Mechanisms of bacterial Infection I Flashcards
What is symbiosis?
2 organisms existing together
What are 3 types of symbiosis?
commensalism
mutualism
parasitism
What is commensalism?
smaller organism takes benefit from host without causing harm
e.g. commensal flora in body
What is mutualism?
host and small organism benefit
opportunisitic
usually asymptomatic
What is parasitism?
small species harms host
full pathogen
lead to infection
The effect the pathogen has on a host depends on what?
balance between pathogenic mechanisms of the bacteria, and defensive mechanisms of the host
What are some pathogenic mechanisms of the pathogen?
adhesins:
toxins:
POLYSACCHARIDE capsules:
enzymes:
What do adhesins do?
allow the bacteria to adhere to mucosal surfaces which is one of the first steps in any pathogenic process
What do toxins do?
can damage the host,
undermine immune response
evades immune response
What are capsules?
defense structures on the outside that prevent the
pathogens from being attacked by antibodies and complements
What are host defence mechanisms?
natural barriers: skin and mucosal surfaces = elicit mucous and bile in the gut
tight junctions between epithelial cells- cilia on them= allows mucus clearance in lungs
lysozymes = tears and secretions
lactoferrin and acute phase proteins in the blood that chelate iron from bacteria that require it to grow
there are defensive cells, complement proteins and immune responses
According to Koch’s posulates, what criteria must be met to correlate a pathogen to a disease?
- microbe present in EVERY case of infection
- microbe has to be cultured from cases in vitro
- microbe must reproduce the disease in animals
- microbe must be able to be isolated from the infected animal
Can there be exceptions to koch’s postulates?
yes
-cant culture many organisms e.g. leprosy and syphilis
for infections like these, molecular tests e.g. PCR are done to show their presence
for some bacterial disease, you cant find the bacteria causing it-because it’s the product of the organism that is released into the host that
causes the disease
e.g. toxins produced by the organism B, cereus
What does the organism B cereus cause?
B cereus= food poisoning bacteria
-contaminates food, and if a person eats part of the food which is contaminated, it will lead to a toxin mediated disease
What is a local infection?
spots on skin
cholera
gonnorhea
What does V.cholera do?
lives on the gut adheres to epithelial cells of gut doesn't penetrate body but releases toxins effect on enterocytes leads to watery perfuse diarrhoea
Where does gonnorhea live?
mucosal surface of uroepithelial layers
cause mucosal inflammation
cause localized infections
What is an invasive infection?
enter lymphatics (not just on musocal surfave) e.g. shigella, staph aureus
What is a systemic infection?
spread via blood and lymph
infect other body parts
e.g. s, typhi N. meningitidis
How does tetanus act?
releases toxins and enzymes
secreted in one place but have effect on another place
What does shigella do?
cause watery diarrhoea
invades tissue causing submucosal tissue damage
What doe S.typhi cause?
typhoid
What is N.meningitis?
N mengitidis- gram negative bacteria causing meningitis
starts off as commensal organism
What are the stages of of bacteria causing an infection?
ACP MIDTR acquisition colonization penetration multiply and spread immune evasion damage host transmission and shedding resolution
What happens in acquisition?
get/acquire organism
breathe in, get in on skin- inject in through broken skin wound
What happens in colonization?
bacteria needs to ADHERE
IF It cant it gets cleared away in blood
What happens in penetration?
once adhered
bacteria release toxins and enzymes
allows them to penetrate into tissue
create an environment where they can survive
What happens with mulptiplication and spreading?
bacteria has made niche for itself, it now multiplies
spread locally or through blood
e.g. meningitis normally lives in nasopharynx, but can invade local mucosa and enter blood stream = cause meningitis (because it can evade all the immune attacks)
What happens in immune evasion?
if a bacteria cant evade the immune system, then it will get wiped out, but very serious bacterial infections have mechanisms to evade immunity
How can a bacteria cause damage?
triggers an inflammatory response
release of inflammatory mediators, toxins, and enzymes)
What happens in transmission and shedding?
bacteria damages host to allow bacteria to transmit to next host
e.g. V. cholera produces toxins that result in diarrhea, and as the bacteria are growing and multiplying in the gut, they are released into the environment through the diarrhea−it is worth noting however that the disease is not always required for transmission, there can be asymptomatic shedding
What is resolution?
driven by an antigen specific adaptive immunity - can clear infections
sometimes damage can lead to death even after resolution
Virulence factors are produced by bacteria to help with 3 main functions. What are they?
