Mycobacteria Flashcards
How many species are included in the mycobacterium tuberculosis complex (MTC)?
12
What is the morphology of Mycobacterium tuberculosis?
- Thin, straight rods
- Acid-fast
- Appear red in Ziehl–Neelsen stain against the blue counterstain (methylene blue)
What are the constituents of the mycobacterial cell wall?
- Mycolic acids, esterified to glycerol, trehalose, or arabinogalactans
- Trehalose dimycolate (TDM, cord factor): prevents chemotaxis of leukocytes, gives in vitro broth cultures a serpentine appearance
- Trehalose monomycolate
- Lipoarabinomannan: a virulence factor
- Peptidoglycan
- Phosphatidyl mannosides: prevent phagosome–lysosome fusion
What secretion system is utilized by mycobacteria?
Type VII
What are the growth characteristics of mycobacteria?
- Obligate aerobes
- Derive energy from oxidation of simple carbon compounds
- Very slow growth rate, doubling time about 18 hours
Why are mycobacteria more resistant to chemical agents than other bacteria?
The hydrophobic nature of their cell surface
What are the types of cultures for mycobacteria?
- Semisynthetic agar media: Middlebrook 7H10, 7H11
- Inspissated egg media: Löwenstein–Jenson
- Broth media: Middlebrook 7H9, 7H12
What are the contents of semisynthetic agar media for mycobacteria?
- Defined salts
- Vitamins
- Cofactors
- Oleic acid
- Albumin
- Catalase
- Glycerol
What are the contents of inspissated egg media for mycobacteria?
- Defined salts
- Glycerol
- Complex organic substances (e.g. fresh eggs/yolks, potato flour)
What are the two types of tuberculosis by manifestation?
- Latent TB (LTBI): asymptomatic, not infectious, present in up to a third of the world’s population
- Tuberculosis disease: fatal without treatment
How is Mycobacterium tuberculosis transmitted?
Aerosols
How are some MTC species other than Mycobacterium tuberculosis transmitted?
Vehicleborne through unpasteurized milk
What is the rule for the distribution of outcomes in those exposed to Mycobacterium tuberculosis?
10/3/1: for every 10 exposed, 3 become latent, 1 becomes active (6 are not infected)
What is the pathogenesis of tuberculosis disease?
- The mycobacteria enter the body via respiratory aerosols
- The droplets evaporate, leaving cells small enough to be deposited in the alveoli
- The host responds by release of cytokines and recruitment of monocytes and macrophages
- Mycobacteria begin to multiply within macrophages. Some macrophages kill the bacterium, others are killed
How does latent tuberculosis infection form?
A granulomatous shell forms around the focus of infection, keeping the cells under control
How do tubercle bacilli spread after infecting the alveoli?
- Upon first infection, the tubercle bacilli always spread from the initial site via the lymphatics to the regional lymph nodes
- The bacilli may spread further by the lymphatics or by the blood (hematogenous/miliary spread)
Where, other than the lungs, can tuberculosis infection be established?
- Pleura
- Lymph nodes
- Pericardium
- Kidney
- Spine
- Brain
- Abdomen
What are the types of tuberculosis disease by pathology?
- Exudative type: an acute inflammatory reaction with edema fluid, neutrophils, and monocytes around the tubercle bacilli, resembling bacterial pneumonia
- Productive (proliferative type): a chronic granulomatous region with a central area of large multinucleated giant cells containing tubercle bacilli, a mid zone of pale epithelioid cells arranged radially, and a peripheral zone of fibroblasts, lymphocytes, and monocytes
Where in the lung does primary infection with Mycobacterium tuberculosis occur?
Any part of the lung, but most often the mid-lung fields or the base
Where in the lung does reactivation infection with Mycobacterium tuberculosis occur?
Almost always at the apex of the lung, where PO2 is highest
What are the clinical manifestations of Mycobacterium tuberculosis infection?
