mycoplasmas and there pathogenesity.

1. Mycoplasmas

2. MYCOPLASMAS
 There are more than 200 known species in the class of Mollicutes (cell
wall–free bacteria).
 At least 16 of these species are thought to be of human origin; others
have been isolated from animals and plants.
 In humans, four species are of primary importance:
 Mycoplasma pneumoniae
 Mycoplasma hominis
 Ureaplasma urealyticum
 Mycoplasma genitalium
 Mycoplasmas are the smallest organisms that can be free living in
nature and self-replicating on laboratory media.

3. In humans, four species are of primary
importance:
1. Mycoplasma pneumoniae causes pneumonia and has been
associated with joint and other infections.
2. Mycoplasma hominis sometimes causes postpartum fever and
has been found with other bacteria in uterine tube infections.
3. Ureaplasma urealyticum is a cause of nongonococcal urethritis in
men and is associated with lung disease in premature infants of
low birth weight.
4. Mycoplasma genitalium is closely related to M pneumoniae and
has been associated with urethral and other infections.
Other members of the genus Mycoplasma are pathogens of the
respiratory and urogenital tracts and joints of humans and animals.

4. They have the following characteristics:
(1) the smallest mycoplasmas are 125–250 nm in size;
(2) they are highly pleomorphic because they lack a rigid cell wall
and instead are bounded by a triple-layered “unit membrane”
that contains a sterol (mycoplasmas require the addition of
serum or cholesterol to the medium to produce sterols for
growth);
(3) Mycoplasmas are completely resistant to penicillin because they
lack the cell wall structures at which penicillin acts, but they are
inhibited by tetracycline or erythromycin;

5. (4) mycoplasmas can reproduce in cell-free media; on agar, the
center of the whole colony is characteristically embedded
beneath the surface;
(5) growth of mycoplasmas is inhibited by specific antibody;
(6) mycoplasmas have an affinity for mammalian cell
membranes.
The smallest genome of mycoplasmas, M genitalium , is little
more than twice the genome size of certain large viruses.

6. Morphology and Identification
A. Typical Organisms
 Mycoplasmas cannot be studied by the usual bacteriologic
methods because of the small size of their colonies and the
plasticity and delicacy of their individual cells.
 Growth in fluid media gives rise to many different forms.
 Growth on solid media consists principally of protoplasmic
masses of indefinite shape that are easily distorted.
 These structures vary greatly in size, ranging from 50 to 300 nm
in diameter.
 The morphology appears different according to the method of
examination (eg, dark field, immunofluorescence, Giemsa stained
films from solid or liquid media, and agar fixation).

7. B. Culture
 Culture of mycoplasmas that cause disease in humans requires
media with serum, a metabolic substrate such as glucose or urea,
and growth factors such as yeast extract.
 There is no one medium that is optimal for all the species because
of different properties and substrate requirements. After
incubation at 37°C for 48–96 hours, there may be no turbidity in
broth cultures;
 however, Giemsa stains of the centrifuged sediment show the
characteristic pleomorphic structures, and subculture on
appropriate solid media yields minute colonies.

8.  After 2–6 days on biphasic (broth over agar) and agar medium
incubated in a Petri dish that has been sealed to prevent
evaporation, isolated colonies of the more rapidly growing
mycoplasmas measuring 20–500 μm can be detected with a hand
lens.
 These colonies are round, with a granular surface and a dark
center typically buried in the agar.
 They can be subculture by cutting out a small square of agar
containing one or more colonies and streaking this material on a
fresh plate or dropping it into liquid medium.
 The organisms can be stained for microscopic study by placing a
similar square on a slide and covering the colony with a cover
glass onto which an alcoholic solution of methylene blue and
azure has been poured and then evaporated (agar fixation).
 Such slides can also be stained with specific fluorescent antibody.

