Mycoplasma and Ureaplasma

Mycoplasma and Ureaplasma species possess no peptidoglycan cell wall at all. They are the only medically important bacteria that lack this structure entirely. Almost every other distinctive biological and clinical characteristic of these organisms follows from this.

Absence of cell wall. This is the single defining structural feature of the genus. It is distinct from cell-wall-deficient forms of otherwise walled bacteria, which are a transient, induced state rather than an intrinsic species characteristic.

These organisms do not Gram stain, as they have no cell wall to differentially retain or lose the stain. They cannot be reliably visualised by standard Gram microscopy at all. This is a genus-defining diagnostic limitation.

Sterol-containing membrane. A peptidoglycan wall normally provides rigidity. Here the cell membrane itself is reinforced by incorporation of sterols (cholesterol), obtained from the host environment because these organisms cannot synthesise sterols themselves.

This is unusual among bacteria, as most bacterial membranes lack sterols entirely. It also complicates culture, since specialised, sterol-enriched media are required for laboratory growth.

Pleomorphic morphology. Without a rigid cell wall to enforce a fixed shape, these organisms are pleomorphic, ranging from small coccoid forms to filamentous forms. Most other bacterial groups are identified by a fixed, characteristic shape: coccus, bacillus, spirochete.

Intrinsic resistance to beta-lactams. This is the direct and clinically critical pharmacological consequence of having no cell wall. Beta-lactam antibiotics, and glycopeptides such as vancomycin, act specifically on cell wall peptidoglycan synthesis or cross-linking. They have no target in these organisms and are entirely ineffective.

The resistance is intrinsic, not acquired, and applies regardless of any in vitro susceptibility testing result that might otherwise be obtained for other bacteria. Effective treatment instead relies on agents targeting protein or nucleic acid synthesis, principally macrolides, tetracyclines, and fluoroquinolones.

Transmission. Respiratory droplets. It spreads efficiently in settings of close, prolonged contact: schools, military barracks, university dormitories, households. The incubation period is relatively long compared with most other common respiratory pathogens.

Disease. It is the classic cause of walking pneumonia, an atypical, community-acquired pneumonia. It is particularly common in children and young adults. It is generally milder and more insidious in onset than typical bacterial pneumonia.

The dry cough is often prominent, persistent, and disproportionately severe relative to other symptoms. The chest examination and radiographic appearance can seem discordantly mild or patchy compared with the cough and systemic symptoms reported.

A range of extrapulmonary manifestations occur. In most cases they reflect immune-mediated mechanisms rather than direct organism invasion of the affected tissue.

• Erythema multiforme and other mucocutaneous eruptions. M. pneumoniae is a recognised infectious trigger for Stevens-Johnson syndrome in some cases.
• Haemolytic anaemia via cold agglutinins: IgM antibodies cross-reacting with the I antigen on red blood cells. The organism's membrane glycolipid antigens share structural similarity with this red cell surface antigen, a molecular mimicry mechanism.
• Less commonly, neurological complications (encephalitis, Guillain-Barre syndrome) and cardiac involvement.

Diagnosis. PCR from a respiratory specimen is increasingly the standard approach, given superior sensitivity and turnaround time. Serology with paired acute and convalescent samples remains used in some settings, because a single result cannot reliably distinguish current from past infection. The organism's fastidious, slow growth on specialised sterol-enriched media makes routine culture impractical for acute clinical diagnosis.

Transmission. Sexual contact.

Disease. It is an increasingly recognised cause of nongonococcal urethritis in men and cervicitis or pelvic inflammatory disease in women. The clinical picture overlaps substantially with Chlamydia trachomatis infection, so specific molecular testing is needed to distinguish the two.

Neither organism is reliably identified by standard Gram stain or culture, given their diagnostic limitations: obligate intracellular growth for Chlamydia, absent cell wall and fastidious growth for Mycoplasma.

Diagnosis. PCR-based testing, as routine culture is impractical. The organism grows exceptionally slowly even by mycoplasmal standards, often taking weeks to months, which makes culture essentially unusable for clinical diagnosis.

Resistance patterns. Increasing macrolide resistance is an emerging and clinically significant concern, relevant to evolving treatment guideline recommendations for confirmed infection.

General features. Ureaplasma is closely related to Mycoplasma and shares its defining absence of a cell wall and sterol-dependent membrane. It is distinguished by a specific biochemical property: the ability to hydrolyse urea, which gives the genus its name. This is a key laboratory identification feature.

Reservoir. It commonly colonises the lower genital tract of sexually active adults, frequently as asymptomatic colonisation rather than active infection. This matters when interpreting a positive genital tract test, since detection does not automatically equate to clinically significant disease.

Disease associations. Its pathogenic role is less certain and more debated than that of the more clearly established organisms elsewhere in bacteriology, reflecting its frequent presence as asymptomatic colonising flora.

• It is implicated in some cases of nongonococcal urethritis.
• Of particular neonatal significance, it is associated with chorioamnionitis.
• In preterm and very-low-birth-weight infants it is associated with neonatal respiratory disease. A contributory role in bronchopulmonary dysplasia in some very preterm infants has been proposed, reflecting ascending intrauterine infection in at-risk pregnancies.

Diagnosis. PCR-based testing where clinically indicated. Interpret with particular caution given the organism's frequent asymptomatic colonisation. A positive result must be considered alongside the clinical context rather than treated as automatically diagnostic of active disease.