Mechanisms of Pathogenicity Flashcards
Pathogen
a pathogen is a microorganism that can cause a disease process
primary pathogen
always causes disease even in health immunocompetent individuals
Opportunistic pathogen
a microorganism that may cause disease if given the right circumstances
what are 3 examples of opportunistic pathogens and the circumstances in which they can infect?
- Candida albicans - immunosuppressed people (genetic problems or chemo therapy)
- Mucor species - diabetics [eye infection]
- Pseudomonas aeruginosa –> burn patients, Cystic fibrosis, HIV and neutropenic cancer patients
pathogenicity
ability to cause disease by evading or overcoming the host defences
virulence
the extent to which the microorganism is pathogenic
its the measure of pathogenicity
i.e. C.albicans has low virulence
Virulence Factors
molecules/structures produced by pathogens that contribute to their “pathogenicity” or ability to cause disease (help the organism cause disease)
what is an example of virulence factor
the capsule of Streptococcus pneumoniae (s.pneumoniae is only a pathogen when it has the capsule)
4 portals of entry for pathogens to gain entry to the host?
- mucous membranes
- skin
- parenteral route via mouth (i.e. ingesting)
- surgical sites and implants (bacteria/micro-organisms can latch on to them and get into the body that way)
Tropism
the cells and tissues of a host that support growth of a particular virus or bacterium.
Some bacteria and viruses have a broad tissue tropism and can infect many types of cells and tissues. Other viruses may infect primarily a single tissue.
6 determinants for tropism?
- Distribution of cell receptors for the microbes
- other competing microbes around
- accessibility of correct host cell types
- appropriate nutrients for growth
- physical and innate defences at the site of infection (the host’s age also plays into this)
- Permissive environmental condition i.e. pH
what are 4 examples of exotoxin producing bacteria?
- Corynebacterium diphtheriae (causes diphtheria) –> attaches to cells and produces exotoxins which moves through the blood and tissues
- Vibrio cholerae
- Clostridum tetani, botulinum, perfringens
- Bordetella pertussis
what is different about exotoxin producing pathogens?
they remain at the site of infection and do not spread through the system to cause disease; instead their toxins are produced and it gets into cells and causes the diseases process
What is the first step to infection?
adherence
how do pathogens adhere to host cells?
pathogens have structures called adhesins or ligands which recognize and bind to receptors on host cells
what are most adhesins made of?
glycoproteins or lipoproteins
what are most receptors on host cells made of?
sugars like mannose
adhesin possessed by N.gonorrhoeae bacteria
pili or fimbriae display adhesins (on tips of pili, helps bacterial attach to the surface of host)
adhesin possessed by S.mutans
glycocalyx for adhesion (produces capsule to attach to surface [causes biofilms to be made and plaque]
adhesins possessed by Enteropathogenic E.coli
specialized fimbriae that only bind to certain intestinal cells to cause diarrhea
10 factors that help the bacteria evade or penetrate host defences
- capsules
- cell wall components
- biofilms
- enzymes
- invasins
- sueprantigens
- toxins
- secretion systems
- antigenic variation
- intra/extracellular growth
How do capsules help bacterial evade host cell defences?
glycocalyx layer
initially prevents the phagocyte from recognizing and ingesting the bacteria (inactivates opsonin)
many bacteria can produce capsules in the right environmental conditions
What are three ways that cell wall components can help pathogens prevent opsonization?
- Fc Receptors on microorganisms prevent opsonization –> i.e. S.aureus has protein A on the cell wall which is a Fc receptor that binds to antibodies at the Fc end so phagocytes don’t find it and try to bind to it
- Streptococcus pyogenes –> has a protein “M” which is heat and acid-resistant protein in the cell wall that allows attachment of the bacteria to epithelial cells and inhibits phagocytosis
- Mycobacterium tuberculosis –> has mycolic acids which create waxy substances in cell walls make the bacterium resistant to digestion inside the phagocyte (makes it hard for the macrophage to break it down because its waxy)
How do biofilms help pathogens evade host cell defences?
- community for bacteria (same or different species), often surrounded by a shared glycocalyx layer (capsule) –> there is communication between bacteria in biofilm
(bacteria with capsules cause biofilm formations more) - biofilms educe antibiotic penetration and increases resistance [reduces antibiotic penetration because they are not actively metabolizing]
what are two examples of biofilms in the human body?
- Porphyromonas gingivalis in oral cavity
2. Pseudomonas aeruginosa in lungs, on medical implants
What are 7 exoenzymes (enzymes released from bacterial cells) that help bacteria evade host cell?
- Leucocidin –> destroys WBC
- Kinase –> breaks down fibrin and dissolves clots formed by the body to isolate the infection (important for the spread of the infection)
- Hemolysin –> breaks down red blood cells
- coagulase –> clots; converts fibrinogen to fibrin (protein strands) to form clots; the clot can wall the bacteria off from host defences
- Collagenase: breast down collagen
- lecithinase: destroys plasma membranes
- proteases: inactivate antibodies and other body proteins like IgA protease [breaks down IgA and allows the bacteria to attach to mucosal membrane]
what is an example of a bacteria that has Leucocidin exoenzyme?