- Fatigue
- Weakness
- Weight loss
- Fever
- Night sweats
- Productive cough and hemoptysis (coughing blood)
- Dyspnea (chest pain and difficulty breathing)
How is Mycobacterium tuberculosis diagnosed in the lab?
- Smears with Ziehl–Neelson stain: low sensitivity
- Cultures: gold standard
- Nucleic acid amplification test
- Tuberculin skin tests
- IFN-γ release assay
How are sputum samples for Mycobacterium tuberculosis diagnosis obtained?
- Coughed up in older children and adults
- Broncheoalveolar lavage (BAL) during bronchoscopy in young children or people with trouble coughing up sputum
What types of culture are used in the diagnosis of Mycobacterium tuberculosis?
- Mainly: Löwenstein–Jenson, M7H10
- Radiometric broth culture (BACTEC system)
- Mycobacterial growth indicator tube (MGIT)
How does the tuberculin skin test work?
- Tests for type IV hypersensitivity to purifed protein derivative (PPD), a TB antigen
- Has low specificity, as it gives a positive result in those vaccinated, exposed to non-tuberculous mycobacteria, and those with latent infection
How does the IFN-γ release assay work?
Monocytes are extracted from the blood and tested to see if they release IFN-γ in response to TB antigen
How is Mycobacterium tuberculosis treated?
Treatment occurs for 6–8 months: 2 months of intensive therapy followed by 4–6 months of lower dose continuation
- Isoniazid (INH)
- Rifampin (rifampicin, RMP)
- Pyrazinamide (PZA)
- Either ethambutol (EMB) or streptomycin (SM)
Which drug is used for preventitive therapy in high risk patients with LTBI?
Isoniazid (INH) for 9 months
How is tuberculosis disease prevented?
- Prompt and effective treatment of patients with active tuberculosis and careul follow-up of their contacts
- Vaccination, particularly with BCG
What are the photochromogens?
- M. kansaii: TB-like
- M. marinum: causes aquarium granuloma in fishtank workers
- M. ulcerans: infects soft tissues
All are slow growers
What are the scotochromogens?
- M. scrofulaceum: causes lymphadenitis (slow grower)
Define
Photochromogen
Producing pigment in light but not in darkness
Define
Scotochromogen
Producing pigment in darkness
Define
Nonchromogen
Don’t produce pigment
What are the nonchromogens?
- M. abscessus
- M. fortuitum group
- M. chelonae group
All are rapid growers and infect soft tissue
What type of mycobacteria are those of the M. avium complex? What disease do they cause?
- Slow-growing nonchromogens
- Cause disseminated or pulmonary infection in imunocompromised patients (particularly AIDS patients) upon expossure to bird dropings with the bacteria
What type of climate is suitable for growing Mycobacterium leprae?
Cooler temperatures (around 30ºC), which is why it preferentially infects the face and extremities
What is the pathology of leprosy?
- Lesions form on the cooler tissue of the body, including the skin, superficial nerves, nose, pharynx, larynx, eyes, and testicles
- Neurologic disturbances occur due to nerve inflitration, resulting in anesthesia, neuritis, paresthesia, trophic ulcers, bone resorption, and shortening of the digits
What are the types of leprosy infection?
- Lepromatous leprosy: course is progressive and malignant with nodular skin lesions, deficient cell-mediated immunity, and skin infiltration with regulatory T cells. Give a negative skin test
- Tuberculoid leprosy: course is benign and nonprogressive, with a small number of macular skin lesions and intact cell-mediated immunity. Give a positive skin test
- All patients start with borderline-LL and proceed to either true LL or TL
How is leprosy diagnosed?
- Scrapings from skin or nasal mucosa or from a biopsy of earlobe skin are smeared for staining with Ziehl–Neelsen stain
- Biopsy of skin or a thickened nerve for histologic analysis
- There are no serologic tests of value
