Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics (particularly penicillins and other beta-lactam antibiotics that target cell wall synthesis) and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or “walking” pneumonia, is the most clinically relevant species. Antibiotics, particularly macrolides, are the most effective mode of therapy.

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General Characteristics

  • Pleomorphic:
    • Pear-shaped or filamentous rod
    • Colonies have characteristic “fried egg” shape.
  • Cell membrane is composed of sterol: Sterol supplementation is required for growth in a laboratory.
  • No cell wall: therefore, does not gram stain
  • Requires growth media enriched with nucleic acids to grow
  • Smallest free-living bacteria


  • Virulence factors: 
    • P1 adherence protein: promotes adherence to the respiratory epithelium
    • Creation of reactive oxygen species: damages the respiratory epithelium
  • Reservoirs:
    •  Humans:
      • Asymptomatic carriers 
      • Symptomatic infected
  • Transmission:
    • Human-to-human transmission
      • M. pneumoniae: inhalation of aerosolized droplets and contact with fomites
      • M. hominis and M. genitalium: sexual contact 
    • Infected vectors are contagious for approximately 10 days from infection.
    • Transmission requires prolonged periods of close contact.
  • High-risk factors:
    • Age, primarily young adults 
    • Those living in close quarters:
      • Military recruits
      • Prisoners
Mechanisms of pathogenesis of mycoplasma pneumoniae

Mechanisms of pathogenesis: Mycoplasma pneumoniae

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Mycoplasma pneumoniae pathogenesis

Mechanisms of pathogenesis: Mycoplasma pneumoniae

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Diseases Caused by Mycoplasma

M. pneumoniae

Pathology caused by the M. pneumoniae bacterium is varied; however, diagnosis and treatment are standard:

  • Respiratory infection:
    • Atypical, or “walking” pneumonia:
      • Insidious-onset headache, malaise, low-grade fever, and non-productive cough
      • May be associated with autoimmune hemolytic anemia
    • Tracheobronchitis (bronchitis): 
      • Inflammation of bronchi
      • Presents with non-productive cough, fever, headache, sore throat, pharyngeal exudates, and cervical lymphadenopathy
    • Pharyngitis:
      • May precede pneumonia
      • Milder presentations of M. pneumoniae infection 
      • Resembles pharyngitis produced by non-exudative group A Streptococcus infections or viral pharyngitis
  • Mucocutaneous syndrome:
    • Mild urticarial rash
    • Erythema multiforme
    • Stevens-Johnson syndrome
    • M. pneumoniae–induced rash and mucositis (MPAM)
  • Central nervous system (CNS) involvement:
    • Direct infection: meningitis
    • Post-infective autoimmune inflammatory processes caused by cross-reaction of Mycoplasma antibodies with galactocerebroside:
      • Acute disseminated encephalomyelitis (ADEM)
      • Guillain-Barre
  • Hemolysis:
    • Infection causes alteration of I antigen on red blood cells → leads to immunoglobulin (IgM) production and autoimmune hemolysis
    • Seen in 60% of infections 
    • Usually self-limited, not requiring treatment
  • Diagnosis:
    • Clinical picture usually sufficient
    • Lab testing: 
      • Culture: grows on Eaton agar, but usually the polymerase chain reaction (PCR) is more sensitive
      • High titer of cold agglutinin (IgM)
      • Nucleic acid amplification (PCR)
    • Chest X-ray: diffuse interstitial infiltrates with no alveolar exudates (appear worse than expected compared to clinical symptoms)
  • Treatment:
    • Macrolides, tetracyclines, or respiratory fluoroquinolones
    • Penicillins (and other cell wall synthesis inhibitors) are ineffective because Mycoplasma have no cell wall.
Table: Compare and contrast Mycoplasma pneumonia with pneumococcal pneumonia
Characteristics Mycoplasma pneumonia Pneumococcal pneumonia
Type of pneumonia Atypical (interstitial) Typical (alveolar)
Preceding pharyngitis Common Never
Onset Gradual Sudden with chills
Fever Low grade High grade
Cough Non-productive, paroxysmal Productive
Pleuritic chest pain Absent Present
Leukocytosis Absent Present
Age of highest incidence Young adults < 30 years old Older adults
Complications Otitis media, erythema multiforme, hemolytic anemia, myocarditis, pericarditis, bullous otitis media Bacteremia, meningitis, otitis media

Mycoplasma hominis, Mycoplasma genitalium

  • Less common, known to cause disease of the urogenital tract:
    • Pyelonephritis
    • Pelvic inflammatory disease (PID)
    • Postabortal fever
    • Postpartum fever
  • Diagnosis:
    • Clinical suspicion in at-risk patients:
      • Immunocompromised
      • Preterm infants
      • Concomitant sepsis
    • Laboratory testing:
      • Culture: difficult and slow to grow
      • PCR testing: more rapid, but performed in few specialized centers
  • Treatment:
    • Tetracyclines
    • Fluoroquinolones
    • Clindamycin


  1. Kashyap, S., & Sarkar, M. (2010). Mycoplasma pneumonia: Clinical features and management. Lung India: Official organ of Indian Chest Society, 27(2), 75–85.
  2. Waites, K.B., & Taylor-Robinson, D. (2015). Mycoplasma and Ureaplasma. In the Manual of Clinical Microbiology, 11th ed, Jorgensen, J., Pfaller, M., Carroll, K., et al. (Eds), ASM Press, Washington DC. P. 1088.
  3. Baseman, J.B., & Tully, J.G. (1997). Mycoplasmas: Sophisticated, reemerging, and burdened by their notoriety. Emerg Infect Dis. Jan-Mar;3(1):21-32. doi: 10.3201/eid0301.970103. PMID: 9126441; PMCID: PMC2627593.
  4. Koskiniemi, M. (1993). CNS manifestations associated with Mycoplasma pneumoniae infections: Summary of cases at the University of Helsinki and review. Clin Infect Dis. Aug;17 Suppl 1(Suppl 1):S52-7. doi: 10.1093/clinids/17.supplement_1.s52. PMID: 8399938; PMCID: PMC7110383.

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