Determinant of Pathogenicity Flashcards
what are the important stages for pathogens
maintain reservoir, transport/entry into host, adhere and invade cells/tissues, multiply in host, evade host defence, damage host, return to reservoir
what is the definition of pathogenicity
the ability of an organism to cause disease
what is the definition of virulence
the degree of harm caused by a microorganism
what does virulence depend on
infectivity, invasiveness and degree of damage
what are some virulence factors
adhesion, invasion, evasion of host defence, obtaining nutrients from the host, toxicity
what is ID50
infectious dose;
ID50 is dose required to infect 50% of hosts
what is LD50
lethal dose; LD50 is dose required to kill 50% of hosts
what is direct transmission
host-to-host transmission of disease
what is indirect transmission
host-to-host transmission facilitated by living or inanimate objects
what are some direct transmission routes
respiratory, body contact, faecal-oral, body fluids, vertical transmission
what pathogen uses respiratory direct transmission route
myobacterium tuberculosis
what pathogens use body contact direct transmission route
STDs, skin infections, staph.aureus through damaged skin
what pathogens use the faecal-oral route of direct transmission
GIT pathogens like salmonella enterica
what pathogens use the body fluid route of direct transmission
hepatitis, HIV
what pathogens use the vertical direct transmission route
parenteral/perinatal/postnatal
germline (through viral DNA, like certain types of leukemia)
what are some vehicles for indirect transmission
soil, contaminated water, contaminated food, fomites
what are fomites
inanimate objects that act as vehicles for indirect transmission
what are some vectors for indirect transmission
plasmodium, warm-blooded animals, rat flea
what are some portals of entry
skin, mucosal surfaces
what are some bacterial adhesins
proteins, polysaccharides
they help the bacteria adhere to the host’s target site
what are the host factors for adhesion
protein-protein interactions
protein-carbohydrate interactions
receptors like membrane protiens, glycolipids, extracellular matrix proteins (collagen, fibronectin)
how do e.coli cells cause UTIs
P-pili or type 1 pili bind to sugar moieties (globobiose mannose) of glycolipids on epithelial cells lining urinary tract
e.coli bind to epithelial cells in the bladder
what is extracellular invasion
when barriers of tissues are broken down
what is intracellular invasion
when microbes penetrate cells and survive intracellularly
what is meant by vertical transmission routes
from mother to child
what is the flagellum used for
motility in bacterial adhesion
what is the fimbrium used for
attachment/binding during adhesion
where can obligate intracellular bacteria survive
only inside cells
what is an advantage of extracellular invasion
allows access to niches in tissue that aid in proliferation and spreading
how is extracellular invasion achieved
through production of enzymes that attack the extracellular matrix, degrade carbohydrate-protein complexes between cells and disrupt cell surface
what is the action of the hyaluronidase enzyme
hydrolyses hyaluronan
which organisms utilise the hyaluronidase enzyme
streptococci, staphylococci, clostridia
what is the action of the enzyme collagenase
degrades collagen
which organisms utilise the collagenase enzyme
clostridium perfringens
what is the action of the enzyme haemolysin
lyses erythrocytes and other cells
which organisms utilise the enzyme haemolysin
staphylococci, streptococci, e.coli
what is the action of the enzyme streptokinase
digests fibrin clots
which organisms utilise the enzyme streptokinase
staphylococci, streptococci
how do bacteria utilise intracellular invasion
some use it to survive, others use it as a means of proliferation or spreading
what are some methods of intracellular invasion
phagocytic cells invading through phagocytosis
non-phagocytic cells invaded using systems that induce a phagocytosis-like process
what are the five steps of phagocytosis
- phagocyte encounters bacterium that binds to cell membrane
- phagocyte uses cytoskeleton to push its cell membrane around the bacterium, creating a large vesicle (phagosome)
- phagosome containing bacterium separates from the cell membrane and moves into the cytoplasm
- phagosome fuses with lysosomes containing digestive enzymes
- bacterium is killed and digested within the vesicle
what happens to bacteria that survive phagocytosis
they reside in the phagolysosome
they reside in an unfused phagosome
they destroy or escape from the phagosome and live in the cytosol
what happens during invasion of non-phagocytic cells
- bacterial proteins recruit host proteins to induce pagocytosis
similar to gram-negative secretion system used by salmonella or pseudonomas - invasion proteins injected
- activate host signalling and recruit actin
what happens during invasion - extracellular summary
adhered bacterial pathogen combines with proteases and glycanases to extracellularly invade host cells
