Miscellaneous Bacteria

Question 1

obligate intracellular bacteria

Answer 1

can only grow and multiply in eukaryotic cells, not as free-living organisms

facultative - can both grow inside and outside cells

Question 2

Rickettsiaceae

Answer 2

family of small Gram-negtive coccobacilli

strict intracellular pathogens

transmission is often by insect vectors

four genera are medically important - Rickettsia, Coxiella, Ehrlichia, Anaplasma

Question 3

Bartonella spp.

Answer 3

formerly thought to be closely related to the Rickettsiaceae

now classified as distinct from this family

actually facultative intracellular bacteria

two medically important species - B. henselae and B. quintana

cause cat scratch disease and bacillary angiomatosis

Question 4

Coxiella burnetii

Answer 4

cause of Q fever - fever, pulmonary infiltrates, NO rash

harbored by sheep and other animals - especially abundant in the placenta and fetal membranes

spread by aerosols during birth of lambs or other animals or through ingestion of unpasteurized milk

Question 5

Ehrlichia chaffeensis and Anaplasma phagocytophilum

Answer 5

both transmitted by ticks

Ehrlichia infects monocytes and macrophages whereas Anaplasma infects neutrophils

cause similar infections called ehrlichiosis and anaplasmosis - patients present with fever, ehadaches, and myalgias, thrombocytopenia, and leukopenia

Question 6

Chlamydia

Answer 6

three medicall important kinds - C. trachomatis, C. pneumoniae, and C. psittaci

complicated extracellular and intracellular life cycle - elementary body (EB) and reticulate body (RB)

• C. trachomatis* causes sexually transmitted diseases
• C. pnumoniae* and C. psittaci cause pneumonia

Question 7

mycoplasma

Answer 7

NOT obligate intracellular bacteria but are discussed here because they cause disease very similar to that of Chlamydia

smallest organisms that can be free-living in nature and self-replicating

common cause of community-acquired pneumonuia

Question 8

three most important spirochetes

Answer 8

• Borrelia burgdorferi*
• Treponema pallidum*
• Leptospira interrogans*

Question 9

Borrelia

Answer 9

two species are medically improtant:

Borrelia burgdorferi (Lyme disease, tick transmission to humans)

B. recurrentis (relapsing fever, transitted to humans through ticks and lice)

Question 10

Treponema

Answer 10

causes syphilis

Question 11

Leptospira

Answer 11

Leptospira interrogans - aerobic spirochete, causes infections in a variety of animals such as rats, cattle, and dogs

transmitted to humans following exposure to water contaminated with animal urine - ingestion, through cuts in the skin, exposure of conjunctiva

primary phase - fever, chills, headache, and muscle pains as the organism disseminates throughout the bloodstream, symptoms reside after a week as bacteria are cleared from the bloodstream

secondary phase - 1-3 days later recurrence of symptoms, 15% of patients will develop meningitis

effective treatments - tetracycline/doxycycline, penicillin, amoxicillin/ampicillin, erythromycin

Question 12

Mycobacteria

Answer 12

Gram-positive structure but stains acid-fast

60% lipids in cell envelope (mycolic acid)

most grow very slowly

cause chronic disease with insiduous onset

• M. tuberculosis* (TB)
• Mycobacterium bovis* (TB-like disease in humans and cattle)
• M. leprae* (leprosy)

Question 13

Micobacterium tuberculosis

Answer 13

facultative intracellular organism - strictly aerobic, usually only infects humans

causes tuberculosis

Question 14

Micobacterium tuberculosis determinants of pathogenicity

Answer 14

exposure, infection and disease

coughing person with pulmonary tuberculosis gives off aerosolized droplets

bacteria in the aerosol particles are taken up by alveolar macrophages when enhaled, survival and multiplication within macrophages -> infection

organism survives in a phagosome by preventing fusion with lysosome

spreads to local lymph nodes, disseminates to remote sites, eventually controlled but not eradicated by the host immune response

cellular immune response is key, delayed type hypersensitiveity

reactivation occurs in 10% of infected patients, 5% in the first 2 years and 5% during the rest of the person’s life

Question 15

reactivation tuberculosis

Answer 15

most frequently involves the lung, bu tmay occur at any site

reactivation of TB results int he classic signs and symptoms of TB:

fever

night sweats

weight loss

upper lobe pulmonary lesions if reactivation is in the lungs

leads to cough that spreads the organism to the next host

Micobacterium tuberculosis

Question 16

Micobacterium tuberculosis histopathology

Answer 16

cellular immune response - recruitment of mononuclear cells -> amorphous collection of macrophage,s monocytes, and neutrophils

macrophages differentiate in to multinucleated giant cells, foamy macrophages, and epithelioid macrophages

lymphocytes recruited to site -> surrounds macrophages

fibrous layer forms around macrophages -> now called granuloma

dying macrophages release toxic products -> necrosis of the center of the granuloma -> “caseating granuloma”

bacteria survive within the caseous material

granuloma ruptures into airway -> bacteria spilled into the airways -> coughed out into the environment

