illustrations of bacterial pathogenicity - respiratory tract

Question 1

what causes diphtheria?

Answer 1

a gram positive rod Corynebacterium diphtheriae
an extracellular toxinogenic bacterium
- an effective toxoid vaccination is used.

Question 2

how is the diphtheria toxin (DTX) controlled?

Answer 2

carried on a bacteriophage integrated into the bacterial chromosome.
- controlled by the TF DtxR, suppresses expression when bound by iron. hence DTX produced in host as iron is low.

Question 3

pathogenesis of diphtheria?

Answer 3

• colonisation of the nasopharyngeal epithelium
• secretes AB type toxin.
• intense local inflammation, mucosal cell damage, bacteria growth in inflammatory exudate.
• pseudomembrane formation, occludes airway and asphyxiates
• toxin can also cause irregular heartbeat, coma and death

Question 4

how does the DTX work?

Answer 4

B part of AB binds HEGF (heparin- binding epidermal growth factor)

• toxin endocytosed. endosome acidified and disulphide bridge between A and B breaks.
• B forms a pore and the A part is released into the cell.
• A will ADP-ribosylate translation elongation factor-2 (EF-2) and block protein synthesis

Question 5

what causes pharyngitis?

Answer 5

streptococcus pyogenes - a gram positive cocci of Lancefield group A.
- haemolytic due to production of streptolysin
- pyogenic (pus forming) that causes other acute suppurative infections (pus forming) such as tonsillitis, scarlet fever, puerperal fever, erysipelas, impetigo and in animals mastitis.
the last 3 can also be caused by staphylococcus aureus

Question 6

what’s impetigo (well, the most common form)?

Answer 6

Impetigo contagiosa - This common form of impetigo, also called nonbullous impetigo, most often begins as a red sore near the nose or mouth which soon breaks, leaking pus or fluid, and forms a honey-colored scab, followed by a red mark which heals without leaving a scar. Sores are not painful, but may be itchy. Lymph nodes in the affected area may be swollen, but fever is rare. Touching or scratching the sores may easily spread the infection to other parts of the body

Question 7

what’s erysipelas?

Answer 7

an acute streptococcus bacterial infection[2] of the upper dermis and superficial lymphatics

Question 8

streptococci and staphylococci are?

Answer 8

both often called pyogenic cocci. staph aureus in particular causes opportunistic infections ie hospital acquired MRSA

Question 9

how does streptococcus pyogenes colonise?

Answer 9

numerous adhesins. colonises throat epithelium

Question 10

streptococcus pyogenes methods of spread, survival and damage?

Answer 10

1 - capsule - poorly immunogenic
2 - surface M protein - antigenic variation and binds complement
3 - C5a peptidase - inhibits chemotaxis
4 - streptolysins O and S - pore forming toxins (beta haemolysis)
5 - pyogenic toxins - superantigens (toxin shock syndrome)
6 - hyaluronidase - breaks down tissue
7 - streptokinase - lyses clots
8 - DNAse - depolymerises DNA in pus to reduce viscosity

Question 11

later complicatind toxic shock like syndrome ons of strep pyogenes infection?

Answer 11

1 - rheumatic fever - heart, joint grnulomas plus fever, may caused rheumatic heart disease
2 - glomerulonephritis - type 3 hypersensitivity - AbAg complexes lodge in glomeruli
3 - necrotizing fasciitis and toxic shock like syndrome (multiorgan failure similar to LPS endotoxin)

Question 12

what causes toxic shock syndrome?

Answer 12

staphylococcus aureus. superantigen cause. similar to strep pyogenes. secreted at site of colonisation and gets into the blood

Question 13

what causes pneumonia?

Answer 13

an inflammatory disease often caused by strep pneumoniae

- most common cause of community acquired pneumonia

Question 14

strep pneumoniae colonizaton?

Answer 14

adhesins for nasopharmynx, resists removal by pneumolysin (a pore ofrming toxin) that damages ciliated cells. IgA protease

Question 15

strep pneumoniae migration?

Answer 15

to lower respiratory tract. avoids phagocytosis wit pneumolysin and its capsule. capsule prevents opsonisation and aids survival in droplets during dissemination.

Question 16

strep pneumoniae damages?

Answer 16

lung tissue with pneumolysin primarily and also some inflammation.

Question 17

legionaire’s disease?

Answer 17

first identified in 1976 at convention of US legion of veterans.
- typically contracted from aircon units ie a point source not propagated. any device that makes a fine mist of water droplets ie water cooler or shower head.

Question 18

legionaire’s disease caused by ?

