Mycoplasma and Ureaplasma

Family: Mycoplasmataceae
Genus: Mycoplasma
Species: M. pneumoniae Species: M. hominis Species: M. genitalium

Genus: Ureaplasma
Species: U. urealyticum
16 species colonize humans, the above have been associated with disease.

Diseases Caused by Mycoplasma

Organism M. pneumoniae Disease Upper respiratory tract disease, tracheobronchitis, atypical pneumonia, (chronic asthma?) Pyelonephritis, pelvic inflammatory disease, postpartum fever Nongonococcal urethritis Nongonococcal urethritis, (pneumonia and chronic lung disease in premature infants?)

M. hominis

M. genitalium U. urealyticum

Note that: Other organisms in the family of Mycoplasmataceae infect humans but a disease association is not known.

Morphology and Physiology

Smallest free-living bacteria (0.2 - 0.8 mm) many can
pass through a 0.45 m filter, mistaken for viruses

Small genome size (M. pneumoniae is ~800 Kbp) Require complex media for growth Facultative anaerobes Except M. pneumoniae - strict aerobe Lack a cell wall, membrane contains sterols
no cell wall means these are resistant to penicillins, cephalosporins, vancomycin, etc.

Grow slowly by binary fission

Doubling time can be as long as 16 hours, extended incubation needed

Fried Egg Colonies of some Mycoplasmas

Colony morphology, contd

Except for M. pneumoniae colonies which have a granular appearance, described as being mulberry shaped

mulberry

Morphology and Physiology, contd

Require complex media for growth, including sterols Major antigenic determinants are glycolipids and proteins, some cross reaction with human tissues Requirements for growth allow one to differentiate between species
M. pneumoniae - glucose M. hominis - arginine U. urealyticum - urea (buffered media due to growth inhibition by alkaline media) M. genitalium - difficult to culture

Pathogenesis
Adherence
P1 pili (M. pneumoniae) Movement of cilia ceases (ciliostasis) Clearance mechanism stops resulting in cough

Toxic metabolic products

Peroxide and superoxide Inhibition of catalase

Immunopathogenesis
Activate macrophages Stimulate cytokine production Superantigen (M. pneumoniae) Inflammatory cells migrate to infection and release TNF-a then IL-1 and IL-6

Transmission electron photomicrograph of a hamster trachea ring infected with M. pneumoniae.

Note the orientation of the M. pneumoniae through their specialized tip-like organelle, which permits close association with the respiratory epithelium. M, mycoplasma; m, microvillus; C, cilia. Image used with permission. From Baseman and Tully, Emerging Infectious Diseases 3

Mycoplasma pneumoniae
Tracheobronchitis Atypical pneumonia (walking pneumonia) More common in school-age children and young adults but everyone is susceptible (theory that adults
might be partially immune due to previous exposure)

Estimate of 2,000,000 cases in USA annually, possibly resulting in 100,000 hospitalizations Not a reportable disease, so true incidence is not known

Epidemiology - M. pneumoniae
Occurs worldwide No seasonal variation
Proportionally higher in summer and fall

Epidemics occur every 4-8 year

Epidemiology - M. pneumoniae
Spread by aerosol route (Confined populations) Disease of the young (5-20 years), although all ages are at risk

Clinical Syndrome - M. pneumoniae

Tracheobronchitis
70-80% of infections

Pneumonia
Approximately 10% of infections
Mild disease but long duration Primary atypical pneumonia Walking pneumonia

Clinical Syndrome - M. pneumoniae

Incubation - 2-3 weeks Fever, headache and malaise Persistent, dry, nonproductive cough Respiratory symptoms Patchy bronchopneumonia, may precede symptoms acute pharyngitis may be present Organisms persist Slow resolution Rarely fatal Note: Muscle pain and GI symptoms usually not present

Immunity - M. pneumoniae
Complement activation
Alternative pathway

Phagocytic cells Antibodies

IgA important

Delayed type hypersensitivity

More severe disease (immunopathogenesis)

Laboratory Diagnosis - M. pneumoniae

Microscopy
Difficult to stain This process can help eliminate other organisms

Culture (definitive diagnosis)

Sputum (usually scant) or throat washings Special transport medium needed
Must suspect M. pneumoniae

May take 2-3 weeks or longer, 6 hour doubling time with glucose and pH indicator included Incubation with antisera to look for inhibition, not a typical test

Laboratory Diagnosis - M. pneumoniae

Serology
Complement fixation May take 4-6 weeks Fourfold rise in titer (requires collection two samples 3-4 weeks apart) Relatively insensitive Cold agglutinins 1/3 - 2/3 of patients I antigen Appear first Non-specific and insensitive ELISA Not commercially available

Laboratory Diagnosis - M. pneumoniae

Molecular diagnosis
PCR-based tests are being developed and these are expected to be the diagnostic test of choice in the future. These should have good sensitivity and be specific

Treatment and Prevention M. pneumoniae

Treatment
Tetracycline in adults (doxycycline) or erythromycin (children)
Newer fluoroquinolones (in adults)

Resistant to cell wall synthesis inhibitors

Prevention
Avoid close contact Isolation is not practical due to length of illness No vaccine, although attempted

M. hominis, M. genitalium and U. urealyticum

Clinical syndromes M. hominis - pyelonephritis, pelvic inflammatory disease and postpartum fever M. genitalium - nongonococcal urethritis U. urealyticum - nongonococcal urethritis Epidemiology Colonization at birth - usually cleared but could persist sexually active adults with M. hominis - 15% with U. urealyticum - 45% -75% Colonization with M. genitalium - ??

M. hominis, M. genitalium and U. urealyticum

Laboratory diagnosis
Culture (except M. genitalium)

Treatment and prevention

Treatment
Tetracycline or erythromycin U. urealyticum is resistant to tetracycline M. hominis is resistant to erythromycin and sometimes to tet, Clindamycin for these resistant strains

Prevention
Abstinence or barrier protection No vaccine