- promote colonization and adhesion
- to evade host defenses (to block complements, block neutrophils, hide their antigens etc)
- to promote tissue damage = necessary for the bacteria to grow and transmit itself eg toxins (exotoxins are secreted by the bacteria and have a mode of action away from the site of secretion)
What are the virulence factors?
adherence factors invasion factors capsules endotoxins exotoxins siderophores
What are adherence factors?
need for bac to adhere to mucosal surface
−contain pili, fimbraie (proteins with long fibrous nature- allow them to attach to epithelial cells)
What is a capsule?
outer surface polysaccharide capsules
prevent them from being opsonized by antibodies or binding complement proteins (the polysaccharide nature stops this from happening)
What are exotoxins?
proteins and enzyme released from a bacteria that have a different site of effect (can be cytotoxic, neurotoxic, enterotoxic etc)
What are siderophores?
whole series of proteins and binding proteins that bacteria release to compete for micronutrients from hosts
transferrin, lactoferrin and acute phase proteins produced by the liver (these reduce the amount of iron available for the pathogen to grow)
released by the bacteria to bind iron and they have iron binding capacities massively more than lactoferrin and our own iron binding proteins
What are endotoxins?
lipolysaccharides on gram negative
cause fever, change in bp, inflammation, lethal shock
What mechanisms drive tissue damage?
direct
innate
adaptive
What is the direct method of tissue damage?
microorganisms invade cells and cause cell lysis
microorganisms also release exotoxins that cause tissue damage
What is the innate method of tissue damage?
microorganisms release endotoxins = activate all components of the immune response that lead to macrophage activation, mast cell degranulation, neutrophil acquisition, clotting activation−these all lead to tissue damage
What are the adaptive immune mechanisms?
the generations of granulomas in diseases like Tb which cause necrosis (chronic inflammatory response to bacteria that cannot be killed by innate or adaptive immunity
T and B cells can be activated = cause direct damage to tissue (TCELLS)
OR create antibodies (BCELLS)
What does Bordetella pertussis cause?
whooping cough- can be mortal in children
now vaccines
not invasive- stays on mucosal surface of upper respiratory tract
How does Bordetella pertussis act?
- toxins cause damage
- cough and localized inflammation (last 3 months)
- toxins released to stop immune system clearing it
- toxins- cause inflammation- whoop sound when breathing
What is Vibrio cholerae?
non invasive bacteria in the gut lumen
attaches to enterocytes
releases toxins which affect the enterocytes
leads to watery diarrhea
What happens in Neisseria meningitidis?
- organism= lives in the nasopharyngeal cavities (normal commensal organism in quite a few people)
GRAM NEGATIVE
CUASED MAINLY BY ENDOTOXINS - occasionally invades
- causes bacteremia (bacteria in blood), septicemia, endocarditis (inflammation of the endocardium inner layer of heart), meningitis, endotoxemia (endotoxins in the blood)
What happens in Staphylococcus aureus?
- locally invasive bacteria
- produces a lot of toxins
- cause skin and wound infections
- very difficult to clear
- overcomes immunity
What happens in myobacterium tuberculosis?
- invasive pathogen
- starts in lungs
- gets phagocytosed by macrophages
- migrate to lymph nodes
- spread around body
- cause infection in bones, brain, lungs= miliary Tb (infection caused in every major organ)
What is the key pathological process in Tb?
Drive chronic granulomatous inflammation
What happens in Streptococcus pneumoniae?
- organism causes lobar pneuomina, bone infections, septicemia, meningitis
- part of childrne’s vaccine
What does Streptococcus pneumoniae have?
