MICROBIO 5.4

Mycobacterium

Mycolic acid

Chains of 60-90 carbons that produce wax-like lipid

Characteristics of mycolic acid

• Slow growth (synthesis time to produce mycolic acid)

  • antibiotic resistance —> antibiotic cleared from body before it has affect

• Protection from lysis after phagocytosis

• Intracellular growth

• Protected from desiccation ( remain viable in dried respiratory droplets up to EIGHT months)

• Resistance to gram stain, detergents, antimicrobial drugs

  • use ACID FAST

What is responsible for tuberculosis (AKA Consumption)

Mycobacterium tuberculosis

M. TB shape

Bacillus (rod)

M. TB gram status

positive (stains poorly)

M. TB motility

nonmotile

M. TB catalase activity

positive

M. TB Oxygen requirements

aerobe

M.TB Virulence factors

• Cord factor

  • tethers bacterial cells together

  • toxic to human cells and dec effectiveness of neutrophils and immune cells

• Drug resistance

  • mutations to certain antibiotics

**Not very virulent (5% infected develop disease) but kills 50% of infected

What does “M. TB has high G + C” mean?

They have a high guanine and cytosine content in their DNA

TB is the ___(th) leading cuase of death from infection & a major cause of death in the ___ and ____ population.

4th, HIV, AIDS

TB pathogenesis

1. transmission from inhalation of infected respiratory droplets

2. alveolar macrophage phagocytose bacteria, but it’s resistant to lysis

3. bacteria survive & multiply within macrophage

   • macrophage dies & releases bacteria

   • MORE macrophages come and engulf bacteria

   • THOSE macrophages die and release… and a cycle begins

4. immune cells (T cells), alerted to foreign antigens, produce tubercle around infection

5. Collagen fibers form around tubercle & cells in the center die

   • those dead cells release bacteria & cause caseous necrosis

6. Tubercle ruptures & bacteria released to establish active infection (AKA secondary/reactivated TB)

How is M. TB resistant to lysis?

It inhibits the fusion of its endocytic vesicle to the lysosome of phagocyte

Tubercle

nodular lesion

Caseous necrosis

cheese-like consistency in the middle of a TB tubercle formed from dead cell lipids and proteins

Disseminated TB

Macrophage bring bacterium to distant organs and tissues (e.g. bone marrow, spleen, kidney, brain)

Signs & symptoms of TB

• minor cough, fever….

• difficulty breathing, fatigue, weight loss, chest pain, wheezing…

• cough up blood & severe weight loss

  • patients experience muscle wasting at end stage

Muscle wasting

Body uses so much energy that we turn to break down muscle

Diagnosis of TB

• Tuberculin skin test

• Chest x-ray (tubercles in lungs)

• Acid fast staining on sputum samples

• Florescence microscopy using antibodies to identify bacteria

Tuberculin Skin Test (AKA Mantoux skin test)

1. Tuberculin is injected into dermis of forearm

2. 48-72 hours later, diameter of induration is measured

3. Infected will be large because of immune response of prior exposure

**TB patients have hypersensitivity skin rxn (delayed type) to a protein purified from tubercle bacillus

Induration

Raised area of injection

Induration of 5mm or more is a positive test for:

• immunocompromised

• history of TB

• in close contact with someone who has TB

• patient with fibrotic chest x-ray

Induration of 10mm or more is a positive test for:

• those who live/work in TB endemic areas

• younger than 4 yrs

• w/ underlying condition

• residents of long term facilities/shelters

• injection drug users

Induration of 15mm or more is a positive test for:

ANYONE

TB diagnosis if someone is vaccinated

• molecular tests —> test for presence of bacteria DNA

• interferon gamma release assay

  • blood sample, mixed with BACTERIA antigen

  • measure response of immune cells in blood samples

  • if with disease, immune response will be high

TB treatment

1. Four antibiotics for eight weeks

   • INH (isoniazid)

   • RIF (rifampin)

   • PZA (pyrazinamide)

   • EMB (ethambutol)

2. INH & RIF for 18 weeks MORE

** if inconsistent, TB may develop resistance

MDR- TB & XDR-TB

Multi-Drug resistant TB and extensively-drug resistant TB

Does NOT respond to first line antibiotics (INH, RIF, PZA, EMB)

Require treatment up to TWO YEARS

TB prevention

Vaccination —> BCG

What causes leprosy?

Mycobacterium LEPRAE

M. Leprae gram status

positive

M. Leprae shape

bacillus

M. Leprae staining

Acid-fast

M. Leprae optimal temperature

30 degrees C

M. Leprae transmission pathway

Direct contact via airborne droplets (secretions of respiratory system)

**rarely transmitted

Leprosy

AKA Hansen’s disease; affects nerves, skin, mucus membranes of upper respiratory tract & eyes

M. Leprae can have an incubation period of up to ___ ______.

20 years

Two forms of leprosy

1. Tuberculoid leprosy

2. Lepromatous leprosy

Tuberculoid leprosy

Non progressive (immune system successfully eliminated bacterium)

Skin lesions & loss of sensation

Usually robust immune system

Lepromatous leprosy

Destroys body’s tissues

Disfigured limbs & facial features

Leprosy Diagnosis

Based on signs of disease (e.g. disfigurements, legions)

Lepromin skin test (like TB skin test)

Culture & stain patient sample thru acid-fast stain

Leprosy Treatment

Long-term multi-drug therapy