9. C. growth Characteristics
 Mycoplasmas are unique in microbiology because of
(1) their extremely small size
(2) their growth on complex but cell-free media.
 Mycoplasmas pass through filters with 450-nm pore size and thus are
comparable to chlamydia or large viruses.
 However, parasitic mycoplasmas grow on cell-free media that
contain lipoprotein and sterol.
 This sterol requirement for growth and membrane synthesis is
unique.

10.  Many mycoplasmas use glucose as a source of energy;
ureaplasmas require urea.
 Some human mycoplasmas produce peroxides and hemolyze
red blood cells. In cell cultures and in vivo, mycoplasmas
develop predominantly at cell surfaces.
 Many established animal and human cell culture lines carry
mycoplasmas as contaminants;
 often the mycoplasmas are intracellular.

11. Pathogenesis
 Many pathogenic mycoplasmas have flasklike or filamentous
shapes and have specialized polar tip structures that mediate
adherence to host cells.
 These structures are a complex group of interactive proteins,
adhesins (eg, the P1 adhesin of M pneumoniae and the MgPa
adhesin of M genitalium), and adherence- accessory proteins.
 The proteins are proline rich, which influences the protein
folding and binding and is important in the adherence to cells.
 The mycoplasmas attach to the surfaces of ciliated and
nonciliated cells, probably through the mucosal cell
sialoglycoconjugates and sulfated glycolipids.

12.  Some mycoplasmas lack the distinct tip structures but use
adhesin proteins or have alternative mechanisms to adhere to
host cells.
 The subsequent events in infection are less well understood but
may include several factors as follows:
1. Direct cytotoxicity through generation of hydrogen peroxide
and superoxide radicals.
2. Cytolysis mediated by antigen–antibody reactions or
3. By chemotaxis and action of mononuclear cells, and
Competition for and depletion of nutrients.

13. Mycoplasmal Infection
 The mycoplasmas appear to be host specific, being
communicable and potentially pathogenic only within a single
host species.
 In animals, mycoplasmas appear to be intracellular parasites
with a predilection for mesothelial cells (pleura, peritoneum,
and synovia of joints). Several extracellular products can be
elaborated (eg, hemolysins).

14. A. Infection of Humans
 Mycoplasmas have been cultivated from human mucous membranes
and tissues, particularly from the genital, urinary, and respiratory
tracts.
 Mycoplasmas are part of the normal microbiota of the mouth and
can be grown from normal saliva, oral mucous membranes, sputum,
or tonsillar tissue.
 M salivarium, M orale, and other mycoplasmas can be recovered
from the oral cavities of many healthy adults, but an association with
clinical disease is uncertain.
 M hominis is found in the oropharynx of fewer than 5% of adults.
 M pneumoniae in the oropharynx is generally associated with disease.

15.  Some mycoplasmas are inhabitants of the genitourinary tract,
particularly in women.
 In both men and women, genital carriage of mycoplasmas is
directly related to the number of lifetime sex partners.
 M hominis can be cultured from 1% to 5% of asymptomatic men
and 30–70% of asymptomatic women; the rates increase to 20%
and more than 90% positive for men and women, respectively, in
sexually transmitted disease clinics.
 U urealyticum is found in the genital tracts of 5–20% of sexually
active men and 40–80% of sexually active women.
 Approximately 20% of women attending sexually transmitted
disease clinics have M genitalium in their lower genital tracts.
 Other mycoplasmas also occur in the lower genital tract.

16. B. Infection of Animals
 Bovine pleuropneumonia is a contagious, occasionally lethal
disease of cattle associated with pneumonia and pleural effusion.
 The disease probably has an airborne spread.
 Mycoplasmas are found in inflammatory exudates.
 Agalactia of sheep and goats in the Mediterranean area is a
generalized infection with local lesions in the skin, eyes, joints,
udder, and scrotum; it leads to atrophy of lactating glands in
females.

17.  Mycoplasmas are present in blood early and in milk and
exudates later.
 In poultry, several economically important respiratory diseases
are caused by mycoplasmas.
 The organisms can be transmitted from hen to egg to chick.
Swine, dogs, rats, mice, and other species harbor mycoplasmas
that can produce infection, particularly involving the pleura,
peritoneum, joints, respiratory tract, and eye.
 In mice, a Mycoplasma species of spiral shape (spiroplasma)
can induce cataracts.

