylobacter jejuni is a Gram-negative, curved, microaerophilic bacterium and a major cause of bacterial gastroenteritis worldwide.
• Infection is primarily acquired through contaminated or undercooked food, particularly poultry, as well as unpasteurized milk and contaminated water.
• The bacterium colonizes the intestinal tract and commonly causes acute inflammatory diarrhea, abdominal cramps, fever, and sometimes bloody stools.
• Although most infections are self-limiting, complications can occasionally develop, including Guillain–Barré syndrome (GBS), irritable bowel syndrome (IBS), and reactive arthritis.
• Increasing antimicrobial resistance, particularly to fluoroquinolones, presents an important challenge for treatment and highlights the need for responsible antimicrobial use.
• Effective prevention depends on proper food hygiene, thorough cooking of poultry, avoidance of unpasteurized products and untreated water, proper hand hygiene, and prevention of cross-contamination.
• Overall, early recognition, appropriate supportive care, and effective food-safety and infection-control practices are essential for reducing the burden of C. jejuni infection.

References 

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