Mycoplasma And Chlamydia

Front 1

Mycoplasma and Ureaplasma: Physiology and structure

Back 1

Cell size: .1-.3 micron
Cell wall: absent
Atmosphere: Facultative aerobe
Nutritional requirement: sterols (then incorporated into cell membrane)
Nutritional supplements: vitamins, AA, nucleic acid precursors
Penicillin resistant (no cell wall!)

Front 2

Mycoplasma/Ureaplasma pathogens

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M. pneumoniae:
-respiratory tract
-URT disease, atypical pneumonia, tracheobronchitis
M. genitalium:
-GU tract
-Urethritis
U. urealyticum:
-RT, GU tract
-Urethritis

Front 3

Mycoplasma pneumoniae : PHYSIOLOGY AND STRUCTURE

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The smallest free-living bacterium; able to pass through 0.45-μm pore filters (“artificial bacterium”)

Highly pleomorphic and flexible cells; very difficult to stain

Absence of cell wall and a cell membrane containing sterols are unique among bacteria

Sterols are not synthesized; incorporated from host or serum in culture media; (time for colonies <1 week)

Slow rate of growth (generation time, 1 to 6 hours)
Strict aerobe

Front 4

Mycoplasma pneumoniae : clinical diseases

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Upper respiratory infections:
Atypical pneumonia, often termed “Walking pneumonia” mild chronic respiratory symptoms; can last for weeks

Dry non-productive cough with scant sputum; low grade fever, headache & malaise

Immune responses to M. pneumoniae infection
Early IgM, late IgG, IgA
Cell mediated immunity may protect
-Many different types/clones, cross protection is poor
In children, 50% develop secondary cold agglutinin disease
-Transient autoimmune disease caused by high levels of circulating antibody reactive with RBC

Front 5

Mycoplasma pneumoniae : virulence, pathogenesis

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Virulence factors

Surface structures:

P1 adhesin protein binds cilia leading to eventual loss of ciliated epithelial cells

Adhesions acts as superantigen, stimulating migration of inflammatory cells and release of TNF-alpha and Il-1

Capsule: polysaccharide, may be involved in attachment or may have additional toxic effects

Hemolysins: alpha or beta hemolysin (cytolytic) kill host cells

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Mycoplasma pneumoniae : epidemiology

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Worldwide disease with no seasonal incidence

Estimated 100,000 hospitalizations and 2 Million cases/yr in U.S.

Outbreaks occur in schools and where indoor crowding in restricted space is common

Transmitted by inhalation of aerosolized droplets

Strict human pathogen

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Mycoplasma pneumoniae: lab diagnosis

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Diagnosis of exclusion
Microscopy: no cell wall, don't stain
Culture: 2-6wks before positive dx and insensitive
Molecular diagnosis: PCR based amplification w/excellent sensitivity is test of choice, not routinely available
Cold agglutinin: Sensitivity 65%, poor specificity; cross reactions

Front 8

Mycoplasma pneumoniae: prevention and treatment

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No vaccine

Treat with macrolides

Front 9

Ureaplasma urealyticum

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Genitourinary tract
Benign carriage is common, esp. in women

Can cause nonspecific urethritis (men) or cervicitis (women).

Some have postulated as cause of infertility.

Diagnosis and epidemiology are virtually unexplored
Treatment: broad spectrum antibiotics

Front 10

Chlamydia overview

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Gram negative
Obligate intracellular pathogen

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Chlamydia life cycle

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Elementary body: Infectious form. Metabolically inactive.
Similar to an endospore

Reticulate body: replicative form. Grows until nutrients
within endosomal compartment are depleted, elementary bodies are formed, then released by endosomal fusion with cytoplasmic membrane.

