Curved and Spiral Gram Negative Organisms

This group is unified by a curved or spiral, comma-shaped or corkscrew, morphology, distinguishing it at a glance from the straight bacilli.

All four organisms in this section are motile via polar flagella. All four are primary gastrointestinal pathogens. This distinguishes them from the Enterobacterales, which cause GI disease only via specific pathotypes, and from the nonfermenters, which rarely cause primary GI disease at all.

Morphology. Gram negative, curved and comma-shaped rods, highly motile via a single polar flagellum.

Transmission. Faecal-oral, via contaminated water, is the dominant route. It is classically associated with inadequate sanitation infrastructure and large outbreaks following natural disasters or in refugee settings. Less commonly, transmission is via contaminated food, particularly raw or undercooked shellfish.

A comparatively high infectious dose is required in a host with normal gastric acidity, often cited around 10 to the 5th to 10 to the 8th organisms. The organism is acid-labile, and most ingested bacteria are killed in the stomach.

Conditions reducing gastric acid (proton pump inhibitor use, prior gastric surgery, achlorhydria) substantially lower the effective infectious dose and increase susceptibility.

Major virulence factors. Cholera toxin is a classic A-B exotoxin.

• The B subunit binds a specific intestinal epithelial cell surface receptor, ganglioside GM1.
• The A subunit ADP-ribosylates a G-protein, causing persistent activation of adenylate cyclase and a sustained rise in intracellular cAMP.
• Via this pathway, massive efflux of chloride and water enters the intestinal lumen, producing the characteristic profuse, watery diarrhoea.

Toxin-coregulated pili mediate intestinal colonisation. They also serve as the receptor for the bacteriophage that carries the cholera toxin genes; the toxin genes themselves are phage-encoded.

Disease. Cholera is characterised by profuse, watery, rice-water stool, pale, flecked with mucus, classically odourless or with a mild fishy smell. It produces rapid, severe dehydration and, in untreated severe cases, hypovolaemic shock and death within hours.

The diarrhoea is noninvasive and nonbloody, reflecting the toxin-mediated rather than tissue-invasive mechanism. This is a key distinguishing feature from the invasive, inflammatory dysenteric illnesses caused by organisms such as Shigella or EIEC.

Diagnosis. Clinical diagnosis is often sufficient in an outbreak or endemic setting given the highly characteristic presentation. Stool culture on selective media, thiosulfate-citrate-bile salts-sucrose agar (TCBS), confirms the diagnosis and supports outbreak investigation.

The mainstay of management is aggressive oral or intravenous rehydration. Mortality is overwhelmingly a consequence of fluid loss rather than direct toxin- or tissue-mediated organ damage. Rehydration alone dramatically reduces mortality even without antibiotic treatment.

Morphology. Gram negative, curved rods, motile.

Transmission. Ingestion of raw or undercooked seafood, particularly shellfish. Oysters are a classic vehicle, reflecting the organism's natural marine and estuarine habitat. It also causes wound infection following exposure of a break in the skin to contaminated seawater.

Major virulence factors. Thermostable direct haemolysin, associated with the Kanagawa phenomenon, contributes to intestinal invasion and tissue damage. This is mechanistically and clinically distinct from the purely toxin-mediated, noninvasive pathophysiology of V. cholerae.

Disease. A common cause of seafood-associated gastroenteritis. It typically causes self-limited watery diarrhoea, abdominal cramping, nausea, and low-grade fever. Diarrhoea is occasionally inflammatory or bloody, given the organism's greater invasive tendency compared to V. cholerae.

Wound infection following seawater exposure can range from mild cellulitis to severe, rapidly progressive soft tissue infection in patients with underlying liver disease or immunosuppression.

Diagnosis. Stool or wound culture on selective media, TCBS, as for V. cholerae. A seafood exposure history is the key clinical clue prompting specific consideration of this organism.

Morphology. Gram negative, curved or spiral rods, occasionally described as gull-wing or S-shaped when two organisms align end to end. Motile, with a characteristic darting, corkscrew motility on wet preparation.