- outer capsule
- endotoxin like molecules = drive and dysregulate immune responses
- toxins that cause damage and local inflammatory responses
- mechanisms to evade immunity
What is streptococcus pyogenes?
group A strep
tonsilitis
sore throat
wound infections
How does streptococcus pyogenes adhere to host?
one of its adhesion molecules is structural component of cell wall called M protein fibrils
What are M protein fibrils?
adhesion molecules for streptococcus pyogenes
long polymeric proteins, and at the tip they have a very specific protein called an adhesin subunit that allows it to interact with very specific receptors on cells
What type of bacteria is Neisseria gonorrhoea?
gram negative diplococci
has huge long fibriae all over bacteria
can adhere to uroepithelial surfaces
What is the body defence against neisseria gonnorhoea?
flow of urine- takes and removes bacteria with it
How does neisseria gonorrhoea fight against urine?
bacteria has these long fimbriae
allows it to bind to epithelial cells- which are distance away
once it adheres, it contracts and brigns bacteria close to uroepithelial cells
How are exotoxins described?
proteins released from bacteria
enterotoxins = affect enterocytes in gut lumen produced by E. coli and V. cholera
neurotoxins= affect neural cells= e.g. TETANUS, BOTULISM
leukocidins= against white cells= released by STAPH AUREUS
ciliostatic toxins= stops ciliated epithelial cells working= RELEASED BY BORDETELLA PERTUSSIS- CAUSE whooping cough
What are the functions of toxins?
- promote adhesion
- promote survival or spread of bacteria like hyaluronidase and collagenase
- damage or destroy cells and cell membranes by using phospholipases and pores
- interfere with cell metabolism like cholera and diphtheria
- affect nerves
How many different types of toxins are there?
3
How do type 1 toxins act?
act at cell membranes
not transported into cell
cleave and damage surface proteins
damage metabolism or the ability of the cells to respond to signals
How do type 2 toxins act?
act on the cell membrane and damage it
exotoxins can create pores in the cell membrane damaging it
How do type 3 toxins act?
intracellular
after translocation
disrupt cellular function
What are the extraceullar functions of toxins?
damage the cellular matrix and connective tissue and destroys the tissue structure
once tissue structure is destroyed, the immune response cannot work= so cant recruit correct immune responses
What are examples of type 1 toxins?
E.coli produces toxin
super-antigen
toxins produced by staph aureus
toxins produced by strep pyogenes
Talk about toxins produced by E.coli
- genes code for enterotoxin= short polypeptide (temperature stable Ecoli)
- react with G protein on surface of enterocytes
- massive increase in cGMP inside enterocyte
- activate chloride channels and passive diffusion of water out of cell
- watery diarrhoea
What is a superantigen?
bacterial toxin
leads to T cell activation
but there isnt an acc antigen
(non antigen dependent clonal T cell activation)
What is strep pyogenes associated with?
scarlet fever
sore throat
What can some strains of strep pyogenes cause?
produce a series of toxins, and one of them is a super-antigen that leads to cytokine storms
-the cytokine storm causes desquamation of cells on the tongue forming a strawberry like appearance called strawberry tongue
−some of the other toxins in these genes cause an erythematous rash which is typical of someone who has scarlet fever
What do type 2 toxins do?
damage membrane by forming pores
What are type 2 toxins?
alpha toxin of staph aureus
streptococcus pyogenes
streptococcus pneumoniae
bacillus cereus causes food poisoning in uncooked rice produces cerolysin which forms pores
What does the alpha toxin of staph aureus do?
binds to cell membrane oligomerizes forms a heptamer pore this damages the membrane, and disrupts ion transport across the membrane cause tissue damage and cell death
What does streptococcus pyogenes produce to form a pore?
streptolysin
What does streptococcus pneumoniae produce to form a pore?
pneumolysin
What does bacillus cereus produce to form a pore?
cerolysin
Which enzymes directly damage cell structure?
phospholipases and hemolysin molecules
What is Clostriduim perfringens?
