Mechanisms of Bacterial Pathogenesis Flashcards
Define Koch’s postulates
A microorganism has to:
* Be present in every infection case
* Be cultured from cases in vitro.
* Reproduce disease in an animal.
* Be isolated from the infected animal.
This= not possible for non-culturable organisms e.g. leprosy, syphilis
* What about food poisoning – B. cereus and toxins, no infection with organism, but disease
What are the types of infection?
Give the stages of infection
Which factors of a microbe can increase its virulence?
Adherence: to mucosal sites using pili
Invasion: surface features, secreted effector proteins
Capsules: polysacs protect opsonization and phagocytosis.
Endotoxins and Exotoxins
Siderophores: iron-binding factors to compete w the host for iron Hb, transferrin, and lactoferrin
Describe the pathogenesis of whooping cough, cholera, meningitidis, staph A, tb and strep pneumo
Bordetella pertussis: non-invasive, produces 10-12 exotoxins allows bacterium to survive as a surface-dwelling
Vibrio cholerae: non-invasive enteritis - effect on ion transport
Neisseria meningitidis: nasopharynx carriage, endotoxins, bacteraemia
Staph aureus: locally invasive and exotoxins
Mtb: invasive, polysaccharide capsule = preventing digestion, granuloma immunopathology
Strep pneumoniae: capsule w/ teichoic acid = evade immune system = inflammation + toxin (pneumolysin), carriage nasopharynx, can become invasive
Bacterial Toxins cause damage to cells, tissues or the whole host organism, thereby contributing to disease
What are the types of bacterial toxins and where is their site of action?
Give the functions of toxins in infection
Hyaluronidase, collagenases, lethicinases etc promote adhesion, survival or spread of bacteria
Damage or destroy cells
Interfere with cell metabolism, eg cholera; diphtheria
Affect nerves, eg neurotoxin in botulism and tetanus
There are 3 types of bacterial toxins.
Describe type one toxin- what do they stimulate, give examples
What type of toxin do the superantigens release?
Type one toxin stimulates signalling proteins, GC which changes intracellular CGMP to cause fluid secretion of the host cell (water loss).
E.g. E. coli in ST enterotoxin causes travellers diarrhoea.
Super antigens:
S aureus TSST: toxic shock syndrome toxin
S. pyogenes: erythrogenic toxin = scarlet fever
Describe the type 2 toxin
Toxins called lysins form pores and damage cell membrane
E.g. S. aureus alpha toxin forms a heptamer pore, damages cell membrane, disrupts ion transport = lysis
Clostridium perfingens: gram+ rod, anaerobe, spore forming
Produces multiple toxins, alpha-lecithinases, phospholipase C, which kills RBCs and WBCs
A disease associated with type two toxin is necrotising fasciitis.
Explain its virulence determinants.
Necrotising fasciitis: caused by S. pyogenes (group A Strep, beta haemolytic)
Cysteine protease SpeB degrades skin
M proteins and LTA = adhesins
Strep pyrogenic exotoxins (SPEs) A, B and C = toxins
Hyaluronic acid capsule blocks opsonisation = protection
Streptolysin forms pores to kill cells
Describe type three bacterial toxin
Type 3:intracellular action after translocation of an active subunit
Classified by enzymatic action:
ADP-ribosylation: cholera, diphtheria
N-glycosidase: shigella, EHEC O157:H7
Glucosyl transferase: C. diff
Zn2+: endopeptidase: botulism, tetanus
Also classified by molecular target/effect:
G and rho proteins for cell signalling
EF2 and rRNA for protein synthesis
Actin for cellular dynamics and trafficking
Which toxins inhibit protein synthesis?
Shigella causes dysentery, releases the Shiga toxin which cleaves adenosine from RNA, preventing ps
C. diphtheriae causes diphtheria where ADP ribosylates EF2
Some bacteria have the ability to directly inject exotoxins into host cells. What can these do?
Some bacteria have the ability to directly inject exotoxins into host cells. They can:
-Form pores in host cell membrane
Cleave surface molecules on the host cells, impairing their normal signaling.
Bind to specific receptors on host cells, affecting signal transmission, or enter cell via endocytosis (receptor mediated)
Describe diphtheria
Occurs in the pharynx, non-invasive multiplication.
Toxin produced locally.
Absorbed by lymph to give systemic effects such as fever, pallor, weakness, polyneuritis and myocarditis
Kills epithelial cells and polymorphs = ulcers, pseudomembrane, inflammation, bull neck, resp obstruction
Explain the mechanism of travellers diarrhoea
Diarrhoea: Heat stable toxin changes guanylate signalling which damages intracellular signalling
This causes a loss of Cl and fluids= diarrhoea
Cholera toxin works in similar way = water loss
Describe tetanus
Clostridium tetani secretes toxin Zn2+ endopeptidase for synaptobrevin
Tetanospasmin toxin blocks release of inhibitory GABA and glycine = spastic paralysis
What is floppy baby syndrome?
Infantile botulism/floppy baby syndrome:
Clostridium botulinum
Also produces Zn2+ endopeptidase for synaptobrevin but acts at neuromuscular junction
This prevents Ach release, causing flaccid paralysis
What does this show?
Inflammation due to a pyogenic infection. A pyogenic infection is an infection that causes mucho pus, eg staphylococci, streptococci and meningococci
Why is this CT concerning?
It shows severe infection of the muscle compartment (left). Often muscle infection leads to compartment syndrome as muscles, unlike skin, cannot expand/swell when infected bc the fascia prevents it.
This leads to very high pa and can even cut off blood supply, leading to necrosis
Describe the bacterial enzymes other than the typical protease/lipase/nuclease etc
Hyaluronidase which breaks down Hyal Acid
Origin: Streptococci e.g. Strep pyogenes
Result: Disruption of tissue mosaic allowing bacteria and inflammatory exudate to spread
Alpha-lecithinase which splits lecithin – found on many cell surfaces. Causes major tissue damage
Source: Clostridium perfringens
