Mycoplasma pneumoniae
Mycoplasma pneumoniae is a tiny bacterium with no cell wall that causes atypical "walking pneumonia," most often in young people in close quarters. Its lack of a cell wall makes it invisible on Gram stain and resistant to penicillins.
Mycoplasma pneumoniae is one of the smallest free-living bacteria and is defined by a single structural fact: it has no cell wall. Its plasma membrane instead contains cholesterol for stability. Because Gram staining and beta-lactam antibiotics both target the cell wall, Mycoplasma cannot be seen on Gram stain and is intrinsically resistant to penicillins and cephalosporins.
Clinically, it is a leading cause of atypical (walking) pneumonia. Spread by respiratory droplets, it favors people under 30 and close-contact settings — military barracks, dormitories, prisons. The illness comes on gradually with headache, malaise, low-grade fever, and a persistent dry, nonproductive cough. A classic exam clue is the chest X-ray that looks worse than the patient: diffuse patchy or reticulonodular infiltrates in someone who appears only mildly ill.
Laboratory associations are high-yield. Mycoplasma infection can produce cold agglutinins — IgM antibodies that agglutinate red cells at low temperatures and can cause hemolytic anemia. It cannot be cultured on standard media, requiring special Eaton agar, so diagnosis is usually clinical or by PCR and serology. Treatment relies on antibiotics that do not target the cell wall: macrolides such as azithromycin, tetracyclines like doxycycline, or respiratory fluoroquinolones. Extrapulmonary complications include rash (including Stevens-Johnson syndrome in the young) and, rarely, neurologic disease.
USMLE Step 1 tests Mycoplasma pneumoniae as the prototypical wall-less organism: expect questions linking the missing cell wall to Gram stain invisibility and beta-lactam resistance, the walking pneumonia vignette, cold agglutinins, and macrolide treatment.
Key takeaways
- Mycoplasma pneumoniae lacks a cell wall, so it does not Gram stain and beta-lactams are useless against it.
- It causes atypical walking pneumonia with insidious onset and dry cough, classically in young people in close quarters.
- The chest X-ray often looks worse than the patient appears.
- Cold agglutinins (IgM) are associated and can cause hemolysis; its membrane uniquely contains cholesterol.
- Treat with macrolides, doxycycline, or fluoroquinolones — a standard USMLE Step 1 question pattern.