Microbiology chapters
Helicobacter pylori and atypical bacteria
Helicobacter pylori (how it survives stomach acid, the diseases it causes, the tests and eradication therapy) and the atypical bacteria that cause atypical pneumonia and other infections: Mycoplasma pneumoniae, Chlamydia and Chlamydophila, Legionella and Rickettsia, with why beta-lactams do not work against them.
In 30 seconds
- H. pylori is a curved, flagellated, microaerophilic Gram-negative rod that survives stomach acid by making urease (ammonia buffers acid); its CagA and VacA factors drive inflammation; it causes chronic (antral) gastritis, most duodenal ulcers and many gastric ulcers, gastric adenocarcinoma and MALT lymphoma (a WHO group 1 carcinogen); diagnose with the urea breath test or stool antigen (non-invasive; stop PPIs 2 weeks before) or the rapid urease (CLO) test and histology at endoscopy; treat with PPI + two antibiotics (clarithromycin or metronidazole with amoxicillin).
- Atypical bacteria lack a normal cell wall or live inside cells, so they do not Gram stain well, are not cultured on routine media and do not respond to β-lactams; they cause atypical pneumonia (gradual, dry cough, headache, mild signs but a worse-looking X-ray) treated with macrolides or doxycycline: Mycoplasma pneumoniae (young adults, no cell wall, cold agglutinins with haemolysis, erythema multiforme), Chlamydophila pneumoniae, C. psittaci (birds) and Legionella (water systems, hyponatraemia, diarrhoea, confusion; urine antigen).
- Chlamydia trachomatis (obligate intracellular; elementary body infects, reticulate body divides) causes trachoma (serovars A–C: leading infectious cause of blindness), genital infection (D–K: commonest bacterial STI, PID, infertility), neonatal conjunctivitis and pneumonia, and LGV (L1–L3).
On this page
Helicobacter pylori
Microbiology
- Curved (spiral, S-shaped) Gram-negative rod with several polar flagella (moves through gastric mucus).
- Microaerophilic; oxidase +, catalase +, strongly urease +.
- Grows slowly (3–7 days) on enriched media under microaerophilic conditions.
- Lives in the mucus layer over the gastric epithelium, mainly the antrum; does not invade.
Virulence
| Factor | Role |
|---|---|
| Urease | Splits urea → ammonia + CO₂; ammonia neutralises acid around the organism and damages cells |
| Flagella | Motility through mucus |
| Adhesins (BabA) | Attach to gastric epithelium |
| CagA (cytotoxin-associated gene A) | Injected into cells; stronger inflammation; higher risk of ulcer and cancer |
| VacA (vacuolating cytotoxin) | Damages epithelial cells |
| LPS, phospholipases, catalase | Inflammation and survival |
Transmission: person to person (faecal-oral, oral-oral), usually in childhood; infection is very common in developing countries including Pakistan and usually lifelong without treatment.
Diseases
- Chronic active gastritis (type B, antral): the usual result; often asymptomatic.
- Duodenal ulcer: antral gastritis → less somatostatin → more gastrin and acid → gastric metaplasia in the duodenum, which H. pylori colonises. Most duodenal ulcers are linked to H. pylori.
- Gastric ulcer: a large share (the other main cause is NSAIDs).
- Gastric adenocarcinoma (intestinal type): via atrophic gastritis and intestinal metaplasia; H. pylori is a group 1 carcinogen (IARC).
- Gastric MALT lymphoma: low-grade B-cell lymphoma; often regresses after eradication.
- Associated: iron-deficiency anaemia, immune thrombocytopenia.
Diagnosis
| Test | Type | Notes |
|---|---|---|
| Urea breath test (¹³C or ¹⁴C urea) | Non-invasive | Labelled CO₂ in breath if urease present; best for confirming eradication (4 weeks after treatment) |
| Stool antigen test | Non-invasive | Good for diagnosis and confirming eradication |
| Rapid urease test (CLO test) | Invasive (gastric biopsy at endoscopy) | Colour change from urease; quick |
| Histology | Invasive | Silver (Warthin-Starry), Giemsa or H&E; shows gastritis grade, atrophy, metaplasia |
| Culture | Invasive | Antibiotic sensitivity (resistant cases) |
| Serology (IgG) | Non-invasive | Shows past or present infection; stays positive after cure, so not used to confirm eradication |
False negatives in breath, stool and urease tests: PPIs (stop 2 weeks before), antibiotics or bismuth (stop 4 weeks before), recent bleeding.