Answer 18

legionella pneumophila. multiples in alveolar macrophages. prevents phagosome-lysosome fusion.
stimulates cytokine release and lung damage appears to reflect a vigorous inflammatory response.
- a facultative intracellular parasite of amoebae. perhaps how it survives.

Question 19

cause of whooping cough?

Answer 19

bordatella pertussis. acute severe disease in young children.
- diphtheria/pertussis/tetanus vaccine is effective. outbreaks due to vaccine drop. kills over 200,000 pa in the developing world.

Question 20

colonisation of whooping cough?

Answer 20

aerosol inhalation. adhesins to respiratory epithelium (pili, pertactin, filamentous haemagglutinin (FHA)) multiplies in the mucosa.

Question 21

whooping cough damage?

Answer 21

destroy ciliated epithelia and mucosal cells by LPS lipid A acute inflammation. plus an array of exotoxins such as pertussis toxin (adp-ribosylator) and an adenylate cyclase toxin.

Question 22

pathogenesis of whooping cough?

Answer 22

accumilation of mucous, inflammatory cells, dead epithelia and bacteria in the airway.

• fever and bronchitis.
• this and possible toxin action on neurones promotes paroxysms of coughing. life threatening in infants with underlying cardiac/pummonary disease and can lead to neurological sequelas.

Question 23

cause of pneumonic plague?

Answer 23

yersinia pestis. highly virulent with death of around 50% of some cities in 14th century.
over half die in 10 days. death rate closse to 100%. spreads rat to human via fleas to give bubonic plague which spreads via lymphatics (huge nodes) blood to the lungs to give pneumonic pague. can then be exhaled in droplets causing rapid person to person spread.
- necrotic lesions ie of fingers may hvae given the name “the black death”.

Question 24

virulence factors of yersinia pestis?

Answer 24

antiphagocytic capsule, protein toxins inc injected effector proteins that subvert macrophage function. also LPS lipid A as gram negative.

Question 25

cause of meningitis?

Answer 25

several bacteria. some colonise the nasopharynx asymptomatically.

• nisseria meningitidis can colonize 10% of the pop. endothelial damage, cross BBB. inflam of meninges by LPS lipid A. test with lumbar puncture.
• raise ICP cause reduced blood flow and brain damage or death.

Question 26

name four pathogens that can cause meningitis

Answer 26

1 - neisseria meningitidis - gram -ve coccus
2 - haemopilus influnezae type B (Hib) - gram -ve rod
3 - streptococcus pneumoniae - gram +ve coccus
4 - e.coli (neonatal) - gram -ve rod

Question 27

host mimicry?

Answer 27

E.coli K1 and some neisseria meningitidis have sialic acid capsules - host mimicry as its present in most tissues. weakly immunogenic. antibodies for some serotypes.

Question 28

what is pseudomonas aeruginosa

Answer 28

gram -ve bacterium
opportunistic - causes many infections ie burns, wounds, eye, respiratory in cystic fibrosis.
copiously produces an alginate polysaccharide “slime”
direct and indirect damage
forms biofilms. often multidrug resistant by drug efflux pumps

Question 29

cause of TB?

Answer 29

mycobacterium tuberculosis
non motile obligate aerobe, grows slowly.
acid fast as difficult to destain due to waxy impermeable cell envelope of mycolic acid.also makes it resistant to drying and disinfectants and immune attack.

Question 30

how does TB spread and survive

Answer 30

small droplets. ingested by alveolar macrophages.
resist intracellular killing by a number of potential mechs, ie inhibit phagosome lysosome fusion by subversive enzymes.
multiplies in macrophages, disseminate via lymphatics and macrophages lyse to provide new locus of infection.

Question 31

how does the immune system get rid of m. tuberculosis?

Answer 31

Th1 cells sensitised to it activate macrophages, predom via IFNgamma.
increased killing.
TFNalpha and NO secretion.
cell mediated immunity
CD4+ T cell activity is the basis of the tuberculin skin test with mycobacterial protein.
persistent infection often results in shift to TH2 as well as TH1

Question 32

response to persistent m. tuberculosis infection?

Answer 32

type 4 granulomatous inflammation. aggregates of activated macrophages (may diff to epitheliod cells/ multinucleate giant cells), surrounded by fibroblasts and some lymphocytes to wall off. granuloma

Question 33

features of a granuloma?

Answer 33

necrosis, repair (fibrosis and scarring), and inflammation.
intense activation often causes conc release of lytic enzymes causing cheese-like centre.
caseous necrosis which aids spread of bacterium. = miliary TB

Question 34

clinical outcome of TB?

Answer 34

complex balance of bac survival, immune protection and tissue destruction.
determined by host immune status and TB strain virulence.
about 15% of new infections are HIV positive