Transmission. Faecal-oral, predominantly via ingestion of undercooked poultry (the single most common source), unpasteurised dairy, and contaminated water. It is also acquired from direct contact with infected domestic animals. Puppies and kittens with diarrhoeal illness are a recognised, specific source, particularly relevant in young children.

Major virulence factors. Invasion of intestinal epithelium produces an inflammatory enterocolitis. Molecular mimicry between specific Campylobacter surface lipooligosaccharide structures and human peripheral nerve gangliosides is the mechanistic basis of the organism's most distinctive postinfectious complication, Guillain-Barre syndrome.

Disease. The most common bacterial cause of gastroenteritis in many high-income settings. It presents with fever, abdominal pain (which can be severe enough to mimic appendicitis), and diarrhoea that is frequently bloody or inflammatory given the organism's invasive tendency.

Postinfectious complications include reactive arthritis, part of the broader postenteric reactive arthritis association shared with Salmonella, Shigella, and Yersinia.

Most distinctively, Guillain-Barre syndrome, an acute demyelinating polyneuropathy, is triggered by the molecular mimicry mechanism. Campylobacter jejuni is the single most commonly identified antecedent infection in patients presenting with Guillain-Barre syndrome.

Diagnosis. Stool culture requires specific selective media and microaerophilic incubation conditions, reflecting the organism's microaerophilic oxygen requirement. Incubation is at an elevated temperature, 42 degrees Celsius, exploiting the organism's thermotolerance relative to most competing stool flora. Stool PCR panels are increasingly used given superior sensitivity and turnaround time compared to culture.

Morphology. Gram negative, spiral and helical rods, highly motile via multiple polar flagella, specifically adapted to burrow through the protective gastric mucus layer.

Transmission. Person-to-person, likely predominantly faecal-oral and oral-oral, though the precise dominant route remains incompletely defined. Acquisition typically occurs in childhood. Prevalence strongly correlates with lower socioeconomic status and household crowding. Chronic colonisation, once established, often persists for life if untreated.

Major virulence factors. Urease is the organism's defining and diagnostically central virulence factor. It hydrolyses urea to ammonia and carbon dioxide, locally neutralising gastric acid around the bacterium and allowing it to survive within the otherwise hostile acidic gastric environment.

CagA, cytotoxin-associated gene A, is injected directly into host gastric epithelial cells via a type IV secretion system. It is associated with more severe inflammation and a substantially increased risk of the malignant complications.

VacA, vacuolating cytotoxin, induces epithelial cell vacuolation and apoptosis, contributing to mucosal damage.

Disease.

• Chronic gastritis: the organism is now recognised as the dominant cause of chronic gastritis worldwide.
• Peptic ulcer disease, both gastric and duodenal ulceration: it is a major cause, via chronic inflammation and disruption of normal mucosal protective mechanisms.
• Malignancy: it is a recognised carcinogen, causally linked to gastric adenocarcinoma and gastric MALT (mucosa-associated lymphoid tissue) lymphoma.

MALT lymphoma has a distinctive property: a substantial proportion of early-stage cases regress with successful H. pylori eradication alone, without conventional oncological chemotherapy or radiotherapy. This is a genuinely distinctive treatment principle among malignancies generally.

Diagnosis. Multiple modalities are available, each with different practical trade-offs.

The urea breath test has the patient ingest labelled urea. Labelled CO2 is detected in exhaled breath if urease-producing H. pylori is present. It is a noninvasive test of active infection. The stool antigen test is noninvasive and also detects active infection.

Serology detects prior exposure and antibody, but cannot reliably distinguish active from past cleared infection. This limits its usefulness for confirming cure.

Endoscopic biopsy with rapid urease testing, histology, or culture is invasive. It allows direct visualisation of gastric pathology and, where needed, culture for antibiotic susceptibility testing in cases of treatment failure.

Proton pump inhibitor use in the weeks before testing can suppress the organism sufficiently to cause a false-negative urea breath test or stool antigen result. This is an important point when interpreting a negative test in a patient on acid suppression therapy.