Treatment
- Triple therapy for 14 days: PPI + amoxicillin + clarithromycin (or metronidazole); where clarithromycin resistance is high (as in Pakistan), bismuth quadruple therapy (PPI + bismuth + tetracycline + metronidazole) or other regimens based on local guidance.
- Confirm eradication with a breath or stool test.
Atypical bacteria and atypical pneumonia
Why "atypical"
- Not seen on Gram stain (no cell wall or intracellular).
- Not grown on routine media.
- Not killed by β-lactams (no peptidoglycan target or hidden inside cells).
- Treated with macrolides (azithromycin, clarithromycin), tetracyclines (doxycycline) or respiratory fluoroquinolones.
Atypical pneumonia
- Gradual onset, low-grade fever, headache, malaise, myalgia, dry cough.
- Few chest signs but X-ray shows patchy or interstitial infiltrates that look worse than the patient ("walking pneumonia").
- White cell count often normal.
- Extrapulmonary features give clues (below).
| Organism | Key clues |
|---|---|
| Mycoplasma pneumoniae | Young adults, students, military recruits, outbreaks every few years; cold agglutinins (IgM against the I antigen of red cells → autoimmune haemolytic anaemia), erythema multiforme / Stevens-Johnson syndrome, bullous myringitis, arthralgia, encephalitis |
| Chlamydophila pneumoniae | Mild pneumonia, sinusitis, pharyngitis; linked to atherosclerosis in studies |
| Chlamydophila psittaci (psittacosis) | Contact with birds (parrots, pigeons, poultry); pneumonia, splenomegaly, headache |
| Legionella pneumophila (Legionnaires' disease) | Older smokers, immunosuppressed; contaminated water systems (air conditioning cooling towers, showers, hot tubs: aerosols; not person to person); high fever, confusion, diarrhoea, hyponatraemia, raised liver enzymes, relative bradycardia; Pontiac fever is a mild flu-like form |
| Coxiella burnetii (Q fever) | Farm animals (placentas, milk, dust); inhaled; pneumonia, hepatitis, endocarditis (culture-negative); spores resist drying |
Mycoplasma pneumoniae
- Smallest free-living bacteria; no cell wall (membrane contains sterols); pleomorphic.
- Not seen on Gram stain; slow growth on special media (Eaton agar) as "fried egg" colonies.
- Attaches to respiratory epithelium (P1 adhesin), stops ciliary action.
- Diagnosis: PCR on throat swab, serology (IgM), cold agglutinins (non-specific).
- Treatment: azithromycin, doxycycline, fluoroquinolones; β-lactams do not work.
- Ureaplasma urealyticum and Mycoplasma genitalium: urethritis.
Chlamydia
Biology
- Obligate intracellular bacteria (cannot make their own ATP: "energy parasites"); cell wall lacks typical peptidoglycan.
- Life cycle: the elementary body (small, dense, infectious, extracellular) enters cells → becomes the reticulate body (large, replicating, intracellular) → forms inclusion bodies (Halberstaedter-Prowazek bodies, glycogen-rich in C. trachomatis: iodine-staining) → converts back to elementary bodies, released on cell death.
