Acid-Fast, Filamentous, Wall-Less Bacteria

Front 1

List all the atypical bacteria:

Back 1

Front 2

Key points about Mycobacteria:

Back 2

*Slim “atypical” rods
*Nonmotile and nonspore forming
*Obligate aerobes; many species are slow-growers
*Cell wall is complex and contains long-chain fatty acids called mycolic acids and lipoarabinomannan (LAM), a lipid polysaccharide complex extending from the plasma membrane to the surface.
*Acid-fastness = hallmark of Mycobacteria.

Front 3

Back 3

MYCOBACTERIA

Front 4

Describe the acid-fastness of Mycobacteria:

Describe the Cord factor:

Back 4

*Cannot take up stains; can be stained with Carbol Fuchsin, followed by decolorization with 3% HCL in 70% alcohol. Other organisms would be decolorized but not Mycobacteria. ACID-FAST!

*Cord factor (trehalose dimycolate) is correlated with virulence of the organism! Inhibits IFN-g (less macrophage activation)

Front 5

Describe the CW of mycobacteria:

Back 5

*Complex, glycolipid cell wall
*Mycolic acids linked to arabinogalactan
*Lipoarabinomannan (LAM): induces cytokine production
*Together, these and additional cell surface proteins are antigenic. Extracted and partially purified preparations of these protein derivatives (PPDs) are used as skin test reagents to measure exposure to M. tuberculosis.

Front 6

Back 6

*Corded growth in mycobacteria.

Front 7

Back 7

mycobacteria

Front 8

List clinically relevant mycobacterium species:

Back 8

*only Runyon IV are fast-growers
*Runyon I are pigmented yellow
*Main focus is on TB
*Avium is associated with HIV

Front 9

Back 9

*M. tuberculosis colonies on Lowenstein-Jensen agar after 8 weeks of incubation.
*Agar contains homogenized egg in nutrient base with dyes to inhibit the growth of nonmycobacterial contaminants.

Front 10

Pathogenesis of M. TB:

Back 10

*Mycobacteria include a wide range of species pathogenic for humans and animals.
*M. tuberculosis is a STRICT HUMAN pathogen.
*Most nonpathogenic species are widely distributed in the environment. Diseases caused by mycobacteria usually develop slowly, follow a chronic course, and elicit a GRANULOMATOUS response.
*Mycobacteria lack classic exotoxins and endotoxins!!!! Disease is related to host immune response (DTH and cell-mediated immunity).

Front 11

HOW IS TB SPREAD???

Back 11

*Spread via aerosol droplet nuclei from patients with active pulmonary TB.
*Brief encounters pose limited risk; usually repeated or prolonged contact is required for transmission.
*Initial multiplication is in the alveoli with spread through lymphatic drainage to the hilar lymph nodes.
*Lymphatic drainage to the bloodstream can spread organisms throughout the body.

Front 12

What happens with TB once it reaches the alveoli?

Back 12

*Once in alveoli, the organism gets ingested by macrophages.
*Instead of being killed, M. tuberculosis survives as an intracellular pathogen by blocking acidification of phagosome and phagolysosome formation.
*Ingested bacteria multiply in the macrophage.

Front 13

What does our immune system do once TB gets into the alveoli?

Back 13

*Th1 cellular immune responses attempt to activate the macrophage by secreting cytokines. If successful, the disease is arrested.
*Inflammatory elements of DTH are attracted and cause destruction.
*If activation is not successful, disease and injury continue. If the Th1 process is effective, the source of DTH stimulation wanes and the disease resolves.
*Success depends on size of the inoculum. If dose is too large, you get remaining dormant infections.

Front 14

Back 14

The response to TB manifests in the formation of a granuloma.

Front 15

Back 15

DTH in response to TB leads to caseous necrosis in the center of the lesion. Visible in x-rays.

Front 16

Describe dormant TB reactivation:

Back 16

*Dormant TB reactivation typically starts in the upper lobes of the lung (more oxygen up there) with granuloma formation.
*DTH-mediated destruction can form a cavity, which allows the organisms to be coughed up to infect another person.
*Have to immune compromised for this to happen (aging for example).

Front 17

Back 17

Chest radiographs of (a) primary tuberculosis, showing the Ghon focus in the lower left lung, and (b) post-primary pulmonary tuberculosis showing advanced disease.

Front 18

Back 18

*miliary TB--it has seeded entire lung. Can occur with severe immune compromise like HIV.

Front 19

Overview picture of TB pathology:

Back 19

*several scenarios for reactivation

Front 20

Key points about M. avium-intracellulare complex (MAC):

Back 20

*Frequently recovered from soil and water
*Some cause TB in birds but do not infect humans; whereas others infect a variety of mammals including humans.
*Both species produce disease in immunocompromised individuals.
*M. avium is the most common opportunistic bacterial infection seen in late AIDS patients.

Front 21

Back 21

M. avium-intracellulare complex (MAC)

Front 22

Key points about Mycobacterium leprae:

Back 22

*Cannot be cultured; grows only in armadillos
*Obligate intracellular parasite of macrophages and Schwann cells
*Prolonged exposure with a household contact, i.e. from exudates of skin lesions from a leprosy patient, is required to become infected.
*The incubation period for leprosy is 5-7 years; clinical disease may develop several years after initial contact with organism.
*Rare in U.S.; wider problem worldwide where about 10-12 million are infected (India, China, Brazil, Nigeria); in U.S. most often seen in immigrants from endemic areas.

Front 23

Damage and Disease from m. leprae:

Back 23

*Leprosy (Hansen’s Disease) is a chronic granulomatous condition of the peripheral nerves and mucocutaneous tissues, particularly the nasal mucosa.

*The disease occurs in two major forms with a spectrum of illness in between:
 -Tuberculoid form: few M. leprae are seen in lesions, which are granulomatous with extensive epithelioid cells, giant cells, and lymphocytic infiltration; skin and nerve involvement.
-Lepromatous form: the cellular response is minimal, and growth of M leprae is thus relatively unimpeded. Lesions are infiltrative and diffuse.
*Success of immune response determines which form.

Front 24

Back 24

Mycobacterium leprae. Acid-fast stains of skin biopsies from patients with (A) tuberculoid leprosy, (B) borderline tuberculoid leprosy, (C) borderline lepromatous leprosy, and (D) lepromatous leprosy. Note that there is a progressive increase in bacteria going from the tuberculoid form to the lepromatous form of the disease.

Front 25

Back 25

Mycobacterium leprae. Leprosy lesions.

Front 26

Key points about Actinomyces:

Back 26

*Slow-growing anaerobic branching Gram-positive rods.
*Part of normal flora of oral cavity.
*Most infections due to Actinomyces israelii.
*After local trauma such as a broken jaw or dental extraction, it may invade tissues forming filaments surrounded by areas of inflammation.
*In pus and tissues, the most characteristic form is the sulfur granule.
*Lesions typically involve face and neck.

Front 27

Back 27

actinomyces - sulfur granules

Front 28

Key points about Mycoplasma:

Back 28

*Lack a cell wall.
*They are bounded by a single triple-layered membrane that contains sterols.
*They are highly plastic and pleomorphic and may appear as coccoid bodies, filaments, and large multinucleoid forms.
*Numerous Mycoplasma species have been isolated from animals and humans, but only two species have been significantly associated with human disease:
-Mycoplasma pneumonia: a lower respiratory tract pathogen.
-Mycoplasma genitalium: causes genitourinary tract infections.

Front 29

Back 29

mycoplasma