Lec #4 (Wk 1): Bacterial Pathogenesis Flashcards
What is a pathogen?
A micro-organism that causes a disease. A pathogen could be:
- Virus
- Prokaryote (bacteria)
- Protozoa
- Prions (proteins that can trigger normal proteins in the brain to fold abnormally)
- Fungi
- Parasites
What is pathogenesis?
How diseases begin and develop.
What is pathogenicity?
The ability of a pathogenic agent to cause disease.
What establishes a causative relationship between a microbe & disease?
Koch’s postulates - 4 criteria designed to establish this.
Postulate 1 –> the microorganism must be found in abundance in all organisms suffering from the disease BUT absent in healthy organisms.
Postulate 2 –> Micro-organism must be isolated from a diseased organism and cultured.
Postulate 3 –> The cultured microorganism should cause disease when introduced into a healthy organism.
Postulate 4 –> the microorganism must be reisolated from the experimental host and identical to the original specific causative agent.
What are the factors affecting pathogenesis?
The host, pathogen, & environment can all influence how a pathogen starts and develops.
Host:
- Immune status
- Genetic susceptibility.
- Behavioral risk factors.
Pathogen:
- Virulence genes.
- Virulence related genes.
Environment:
- Temperature
- H2O availability
- pH
What are the steps of pathogenesis?
1- Route of entry.
2- Evasion & survival.
3- Adherence & attachment.
4- Colonization at the site of adherence.
5- Disease symptoms caused by bacterial toxins or invasion.
Evasion –> strategies that the bacterial pathogens use to avoid or inactive the host defenses and ensure their survival.
What are the different entry portal for pathogens & state examples of bacteria in each route of entry.
1- Respiratory
- Mycobacterium tuberculosis.
- Haemophilus influenza
- Streptococcus Pneumoniae
2- Skin
- Clostridium Tetani
3- GIT
- Salmonella
- Vibrio Cholera
- Shigella Dysenteriae
4- Genital
- Neisseria Gonorrhoeae
Will we still have a disease if a pathogen is supposed to enter through the skin but does so through the GIT?
No, entry portals are specific.
What does evasion mean & what are the different ways that pathogens cause evasion?
Evasion is the way in which pathogens avoid detection by the host.
1- Inhibit phagocytosis.
2- Secrete toxins to modulate the cell death pathways.
3- Modulate surface structure to avoid being recognized.
How does staphylococcus Aureus cause evasion & survival within a host?
They secrete a protein called Staphylococcus Aureus Protein A (SpA). This protein inhibits phagocytosis through 2 different ways:
1- SpA can bind to the Fc region of the antibody which means the Fc region of the antibody is now covered and can no longer bind to the Fc receptor present on the surface of the neutrophil, hence neutrophil cannot perform phagocytosis.
2- SpA protein can bind to the Fab region of the antibody & these antibodies are located on the surface of the B-cell. This consequently stimulates the death of the B-cell and can no longer secrete antibodies specific to the S-aureus so B-cells undergo apoptosis thus reducing phagocytosis.
How does Neisseria Meningitidis cause evasion & survival within a host?
Neisseria Meningitidis produces Neisseria Meningitidis Factor H Binding Protein (fHBP) and this binds to factor H (factor H usually stimulates C3b), so by binding to Factor H, C3b is inactivated.
So when fHBP binds to factor H –> minimize complement activation and enhances survival of this bacteria.
What are the different bacterial adherence factors?
- Fimbriae
- Pilli
- Capsule
- Lipotechoic acid & techoic acid
- Lipopolysaccharide (LPS)
- Adhesin
What does colonization mean? How does it occur?
Colonization is the establishment & growth of a microorganism on a body surface.
1- Enter lumen of the new host & pass through the mucus.
2- Bind to the epithelium via host surface carbohydrates and proteins.
3- Obtain nutrients from the host.
4- Avoid host cellular & humoral immunity.
5- Exploit inflammation to exit or invade host.
What does virulence mean? How does it differ from pathogenicity?
Virulence is the degree of pathogenicity. So pathogenicity is more of a qualitative variable (i.e yes or no, is it capable of causing a disease?) whereas Virulence is quantitative, it tells us the level/extent of damage that an organism can cause to the host.
How can we measure bacterial virulence?
Measured by looking at the no. of bacteria required to cause the disease.
Infective Dose (ID) 50 –> the amount of bacteria required to infect 50% of the animals exposed.
Lethal Dose (LD) 50 –> the amount of bacteria required to kill 50% of the animal exposed.
What is the ID50?
Infective Dose 50 is the amount of bacteria required to infect 50% of the animals exposed.
What is the LD50?
Lethal Dose 50 is the amount of bacteria required to kill 50% of the animals exposed.
What are virulence factors? Examples?
Virulence factors are molecules produced by the bacteria that enables them to achieve all the steps of pathogenesis.
Examples:
- Flagella
- Adhesion Pilli
- Capsule
- Virulent enzyme
- Iron binding proteins
- Toxins (Endo & exotoxins)
- virulent surface proteins.