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Cell envelope architecture of elementary bodies

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P layer– cysteine rich proteins that are highly
Crosslinked by disulfide bonds
Functional equivalent of peptidoglycan layer

Elementary body form has no peptidoglycan

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“Chlamydial anomaly”

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Peptidoglycan has not been detected in any Chlamydial
life stage
-Most studies are with elementary bodies

However….some β-lactam and cephalosporin drugs have
efficacy against Chlamydia

How can that be?
-Chlamydial genome sequences indicate that most of the enzymes in
peptidoglycan biosynthesis are present

Based on current data, reticulate bodies may have some unusual type of
peptidoglycan
-It’s not thick or heavily cross-linked
-Never been seen by EM
Role of PG may be more related to cell division than to osmotic protection

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Chlamydia trachomatis: clinical diseases

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Trachoma: Chronic, inflammatory granulomatous process of eye surface, leading to blindness

Adult inclusion conjunctivitis: Acute process with mucopurulent discharge, corneal infiltrates

Neonatal conjunctivitis: Acute process with mucopurulent discharge

Urogenital infections: Mucopurulent discharge in GU tract; asymptomatic infections common in women
May have mild symptoms in men... mild burning on urination

Front 15

Chlamydia trachomatis : sexually transmitted diseases

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Predominantly caused by serovars D-K

Men: non-gonococcal urethritis

Women: urethritis, cervicitis Sequelae: Pelvic Inflammatory disease, ectopic pregnancy, infertility

>10% of sexually active population infected, men are reservoir; 2.8 million new infections/yr in U.S.

LGV (serovars L1-L3): more tissue-invasive > inguinal lymphadenopathy

Neonatal infections from passage through infected birth canal: conjunctivitis, pneumonia

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Chlamydia trachomatis: physiology and structure

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Small, gram-negative rods with unusual cell envelope/cell wall

Strict human intracellular pathogen; energy parasite

Major outer membrane proteins are species specific

Two biovars associated with human disease: trachoma 15 serovars LGV; four serovars

Infects non-ciliated columnar, cuboidal, and transitional epithelial cells

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Chlamydia trachomatis: VIRULENCE & PATHOGENESIS

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Proposed Roles of Type III Secretion in Pathogenesis and Development:
Inhibition of phagolysosome fusion
Acquisition of host lipids and nutrients
Fusogenicity of early inclusions (IncA)
Induction of anti- and/or pro-apoptotic activities
Modulation of intracellular development

Delayed Type Hypersensitivity (Hsp60 as DTH agent)

Autoimmunity (immune response to Hsp60)

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Chlamydia trachomatis: EPIDEMIOLOGY, DIAGNOSIS

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Epidemiology

Most common sexually transmitted bacterial disease in US

Ocular trachoma worldwide with blindness developing in 7 to 9 million patients

LGV highly prevalent in Africa, Asia, and South America

Diagnosis

Culture is highly specific, relatively insensitive
-As a routine matter, this is not likely to be available to you


Molecular amplification tests with NA probes: PCR or LCR fast and accurate

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Chlamydia trachomatis: TREATMENT, PREVENTION & CONTROL

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Treat LGV, ocular or genital infections and newborn conjunctivitis or pneumonia with common antibiotics
  
Safe sex practices and prompt treatment of patient and sexual partners help control infections

Face washing (trachoma); education re: hygiene/transmission………No vaccine …. yet

Front 20

Chlamydia pneumoniae
Overview

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Wordwide distribution, >50% sero-prevalence

probably recently ‘jumped’ from an animal host to humans

Community-acquired pneumonia

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Chlamydia pneumoniae: Clinical features

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Murky
chronic bronchitis, asthma, exacerbation of COPD
lung cancer, stroke, sarcoidosis, reactive arthritis, MS, Alzheimer disease
strongest association with coronary heart disease:

Front 22

Chlamydia pneumoniae: Dx, Tx, prevention

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Dx not usually attempted
Tx: doxycycline, erythromycin for at least 10 days
No vaccine

Front 23

Chlamydia psittaci

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Respiratory infection (psittacosis) after exposure to wild exotic animals