Question 17

Micobacterium tuberculosis bacterial factors

Answer 17

mycolic acid and liupids - unique cell envelope lipids essential for survivial of the organism in its host

these lipids may alter the host immune response to M. tuberculosis

slow growth (12-24 horu doubleing time) leads to antibiotic resistance

Question 18

Micobacterium tuberculosis clinical disease

Answer 18

chronic disease, two types of disease

pulmonary TB:

chronic productive cough with blood0tinged sputum

cavities or infiltrates are often seen in the apex of the lung

extrapulmonary TB:

disease may occur in other organs and sites

lymph nodes, pleura, genitourinary tract, bones and joints, meninges, and peritoneum

particularly commin in HIV-infected patients

Question 19

Pott’s DIsease

Answer 19

TB of the spine

Question 20

Miliart TB

Answer 20

widely disseminated TB not controlled by the immune system

may follow primary or reactivation tuberculosis

cough may or may not be present

hepatomegaly, splenomegal, and lymphadenopathy are common

frequently, CXR reveals a miliary reticulonodular (snowstorm) pattern

sputum AFB smears are usually negative

skin PPD testis negative in approximately 1/2 of cases

Question 21

Mycobacterium tuberculosis diagnostic tests

Answer 21

tuberculin skin testing

interferon-gamma release assays (IGRAs)

Question 22

Tuberculin skin testing

Answer 22

tuberculin consists of heat-stable proteins liberated into liquid culture media

purified protein derivative (PPD) of tuberculin is used to skin test individuals

PPD is injected intradermally -> eviddence of a delayed-type hypersensitivity reaction (induration) is sought after 48-72 hours

disadvantages - cross-reacts with BCG vaccine, cross-reacts with some atypical mycobacteria, requires follow-up visit to check result

Mycobacterium tuberculosis

Question 23

interferon-gamma release assays (IGRAs

Answer 23

alternative to PPD

patient’s lymphocytes incubated with M. tuberculosis antigens

if patient is infected with M. tuberculosis, lymphocytes will produce interferon-gamma, which is detected by ELISA

does not cross-react with most other Mycobacteria spp. or BCG vaccination

Mycobacterium tuberculosis

Question 24

Gold standard for diagnosis of TB

Answer 24

growth of M. tuberculosis from clinical specimens such as sputum

Lowenstein-Jensen medium (60% homogenzed egg with malachite green to inhibit growth of other bacteria)

growth is very slow - 3-6 weeks of incubation

new system use radio-labeled palmitic acid - metabolized to liberate radio-labeled CO2 -> labeled CO2 can be detected long before colonies are visible

nucleic acid probes - rapidly speciate growing cultures

Mycobacterium tuberculosis

Question 25

staining *Mycobacterium tuberculosis*

Answer 25

lipids in cell wall make these bacteria very hydrophobic resist staining with Gram-stain detect using acid-fast stain (AFB) note that other mycobacteria area also AFB and may be found int he sputum

Question 26

*Mycobacterium tuberculosis* treatment

Answer 26

ioniazid for a total of 9 months to treat infection disease progresses slowly and require multiple drugs long periods of time typical treatment: first two months ioniazid, rifampiun, pyrazinamide, and ethambutol next four months isoniazid and rifampin

Question 27

multiple-drug-resitant (MDR) TB

Answer 27

resistance to rifampin and isoniazid increasingly freqeutn and difficult to treat directly observed therapy (DOT) may treat with 506 drugs for a year or more surgery sometimes beneficial *Mycobacterium tuberculosis*

Question 28

Extensively drug resistant (XDR) TB

Answer 28

MDR-TB with additional resistance to quinolones and at least one 2nd line injectable agent

Question 29

*Mycobacterium tuberculosis prevention*

Answer 29

BCG vaccine - drived from attenuated strain of *M. bovis*, effectiveness is variable respiratory isolation, private room with negative pressure and filtered air patietns with latent TB should be treated to prevent reactivation disease

Question 30

*Mycobacterium leprae*

Answer 30

obligate intracellular pathogen cause of leprosy very slow division times - once every 11-13 days disease of rural poor

Question 31

*Mycobacterium leprae* determinants of pathogenicity

Answer 31

human-to-human transmission dense, inert lipid capsule surrounds organism genome -\> 1/3 fewer genes than *M. tuberculosis* no toxins, organism can directly kill Schwann cells

Question 32

tuberculous leprosy

Answer 32

intense cell-mediated immune response very few bacteria are seen in tissues noncaseating granulomas Th1 response *Mycobacterium leprae*

Question 33

lepromatous leprosy

Answer 33

no cellular immune response many bacteria present Th2 response *Mycobacterium leprae*

Question 34

*Mycobacterium leprae* clinical disease

Answer 34

incubation period of 3-5 years **tuberculous leprosy** * hypopigmented macular skin lesions with raised edges and depressed center * large peripheral nerves become enlarged and may be palpable * ulnar, peroneal, and greater auricular nerves * neuronal dmage leads to muscle atrophy and contractures, especially of the hands and feet * subsequent traumal leads to infections and further damage **lepramatous leprosy** * skin lesions may be of any shape but are usually raised * face, ears, wrist, elbows, buttocks, and knees * later in the skin of the face and forehead becomes thickened and folded * septal perforation and nasal collapse lead to "saddle-nose" * nerve involvement leads to loss of peripheral sensation, which results in trauma and secondary infections **borderline leprosy** * forms of the disease that are between tuberculoid and lepromatous * peripheral tissues are especially affected, perhaps because they are cooler

Question 35

*Mycobacterium leprae* diagnostic laboratory tests

Answer 35

does not grow on artificial media or cell culture cultured in armadillos and on the footbads of mice extremely slow grower, divides once every 11-13 days in the mouse footpad diagnosis is made by histologic examination of a biopsy of a skin lesion

Question 36

*Mycobacterium leprae* treatment

Answer 36

dapsone and rifampin =/- clofazimine 6-12 months

Question 37

*Mycobacterium leprae* prevention

Answer 37

BCG somewhat effective against *M. leprae* contact precautions are not necessary -\> risk of transmission is very low family members and other close contacts should be examined annually for evidence of disease