18. Treatment
 Many strains of mycoplasmas are inhibited by a variety of
antimicrobial drugs, but most strains are resistant to penicillins,
cephalosporins, and vancomycin.
 Tetracyclines and erythromycins are effective both in vitro and
in vivo and are, at present, the drugs of choice in mycoplasmal
pneumonia.
 Some ureaplasmas are resistant to tetracycline.

19. Epidemiology, Prevention, and Control
 M pneumoniae behaves like a communicable viral respiratory
pathogen (see later discussion) and is capable of causing both
endemic and epidemic infections.
 The genital mycoplasmas and ureaplasma are spread by genital
or oral–genital contact and may be transmitted along with other
sexually acquired pathogens.
 Safe sexual practices should reduce spread.
 No vaccines are available to protect against any of these
organisms.

20. MYCOPLASMA PNEUMONIAE AND
ATYPICAL PNEUMONIAS
M pneumoniae is a prominent cause of pneumonia, especially in
persons 5–20 years of age.
Pathogenesis
 M pneumoniae is transmitted from person to person by means of
infected respiratory secretions.
 Infection is initiated by attachment of the organism’s tip to a
receptor on the surface of respiratory epithelial cells (Figure 25-1).
 Attachment is mediated by a specific adhesin protein on the
differentiated terminal structure of the organism.
 During infection, the organisms remain extracellular.

21. Figure 25-1
Electron micrograph of
Mycoplasma pneumoniae
attached to ciliated
respiratory epithelial cells
in a sputum sample
from a patient with culture-
proved Mycoplasma
pneumoniae
pneumonia.
The organisms (M) are seen
on the luminal border
attached between cilia (C).
(Courtesy AM Collier,
Department of
Pediatrics, University of
North Carolina.)

22. Clinical Findings
 Mycoplasmal pneumonia is generally a mild disease.
 The clinical spectrum of M pneumoniae infection ranges from
asymptomatic infection to serious pneumonitis, with
occasional neurologic and hematologic (ie, hemolytic anemia)
involvement and a variety of possible skin lesions.
 Bullous myringitis occurs in spontaneous cases and in
experimentally inoculated volunteers.

23.  The incubation period varies from 1 to 3 weeks.
 The onset is usually insidious, with malaise, fever, headache, sore
throat, and cough.
 Initially, the cough is nonproductive, but it is occasionally
paroxysmal.
 Later there may be blood-streaked sputum and chest pain.
 Early in the course, the patient appears only moderately ill, and
physical signs of pulmonary consolidation are often negligible
compared with the striking consolidation seen on radiographs.
 Later, when the infiltration is at a peak, the illness may be severe.
 Resolution of pulmonary infiltration and clinical improvement
occur slowly over 1–4 weeks. Although the course of the illness is
exceedingly variable, death is very rare and is usually attributable
to cardiac failure.

24.  Complications are uncommon, but hemolytic anemia may occur.
 The most common pathologic findings are interstitial with
peribronchial pneumonitis and necrotizing bronchiolitis.
 Other diseases possibly related to M pneumoniae include erythema
multiforme; central nervous system involvement, including meningitis,
meningoencephalitis, and mono- and polyneuritis; myocarditis;
pericarditis; arthritis; and pancreatitis.
 Common causes of community-acquired bacterial pneumonia, in
addition to M pneumoniae, include Streptococcus pneumoniae,
Legionella pneumophila, Chlamydia pneumoniae, and Haemophilus
influenzae.
 The clinical presentations of these infections can be very similar, and
recognition of the subtleties of signs and symptoms is important.
 The causative organisms must be determined by sputum examination
and culture, blood culture, and other tests.

25. Treatment
Tetracyclines, macrolides, or fluoroquinolones can produce
clinical improvement but do not eradicate M pneumoniae,
possibly because of their ability to reside intracellularly as well as
extracellularly.