dangerous causes gangrene gram +ve rod bacteria - anaerobe - forms spores - found in soil and human gut
What virulence factors does clostridium perfringens have?
alpha lecithinases
phospholipase C = damages lipid membrane
it kills WBCs, RBCs and if it escapes into blood stream it causes severe hemolysis and death
What is the treatment for gangrene?
amputate
stop clostridium perfringens from spreading
What is Necrotizing fasciitis caused by?
strep pyogenes- group A strep
What is nectorizing fascitis?
beta hemolytic
strains carry a genes= form enzyme called cysteine proteases
once bacteria enter skin, they produce many enzymes and toxins
when the structural layers of the skin have been compromised, any inflammatory response will not get to where the bacteria is (as the structure of the tissue is disrupted)−the blood supply gets cut off•the bacteria spreads and spreads and eats away the whole structure of the tissue
What are the virulence factors of strep pyogenes group A?
- M proteins = adhesins
- streptococcal pyogenes exotoxins- A,B,C= toxins
- capsule (hyaluronic acid) = block opsonisation
(bc our cells have hyaluronic acid so bacteria is not recognized as foreign) - streptolysin and leucocidins =make pores in cell memb and damage WBC
What causes a pore in clostidirum perfringens?
perfringolysin
What do type 3 toxins do?
go into cells
cause damage
What is ADP ribosylation?
natural process
normally:after translation, enzymes modified to change its properties
ADP ribosylating enzymes= toxins
target proteins to stop cell metabolism and cause cell lysis
Which conditions can cause ADP ribosylating enzymes?
cholera
pertusiis (whooping cough)
diphtheria
What are Zn2+ dependent endopeptidases and where are they found?
neurotoxins
found in botulism and tetanus
What do the toxins target?
G proteins
protein synthesis by changing rRNA
actin and microfibril
What mechanism is inhibted in shigella?
protein synthesis
What bacteria causes shigella?
bacteria- shigella dysenteriae
What happens in shigella?
acute watery diarrhoea with blood and pus
means it invaded into local and submucosa
Which toxin does shigella involve?
toxin which has N-glycosidase activity
cleaves that 28s ribosomal RNA and stops the cell from making proteins
this affects enterocytes
What mechanism is inhibited in diptheria?
protein synthesis
What bacteria is involved in diptheria?
C. diptheria
What does C diptheria do?
- ADP ribosylates things
- targets elongation factor 2
- undermines protein synthesis causing cell death
- toxin release
What does C diptheria cause?
- upper respiratory tract infection
- production of a pseudomembrane consisting of pus and bacteria and fibrous tissue
- life threatening situation (through asphyxiation)
What does cholera produce?
watery poo
white colour
What does cholera toxin do?
cholera toxin binds receptor on cell surface
release active subunits that ADP ribosylate G proteins and activates adenylate cyclase
changes the activity of Cl-channels
activated of Cl-channels leads to hypersecretion of water leading to profuse watery diarrhoea
What causes tetanus?
clostridium tetani
What bacteria is clostridium tetani?
gram positive rod lives in soil forms spores anaerobic
What is tetanus?
metallopeptidase
targets protein in presynaptic vesicles of CNS
What does the tetanus block and what does this cause?
synaptobrevin = component of the vesicles
prevents release of neurotransmitters from interneuron
cause overexcitation of motor neurone from sensory neurone
leads to spastic paralysis
What causes Infantile botulism/floppy baby syndrome?
clostridium botulinum
gram positive anaerobe= forms spores
What happens in infantile botulism?
this toxic targets the presynaptic vesicles in the neuromuscular junction
this blocks the release of Ach which is the neurotransmitter at the NMJ
without Ach, there is flaccid paralysis
What is the difference between heat labile and heat stabile e. coli toxin causing diarrhoea?
Heat stable Activate guanylate cyclase High cGMP Activate protein kinase Ion channel disruption Chloride secretion Water follows Watery diarrhoeha
Heat labile Multimeric protein Stim adenylate cyclase More cAMP More protein kinase More chloride secretion More watery diarrehoa
