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1.19.2.11 - Bacteria-Host Infections, BOTH CAUSE MOBIDITY/MORTALITY, Both…
1.19.2.11 - Bacteria-Host Infections
Balance of health and disease
Innate immune response cannot be too great or too small, difficult balancing act and can go wrong
Harmless Environmental material: Allergies (fleas, dust mites)
Commensals, symbiotic bacteria: Food Incompatibilities (milk)
Own material: Autoimmune disease, eg. diabetes
Pathogens
abscess, systemic disease
toxic shock syndrome (immune response too great)
Host- Pathogen Interactions
Contact between host and pathogen
Recognition by host causes immune response
can cause immunopathology (collateral damage)
Pathogen produces virulence factors (delicate balance with the immune response)
Attachment/invasion/ toxins cause damage
Steps in infection and disease process post transmission to host
Invasion- intra/extracellular survival
Subversion of host defence
Adhesion
Replication
Long term survival in host
Spread to further hosts
Role of virulence genes in bacterial pathogens
Virulence factors
Molecules that allow bacteria to adhere, invade, evade host defence, cause tissue damage, replicate or persist in the host
Virulence gene
gene encoding a virulence factor
How have virulence genes evolved
horizontal transfer of virulence genes leading to rapid evolution via
transposons
pieces of DNA within the bacteria that are mobile can move in and out of the chromosome- can also move between chromosomes and plasmids
phage transduction
Phages- viruses that can infect bacteria, some will in addition to packaging their own dna will also randomly include some of the bacterial dna- if these include virulence genes- they can be transmitted to other bacteria
plasmids
can be exchanged with other bacteria
Steps in bacterial infection process
Adhesion
To:
Secretory products (eg. mucus)
Structural components (eg teeth)
cells (ie respiratory tract epithelium)
other bacteria (biofilms eg plaque)
main structures
Fimbrae/ pili ( most frequent structure in gram neg. bact.
adhesive macromolecules embedded in membrane
other structures
flagellum
proteinaecious fibrils
capsules (although on some bact. these prevent adherance
bacteria may produce series of adhesive structures either concurrently or consecutively
How adhesion affects bacteria
Inhibition/stimulation of growth
Induction of more adhesive structures- allows tighter interactions between bact. and host cell
Upregulation of siderophore synthesis -> increased iron acquisition (limited in host)
Synthesis and secretion of proteins required for invasion/host submission
how adhesion affects host cell
Induction of cytokine release
upregulation of intercellular adhesion molecules (intergrins etc)
Induction of fluid loss
Apoptosis/ necrosis- to prevent further infection
Altered morphology
can be much more significant than effect caused by pathogen
how bacteria survive in host
host defences
defensins
fibrinogen
complement
antibodies
innate immune cells (neutrophils, macrophages)
strategies to survive the host defence
resistance to host defence
avoiding phagocytes
variation of surface antigens
protection against recognition by antibodies
capsule
M protein
Production of Fc- binding proteins to prevent interaction with Fc receptors on phagocytes- no antibody can bind
complement resistance
O- antigen polysaccharide chain ( part of LPS)- long chains hinder binding
Capsule- incorporation of sialic acid inhibits complement activity
active subversion of host defence
toxins
A-B toxins
Binding and entering host cell
pore formation
receptor mediated endocytosis
Enzymatic activity responsible for toxicity
membrane disrupting toxins- haemolysin
Anthrax toxin
anthrax produces spores which are highly resistant- if inhaled = disease and death very rapdily
All cattle carcasses due to unexplained sudden death have to be tested for anthrax before moved
Oedema toxin
causes oedema and necrosis
then septicaemia and shock in cattle and sheep
Haemorrhagic enteritis in pig and horses
Lethal toxin
stimulates cytokine release
oedema and necrosis
Superantigens
then excessive & and uncoordinated release of pro-inflammatory cytokines
Then TOXIC SHOCK SYNDROME
rashes
fever
multi-organ failure
DEATH
Stimulation of antigen presenting cells & T- cells
Bacterial effector proteins injected into host cells
Type III secretion systems
can kill cell
proteins injected into host cell and interfere with what cell does
can change non-phagocytic cells o be phagocytic
Intracellular vs extracellular survival
Intracellular
No exposure to immune cells, antibodies, defensins, complement
limited nutrients
can manipulate host via type III secretion systems- eg salmonella can make non-phagocytic cells phagocytic
can manipulate host via other systems- listeria, mycoplasma
Extracellular
there is exposure to immune cells, antibodies, defensins and complement
nutrient rich (glc, glutamine): iron limited
manipulation of host via type III secretion systems (pathogenic E. Coli)
Manipulation of hosts via other systems
Streptococcus equi
cause of strangles
rapid killing of neutrophils
toxins production-Streptolysin S causing cell lysis
antiphagocytic enzymes
prevention of phagocytosis
antiphagocytic enzymes
M- protein binding of fibrinogen to mask binding sites
hyaluronase capsule
travels through lymph nodes into horses head and neck
Colonisation of guttural pouches leading to long term survival in horses after they have recovered from strangles=> carriers that shed S equi without showing any clinical signs
summary
bacteria have a range of virulence factors to survive and/or manipulate the host response to infection, including toxins and type III secretion systems
sings of infection can be directly caused by bacterial virulence mechanisms or by the host response
bacteria can survve extracellularly
bacteria can mainuplate the the cytoskeleton to allow attachment invasion and intracellular suvival
while extracellularly nutrients are rich in supple except for iron, intracellular bacteria developed a range of mechanisms to access nutrients
intracellular survival
phagocytic cells
will actively take bacteria
designed to kill bacteria
forced phagocytosis
manipulate cells to phagocytose bacteria
manipulation of the host cytoskeleton
actin
microtubules
obtaining nutrients inside the cell
manipulation of host metabolism
poor access to nutrient inside cells and even worse inside the vacuole
how to not get killed straight away
modify vesicle trafficking
escaping the phagosome
moving inside the cytoplasm
bacteria exploit the host cell cytoskeleton for intracellular movment
cytoplasm is extremely viscous
inhibits diffusion
some bacteria use nucleation and assembly of host actin filaments at one pole of bacterium
growing filaments generate force
bacteria move
depolymerisation factors in cytosol depolymerise actin again - appearance of actin tail
moving between cells
actin tails
during cell division
clumps of bacteria at the spindle poles will be segregated into the two daughter cells when each infected cell divides
spreading from cell to cell without exposure to extracellular environment
not starving as an intracellular bacterium
cytosolic bacteria
direct use of host cellular glucose
inflammation increases glucose uptake by host cells
promote host autophagy
degradation of complex host macromolecules to release amino acids
intravacular bacteria
express glucose transporters into vacuolar membrane
manipulate vesicle transport
fusion with endocytic vesicles
cellular components convert polymeric nutrients into small building blocks and deliver them to pathogens
BOTH CAUSE MOBIDITY/MORTALITY
Both A- B toxins
DEATH