26. Epidemiology, Prevention, and Control
 M pneumoniae infections are endemic all over the world.
 In populations of children and young adults, where close contact
prevails, and in families, the infection rate may be high (50–90%),
but the incidence of pneumonitis is variable (3–30%). For every case
of frank pneumonitis, there exist several cases of milder respiratory
illness.
 M pneumoniae is apparently transmitted mainly by direct contact
involving respiratory secretions.
 Second attacks are infrequent.
 The presence of antibodies to M pneumoniae has been associated
with resistance to infection but may not be responsible for it.
 Cell-mediated immune reactions occur.
 The pneumonic process may be attributed in part to an
immunologic response rather than only to infection.

27. MYCOPLASMA HOMINIS
 M hominis has been associated with a variety of diseases but is a
demonstrated cause in only a few of them.
 The evidence for a causal relationship in disease is from culture and
serologic studies.
 M hominis can be cultured from the upper urinary tract in about 10%
of patients with pyelonephritis.

28.  M hominis is strongly associated with infection of the uterine
tubes (salpingitis) and tubo-ovarian abscesses; the organism can
be isolated from the uterine tubes of about 10% of patients with
salpingitis but not from women with no signs of disease.
 Women with salpingitis more commonly have antibodies against
M hominis than women with no disease.
 M hominis has been isolated from the blood of about 10% of
women who have postabortal or postpartum fever and
occasionally from joint fluid cultures of patients with arthritis.

29. UREAPLASMA UREALYTICUM
 U urealyticum, like M hominis, has been associated with a variety of
diseases but is a demonstrated cause in only a few of them.
 U urealyticum, which requires 10% urea for growth, causes
nongonococcal, nonchlamydial urethritis in men.
 Recent data show that urethritis is associated with biovar 2 and not
biovar 1 (Ureaplasma parvum).
 U urealyticum is common in the female genital tract, where the
association with disease is weak.
 U urealyticum has been associated with lung disease in premature
low-birth-weight infants who acquired the organism during birth,
but a causal effect has not been clearly demonstrated.

30.  However, in a symptomatic neonate with radiographic
abnormalities in the lung and the absence of another
discernible cause for the pneumonia, treatment for
Ureaplasma species and M hominis seems warranted.
 The evidence that U urealyticum is associated with
involuntary infertility is at best marginal.

31. MYCOPLASMA GENITALIUM
 M genitalium was originally isolated from urethral cultures of
two men with nongonococcal urethritis, but culture of M
genitalium is difficult, and subsequent observations have been
based on data obtained by using NAATs and serologic data.
 The data suggest that M genitalium in men is associated with
some cases of acute as well as chronic nongonococcal urethritis.
 In women, M genitalium has been associated with a variety of
infections such as cervicitis, endometritis, salpingitis, and
infertility.

32. SUMMARY
• There are more than 200 species in the class Mollicutes (cell
wall–free bacteria), but only 16 are known to be associated
with human diseases.
• The major pathogens of medical importance include M
pneumoniae, the cause of endemic and epidemic respiratory
infections, and the urogenital mycoplasmas, M hominis, M
genitalium, and U urealyticum.
• M hominis and U urealyticum are easily cultivatable because
of rapid growth and less stringent requirements; M
genitalium and M pneumoniae require a much longer
incubation.

33. • M pneumoniae is an important cause of communityacquired
pneumonia. Infection is insidious and often protracted.
Diagnosis is best made clinically and confirmed by serology
(fourfold rise in IgG or IgM) or by NAATs or both.
• The urogenital Mycoplasmas have been associated with
nonchlamydial, nongonococcal urethritis in men (U
urealyticum). Both M hominis and U urealyticum may cause
postpartum fever and respiratory infections in premature
infants. M hominis is more prevalent in women with bacterial
vaginosis than in healthy women.
• Mycoplasma and Ureaplasma infections do not respond to β-
lactam antibiotics. Tetracyclines, macrolides, and quinolones
are the agents of choice.