- LPS
Flagella’s role in acting as a virulent factor?
A factor to swim to reach the specific tissue or organ.
Outer capsule’s role in acting as a virulent factor?
Outer capsule helps in adhesion & resists phagocytosis. It is non-antigenic because it is identical to that found on the CT.
E.g: streptococcus pyogenes have hyaluronic acid capsule.
LPS’s role in acting as a virulent factor? E.g?
It is a glycolipid found at the outer membrane which is a factor to adhere to the surface & interact w the host.
Helicobacter Pylori, the LPS plays a key factor to establish colonization & persistence in the gastric niche.
Iron binding proteins role in acting as a virulent factor?
The ability to acquire iron in an iron-poor environment during infection is necessary for some bacteria. Thus, bacteria secrete proteins with high affinity for iron.
Those proteins:
- Heme-binding proteins (Hemophores).
- Siderophores.
- Transferrin or Lactoferrin-bound iron.
- Soluble Fe2+
Virulent enzymes role in acting as a virulent factor? Their classes?
Some pathogen produce extracellular enzymes (exoenzymes) to enable them to invade host cells & deeper tissues.
Classes:
- Glycohydrolases
- Proteases
- Phospholipases
- Nucleases
One of the virulent factors are virulent enzymes. One of the classes of these virulent enzymes is glycohydrolases, talk about it.
An example of glycohydrolases is hyaluronidase which is an enzyme inducing host tissue damage. This enzyme is produced by pathogen like staphylococcus aureus, streptococcus pyogenes, & clostridium perfringens.
So these bacteria secrete hylauronidase which degrades the hylauronic acid which acts as an intracellular cement between adjacent cells in the CT.
One of the virulent factors are virulent enzymes. One of the classes of these virulent enzymes is proteases, talk about it.
Collagenase is an example of a protease that is produced by some bacteria like clostridium perfringens. It helps degrade the collagen present between the cells in the connective tissue.
One of the virulent factors are virulent enzymes. One of the classes of these virulent enzymes is nucleases, talk about it.
An example of nuclease is DNAse which some bacterias like staphylococcus aureus & streptococcus produce. So when a bacterial+host cells die at the site of infection, they release their intracellular content include the DNA chromosome which is the larger out of all. So this large mass of DNA can trap bacteria & prevent their spread. So DNAse help to degrade this mesh to enable the bacteria to penetrate further.
One of the virulent factors are virulent enzymes. One of the classes of these virulent enzymes is Phospholipases, talk about it.
Enzymes which degrade the phospholipid of the cell membrane & cause lysis of target cells.
Examples: Clostridium perfringens produce phospholipase, and B. anthracis bacteria produces phospholipase C.
The role of phospholipase in bacterial virulence is phagosomal escape. When B. anthracis is ingested by phagocytic cells, it can degrade the membrane of the phagosome before fusing w the lysosome, allowing the pathogen to escape.
Which pathogen is responsible for producing phospholipase C?
B. anthracis which is responsible for the disease anthrax.
What are coagulases & kinases?
Coagulase –> enzyme which clots the fibrinogen in the blood (i.e the bacteria outside of the blood vessel, fibrinogen exits the blood vessel to the site of bacteria and is converted to fibrin to create a clot around this bacteria) in order to protect the bacterium from phagocytosis & isolate them from other immune cells.
Kinases –> enzyme released by bacteria which breaks this clot that coagulase helped to create, thus breaking free the bacteria and helping it to spread and cause bacteremia (bacteria in blood stream).
Which bacterial enzyme contributes to bacteremia?
Kinase.
Breaks the clot created around the bacteria by the coagulase and allows the bacteria to spread and enter the blood vessels.
What are bacterial toxins?
They can be small molecules, peptides, or proteins produced by the bacteria. they are capable of invading & causing damage to the tissues. They are often responsible for major symptoms of bacterial infection.
What does toxigenicity mean?
The ability of a pathogen to produce toxins to cause damage to the host cells.
What was first to be discovered as a virulence bacterial toxin?
Diphtheria toxin.
What are the types of toxins available?
Exotoxins
Endotoxins
What are exotoxins?
They are proteins made up of 2 parts: part A is the effector, part B binds to the receptor and are joint by a disulfide bond, produced by the bacteria, usually released by Gram-positive bacteria, and released after lysis happened.
Action: SPECIFIC. So each exotoxin targets a specific receptor on specific cells.
Heat stability: most exotoxins aren’t heat stable and denatured at temperatures above 41 degrees.
Lethality: very small concentrations of exotoxins can be lethal.
Provide examples of diseases caused by exotoxin release?
Diphtheria
Tetanus
Botulism
Where are the genes of exotoxins commonly found?
Plasmids or phages.
What are endotoxins?
They are the lipid portion of the LPS that are part of the cell wall of gram-negative bacteria. Released when the bacteria dies and the cell wall breaks apart.