Chlamydia trachomatis serovars
| Serovars | Disease |
|---|---|
| A, B, C | Trachoma: chronic keratoconjunctivitis spread by hands, flies, towels in poor hygiene → scarring, trichiasis, blindness (a leading infectious cause worldwide). WHO SAFE strategy: Surgery, Antibiotics (azithromycin), Facial cleanliness, Environmental improvement |
| D–K | Genital infection: the commonest bacterial STI; non-gonococcal urethritis, epididymitis, cervicitis (often silent), PID → infertility and ectopic pregnancy; reactive arthritis (urethritis, conjunctivitis, arthritis; HLA-B27); inclusion conjunctivitis in adults; neonatal conjunctivitis (5–14 days after birth) and neonatal pneumonia (staccato cough, 4–12 weeks) |
| L1, L2, L3 | Lymphogranuloma venereum: small painless genital ulcer → painful inguinal lymphadenopathy ("buboes"), groove sign, proctitis, strictures |
Diagnosis: NAAT (PCR) on urine or swabs (test of choice), Giemsa or iodine-stained inclusions, cell culture (McCoy cells), direct immunofluorescence.
Treatment: doxycycline (7 days) or azithromycin (single dose; used in pregnancy); erythromycin for neonates; treat partners; often co-treat gonorrhoea.
Rickettsiae (brief)
- Obligate intracellular Gram-negative coccobacilli; spread by arthropods (lice, fleas, ticks, mites) except Coxiella.
- Infect vascular endothelium → vasculitis: fever, headache, rash, eschar (scrub typhus, spotted fevers).
| Disease | Organism | Vector |
|---|---|---|
| Epidemic typhus | R. prowazekii | Body louse |
| Endemic (murine) typhus | R. typhi | Rat flea |
| Scrub typhus | Orientia tsutsugamushi | Mite (chigger); eschar; seen in South Asia |
| Spotted fevers (Rocky Mountain, Mediterranean) | R. rickettsii, R. conorii | Ticks; rash starting on wrists and ankles, spreading to palms and soles |
- Weil-Felix test: antibodies against rickettsiae cross-react with Proteus OX antigens (OX-19, OX-2, OX-K); old and non-specific. Modern tests: immunofluorescence, PCR.
- Treatment: doxycycline (even in children for serious rickettsial disease); chloramphenicol as an alternative.
Exam focus
Expect: H. pylori morphology, urease and acid survival, CagA and VacA, diseases (duodenal ulcer, gastric cancer, MALT lymphoma), tests (urea breath, stool antigen, CLO, serology limits) and the effect of PPIs, eradication regimens; features of atypical pneumonia and why β-lactams fail; Mycoplasma (no wall, cold agglutinins, erythema multiforme), Legionella (water systems, hyponatraemia, urine antigen, BCYE), psittacosis, Q fever; Chlamydia life cycle, serovars and diseases (trachoma, D–K genital and neonatal, LGV), NAAT and treatment; rickettsiae, vectors and Weil-Felix.
Quick revision
- H. pylori: curved, flagellated, microaerophilic, urease +; gastritis, duodenal ulcer, gastric cancer, MALT lymphoma.
- Tests: urea breath and stool antigen (non-invasive); CLO and histology (endoscopy); stop PPIs 2 weeks first.
- Treatment: PPI + amoxicillin + clarithromycin/metronidazole, or bismuth quadruple.
- Atypicals: no Gram stain, no routine culture, β-lactams useless; macrolides, doxycycline.
- Mycoplasma: no wall, cold agglutinins, young adults.
- Legionella: cooling towers, hyponatraemia, diarrhoea, urine antigen.
- Chlamydia: EB infectious, RB replicates; A–C trachoma, D–K genital/neonatal, L1–L3 LGV.
- Rickettsiae: arthropods, vasculitis, Weil-Felix; doxycycline.
Written by The House Job from standard microbiology references (Levinson's Review of Medical Microbiology and Immunology).
FAQ
How does H. pylori survive stomach acid?
It produces urease, which splits urea into ammonia that neutralises acid around the bacterium, and it lives in the protective mucus layer.
Which non-invasive tests diagnose H. pylori?
The urea breath test and the stool antigen test; both can also confirm eradication.
Why are beta-lactams ineffective against Mycoplasma?
Mycoplasma has no cell wall, which is the target of beta-lactam antibiotics.
Which features suggest Legionella pneumonia?
Exposure to contaminated water systems, high fever, confusion, diarrhoea, hyponatraemia and abnormal liver tests; the urine antigen test helps confirm it.