Additional examples of bacterial disease Flashcards
Diseases arising from colonisation of the respiratory tract
a) pneumonic plague
b) pneumonia
a) Caused by Yersinia pestis. Infecting bacteria spread through lymphatics, lymph nodes enlarge (buboes). Hemorrhagic inflammation, spread to blood, lungs (pneumonic plague), meningitis, septicaemia, multi-organ failure. Necrotic lesions gave name ‘black death’. Virulence factors include an antiphagocytic capsule and protein toxins, including injected effector proteins called Yops that subvert macrophage function to prevent engulfment. Additional inflammatory damage caused by LPS lipid A.
b) Most often caused by Streptococcus pneumoniae. Colonises nasopharynx by adhesins. Resists removal by mucous and ciliated cells by pneumolysin (pore-forming toxin) and IgA protease (host factors to colonisation - alcoholism, viral respiratory infection). Migrates to lower respiratory tract. Avoids phagocytosis by alveolar macrophages: pneumolysin and polysaccharide (carbohydrate capsule). Capsule prevents opsonisation and aids survival in droplets during dissemination. Lung damage then occurs by pneumolysin and inflammation
Diseases arising from colonisation of the respiratory tract: whooping cough
Caused by Bordetella pertussis. DPT (diphtheria-pertussis-tetanus) vaccine is effective, but outbreaks returned when vaccine take-up dropped.
Aerosol inhalation. Colonisation of respiratory epithelium, aided by adhesins. Bacteria multiply in mucosa. Damage to ciliated epithelial cells and mucosal cells LPS lipid A (triggers acute inflammation) and exotoxins including pertussin toxin and an adenylate cyclase. Accumulation of mucus, inflammatory cells, dead epithelial cells and bacteria in the airway. Fever, bronchitis. This and toxin action on neurons promotes paroxysms of coughing. Life-threatening in infants with underlying disease can lead to neurological sequelae
Diseases of the respiratory tract: tuberculosis
Caused by Mycobacterium tuberculosis and closely related to M. bovis. Non-motile obligate aerobe that grows slowly. Acid-fast as difficult to destain due to waxy impermeanle cell envelope (mycolic acid) that makes pathogen resistant to drying and disinfectants, and protects it from innume attack.
Spread by small droplets and are ingested by alveolar macrophages. Virulent strains resist killing by establishing a safe uptake pathway, arresting trafficking and inhibiting phagosome-lysosome fusion (phagosome maturation). Multiply in macrophages, and when they lyse, bacteria can cross alveolar epithelium, enter lymphatics, drain to regional lymph nodes and may enter the blood disseminate aroung the body. New foci of infection.
Lysis of host cells and dissemination is facillitated by the small secreted ESAT6 protein, thought to interact with macrophage membranes and interfere with signalling pathways that down-regulate production of ROS.
In persisting infection, there is immunological shift as CD4+ Th2 cells are produces in additon to protective Th1 cells. Usually, M. tuberculosis-sensitised Th1 cells activate macrophages, predominatly via IFNγ. Increased killing follows (bacteria are phagocytosed, productive phagosome-lysosome fusion) TNFα secretion, and production of NO. Cell-mediated immunity is established. CD4+ T cell activity is basis of tuberculin skin test is Mycobacterial protein.
Response to persisting M. tuberculosis leads to type IV granulomatous inflammation in which aggregates of macrophages (may differentiate to epithelioid cells or multi-nucleate giant cells), surrounded by fibroblasts and a few lymphocytes, wall off the pathogen. Granulomas show ongoing tissue destruction (necrosis), repair (fibrosis, scarring) and inflammation. The intense activation often results in concentrated release of lytic enzymes and leads to caseous necrosis, which aids spread of bacterium (miliary TB)
Diseases of the gastrointestinal tract - food intoxications
a) Clostridium botulinum
b) Staphylococcus aureus
c) Clostridium perfringens
(the ‘poisonings’ are caused without colonisation of the host, so symptoms are seen after a few hours)
a) produces botulinum toxin (BoNT) during anaerobic growth in food (home-canned). Toxin absorbed from stomach. BoNT is protease that cleaves synaptobrevin, a neuronal SNARE. BoNT acts at NMJ, preventing exocytosis of stimulatory neurotransmitter ACh, causing flaccid paralysis. Rare, but life-threatening
b) grows in custard, processed meats at room temp (contamination from human carrier). Stable enterotoxins interact with gastric mucosa and act as superantigens. Bacteria are ingested but don’t colonise
c) germinates from spores that survive in pre-heated foods (meat products, anaerobic). Ingested and produces toxins in the intestine. Toxins interact with mucisa, may be superantigens
Diseases of the gastrointestinal tract: Salmonellosis
Food-borne gastroenteritis caused by Salmonella enterica (raw chicken and eggs).
Salmonella induce host cytoskeletal rearrangement (requires SPI-1-encoded needle and effectors, actin binding SipA, SipC) and forces entry directly via the apical surface of epithelial cells of distal ileum and proximal colon. Salmonella remain within a membrane-bound vacuole, a replicative niche, and multiply. Released from epithelial cells by lysis and induces inflammation (principally via LPS lipid A). Causes gastroenteritis. It is taken up by macrophages and replicates. Survives intracellulary by switching on SPI-2 genes encoding effectors that inhibit maturation of the phagolysosome and confer resistance to defensins and oxidative bursts (pumps, superoxide dimutase, catalase). Inflammatory disease is confined to GI tract. Host response activates cAMP production and fluid secretion, resulting in diarrhoea.
Human host adapted S. typhi causes systemic typhoid fever in the developing world. It replicates in macrophages and is spread systemically via the blood stream to liver and spleen. Severe symptoms caused by typhoid toxin (CDT) and response to LPS lipid A. Bacteria are shed in bile, returning to the intestine and environment.
Diseases of the gastrointestinal tract: diarrhoeal diseases caused by E. coli
a) ETEC
b) EPEC
c) EHEC
a) (enterotoxinogenic) colonises by fimbrial pili adhesins and produces a cholera-like enterotoxin LT. Common cause of diarrhoea in children of developing countries and travellers’ diarrhoea. Spread by contaminated water. Important disease of animals (especially piglets), same toxin, different adhesins provide host tropism
b) (enteropathogenic) initially attach by pilus adhesin. Delivers effectors, including its own receptor Tir, which binds intimin on EPEC surface, into the target cell to facilitate tight adhesion by cytoskeletal rearrangement. Generates pedestals. Inflammation
c) (enterohaemorrhagic) attach by pili and pedestal like EPEC. Inflammation accentueated by Shiga-like toxin SLT, which can also casue renal failure. One predominant serotype is O157, commonly found in beef
Diseases of the gastrointestinal tract: Campylobacter, Listeria, Shigella
Campylobacter - behaves in ways analogous to Salmonella
Listeria - from unpasteurised cheese and salads, can invade and become systemic. Can cross the placenta (endangering the foetus), and the blood brain barrier (meningitis). It is predominantly dangerous to the immunocompromised
Shigella - causes bacterial dysentry, a highly infectious disease characterised by acute inflammation of the colon and low-volume diarrhoea containing blood, mucus and PMNs. Damage is caused directly (by shiga toxin) and indirectly by inflammatory response
