Mycobacterium

Question 1

Mycobacterium general properties

Answer 1

-Slim, poorly staining bacilli -Demonstrate positive acid-fast test. -Nonmotile, obligate aerobes that do not form spores

Question 2

cell wall

Answer 2

-Unusually high lipid content (>60% cell wall mass) -Get very thick and waxy cell walls, which contribute to intrinsic resistance to the host and antibodies -Cannot be gram stained -Stain pink under acid fast staining -Peptidoglycan is covalently linked to other lipid layers -Many branched-chain polysaccharides, proteins, and lipids -Porins and other proteins are found throughout -Mycolic acids: long-chain fatty acids -Lipoarabinomannan (LAM) (similiar to lipopolysaccharide)

Question 3

Growth

Answer 3

-Mycobacteria grow more slowly than most human pathogenic bacteria because of their hydrophobic cell surface, which causes them to clump and limits permeability of nutrients into the cell.  -The most important pathogen, M tuberculosis , shows enhanced growth in 10% carbon dioxide and at a relatively low pH (6.5-6.8)

Question 4

Disease

Answer 4

-Diseases caused by mycobacteria usually develop slowly, follow a chronic course, and elicit a granulomatous response. -Infectivity of pathogenic species is high, but virulence for healthy humans is moderate. -Disease following infection with M. tuberculosis  is the exception rather than the rule.

Question 5

Toxins associated with Mycobacterium

Answer 5

Mycobacteria do not produce classic exotoxins or endotoxins although a protein called early secreted antigenic target (ESAT-6) causes cytolysis and is associated with virulence.

Question 6

Tuberculosis global health statistics

Answer 6

-Roughly one third of world population infected -9 million new cases reported annually -2 million deaths annually 

Question 7

Diagnosis of Tb

Answer 7

-Because of its hydrophobic lipid surface, MTB is unusually resistant to drying, to most common disinfectants, and to acids and alkalis. -TST, Chect X-Ray, Sputum sample (acid fast test), -Definitive diagnosis with culture or nucleic acids test -Skin test: A PPD is used for skin testing for hypersensitivity and is standardized in tuberculin units according to skin test activity >>> Antibody response

Question 8

PPD

Answer 8

purified protein derivative of tuberculin

Question 9

treatment of Tb

Answer 9

-first line antibiotics -second line antibiotics

Question 10

First line antibiotics in treatment of Tb

Answer 10

isoniazid (INH) rifampin (RIF) Ethambutol (EMB) Pyrazinamide (PZA)

Question 11

Second line antibiotics in treatment of Tb

Answer 11

Streptomycin Fluoroquinones Kanamycin Amikacin or Capreomycin Ethionamide or Prothionamide Ether cycloserine or p-aminosalicylic acid (PAS)

Question 12

MDR-TB stands for?

Answer 12

Multidrug Resistant Tuberculosis

Question 13

MDR-Tb main features

Answer 13

-Resistant to more than one anti-TB drug and at least isoniazid (INH) and rifampin (RIF) -Acquired point mutations -Genetic testing of strain allows for better understanding of resistance strains and if performed early allows one to choose the most appropriate drug for primary treatment

Question 14

When does MDR-Tb occur?

Answer 14

-Patient is non compliant with treatment regimen -Patient is not treated with the appropriate drug regimen

Question 15

Tuberculosis pathogenesis

Answer 15

Question 16

Tb mechanism

Answer 16

• TB success depends on avoiding the killing mechanism of phagocytes
• MTb infects and multiplies within host macrophage
• With the development of an acquired immune response, and the arrival of lymphocytes, a granuloma forms
• Human granulomas possess an organized, stratified structure. The macrophage rich center becomes surrounded by a mantle of lymphocytes that may be enclosed within a fibrous cuff that marks the periphery of the structure
• The bacterium is able to persist in a largely inactive or latent form
• In immunocompromised hosts, the granuloma structure is not maintained and the infection can reactivate into active disease.

Question 17

Tbs mechanism within a macrophage

Answer 17

TB survives by arresting macrophage maturation

Fate of bacterium depends on the route of entry

Question 18

Host susceptibility factors for Tb

Answer 18

90% of infections do not result in active disease

Acquired Immunodeficiency

Diabetes, COPD, Smoking

Genetic Coorelates (CGD - chronic granulomatous disease)

Question 19

Vaccines for Tb

Answer 19

M.Bovis BCG Vaccine is the only current option

Not very effective, but is used in high incidence areas

BCG is attenuated, perhaps too attenuated