what happens during invasion - intracellular summary
adhered bacterial pathogen invades host using phagocytosis or induced uptake
intracellular residence in phagolysosome, unfused phagosome or host-cell cytosol
how are biofilms formed
bacteria attach to a surface, grow and become enveloped in a matrix
what is high bacterial density
production of virulence factors through quorum sensing
what is the function of a biofilm
to protect from phagocytosis, antibiotcs and disinfectants
what is the main nutrient that is limiting for bacteria in the host
iron
in aerobic conditions, it is oxidised in ferric form and has low solubility
what proteins include iron complexes and are found in the body
transferrin, lactoferrin, ferritin, haemoglobin
how do bacteria take in iron
direct contact using cell surface proteins
by secreting small compounds (siderophores) with high affinity for iron that capture iron from host proteins or insoluble ferric salts
what cell surface proteins are used in bacterial uptake of iron
transferrin binding protein, haemoglobin binding protein
what are siderophores
they are produced when iron concentration is low, high affinity for iron, compete for free or bound iron, transport iron into cell
what are defence mechanisms used to evade host defence
physical barriers, innate immune system, adaptive immune system
what avoidance strategies are used by bacteria to evade host defence
evade complement, resist phagocytosis, intracellular survival, evade host antibody response
how do bacterial capsules help them evade complement
they have thick polysaccharide layers around the cells which prevents complete activation by host cells
how to LPS O-antigens on bacterial cells help them evade complement
the elongated O chains prevent complement activation
how do bacteria prevent effective contact with phagocytes
using biofilms, capsules or specific proteins
how do bacteria affect phagocyte migration
s. pyogenes peptidase cleaves complement factor C5a
how do bacteria destroy phagocytes
using toxins such as leukocidins
what is a phagolysosome
a phagocyte fused with a lysosome
how do phagocytosed bacteria survive
they prevent formation of phagolysosomes and destroy or escape from the phagosome and live in cytosol
how do bacteria evade the host-antibody response
by binding to host proteins like fibronectin or albumin
this means the body will not detect them as foreign
they also produce surface proteins which bind antibodies ‘backwards’ staph aureus reverses protein A to prevent opsonisation
what is opsonisation
the attachment of antibodies to a foreign body
what is anti-opsonisation
antibodies are bound with the antigen binding site facing outwards, the bacteria is not identified as foreign
what is the body response to bacterial toxins
immediate host damage and induced inflammation
what are exotoxins
actively secreted during growth
what are endotoxins
structural parts of bacteria only released during bacterial lysis
what are toxoids
inactive or low activity and used for vaccinations
how are exotoxins ingested
food poisoning
no adherance/growth/colonisation of the pathogen in the host
how are exotoxins produced
colonised after infection
damage can be local or toxin can spread through blood
what cells do host-sit specific exotoxins target
neurotoxins, enterotoxins, cytotoxin
what do membrane disrupting toxins target
leukicidins, haemolysins, phospholipidases
what do superantigen type exotoxins do
stimulate T cells to release cytokines
how does a pore forming toxin work
exotoxin forms a pore in the cell membrane, an uncontrollable entry of water then causes the cell to lyse
how does bilayer disruption work
phospholipase exotoxin causes disruption of the bilayer which causes cell lysis
what is the effect of superantigens
massive non-specific inflammatory response
leads to epitelial damage, circulatory shock, multi-organ failure
what bacteria produce superantigens
staphalococci and steptacocci
what are features of the lipid A component of LPS in endotoxins
heat stable, only released when bacteria lyse, induces fever, initiates complement and clotting cascades, toxic shock
antibiotic treatment may lead to release of LPS
where are lipid A components of LPS in endotoxins found
in the outer membrane of gram-negative bacteria
what does the bacterial Fur protein regulate
iron
what is the Fur protein response to high levels of iron
repression or ‘switching off’ of genes
what is the Fur protein response to low levels of iron
de-repression or ‘switching on’ of genes
what is a quorum
minimal number of cells before virulence factors are produced
what does quorum sensing involve
two components:
- autoinducer - small diffusable molecule
- R protein - activates transcription of genes when R protein binds to autoinducer; binding only occurs at high concentrations; high concentration of autoinducer only at high cell density
can quorum sensing be effective for biofilms
biofilms have high cell density; biofilm formation often leads to expression of virulence factors through quorum sensing