S. aureus
Actinobacillus species
what is an example of a bacteria that has kinase exoenzyme?
Streptococcus pyogenes
what is an example of a bacteria that has Hemolysin exoenzyme?
staph, strep, listeria, clostridium
what is an example of a bacteria that has Coagulase exoenzyme?
Staphylococcus aureus
what is an example of a bacteria that has Collagenase exoenzyme?
Clostridium perfringens
what is an example of a bacteria that has Lecithinase exoenzyme?
Clostridium perfringens
what is an example of a bacteria that has proteases exoenzyme?
Neisseria gonorrhoeae
How do we do a coagulase test?
You take a test tube of rabbit plasma plus bacteria [fibrinogen is present in the plasma] and then you incubate it for 4-24 hours, then you check if a clot has formed or not by the presence of fibrin (insoluble). If coagulase is present, then you will get a positive result of clotting and if its not present, you get a negative result of no clot with no fibrin
How do invasins help pathogens evade host cells?
- invasins are surface proteins on some bacteria which activate actin, the cytoskeleton of eukaryotic cells
- rearranges and facilitates bacterial engulfment into the host cells
- they use the host cell cytoskeleton to get into the host cell
what are two examples of bacteria that use invasins to penetrate host cell wall?
Salmonella and E.coli –> use pedestal formation
Listeria monocytogenes uses re-arrangement of actin as a propellent
Shigella and Listeria –> use invasins to move from one host cell to another laterally by activating cytoskeleton. They infect intestinal epithelial cells laterally as well as from outside in, to avoid going detected by WBCs
What are super-antigens / Type 1 exotoxins?
aka Type 1 exotoxins
- they are protein antigens that stimulate a very large immune response
- less than 1% of t-helper cells are activated by an infection NORMALLY but with a superantigen as an activator, the response can be 20% T-helper cells activated (20X more cytokines)
How do super antigens (aka type 1 exotoxins) help pathogens evade host cells?
They unspecifically bind to MHC 2 and TCR around the binding groove
this results in excessive release of cytokines which results in nausea, fever, diarrhea, shock and death
what is an example of super-antigen bacteria?
Staphyloccocus aureus TSST-1 toxin which causes toxic shock syndrome
What are toxins?
toxins are virulence factors and are usually proteins that can produce fever, heart failure, diarrhea, deem and shock
they can destroy cells as well as inhibit protein synthesis, leading to cell death
What are two major types of Toxins?
- Endotoxin like lipopolysaccharide (Lipid A) [structural part of the bacteria]
- Exotoxin like super antigens (made by the ribosomes; and is an extra protein that the bacterial cell makes to affect cells other than itself)
what are endotoxins?
outer cell wall of gram negative bacteria (LPS)
LPS is made out of a polysaccharide and lipid A portion
the lipid A is the endotoxin and it is HEAT STABLE
causes chills, fever, weakness, aches, shock and death
activates the blood clotting system (DIC)
causes SHOCK (LOSS OF BLOOD PRESSURE) CALLED ENDOTOXIC SHOCK
What are exotoxins?
produced by certain types of bacteria and released into tissues (can be g+ or g-)
genes for these exotoxins can be carried by bacteriophages or plasmids
potent proteins and are heat sensitive (can get rid of it if u boil it)
our body has antitoxins to neutralize exotoxins
two common bacteria with exotoxins?
Colostridium botulinum (botox) flaccid paralysis due to botulism toxin
Clostridium tetani spastic paralysis (lock jaw) due to tetanus toxin
Common exotoxin structure
A-B toxin
A is toxic part
B binds to cells
How do secretion systems allow bacteria to get into host cells?
G- genes have a chromosome that codes for type 3 secretion apparatus; the chromosomal region where these genes are clustered is called Pathogenicity Island
it forms an apparatus that can shoot the baccterial secretions into the host cell like a needle
Type 3 secretion apparatus
enables G- bacteria to inject proteins into host cell, killing or altering it
the needle can puncture holes into host cells and the secretions it releases into host can kill it
How does antigenic variation allow bacteria to evade host cells?
it fools the immune system
pathogens have antigens on their surface where the host B-cells will form antibodies to
- some pathogens change the make up of their antigens as they replicate (called mutation)
immune system sees those mutated antigens on the same pathogen as NEW PATHOGEN and the previous antibodies do not work
what are two bacteria that use antigenic variation
neisseria gonorrhoeae and trypanosome species
Obligate intracellular bacteria
can only grow inside of host cells in a protected vacuole and cant make their own ATP
two examples of obligate intracellular bacteria
chlamydia and rickettsia
facultative intracellular bacteria
bacteria that can multiply outside of host cells, but often use intracellular growth as a means of evading the host defences
3 examples of facultative intracellular bacteria
- bordatella
- mycobacterium
- salmonella
Three methods of horizontal gene transmission
- conjugation: transfer of plasmids containing genes for virulence or antibiotic resistance
- Transduction: acquisition of genes for toxin production (c. diphtheria bacteria by transfer of bacteriophage)
- Transformation: acquiring a new gene for toxin, capsule production etc.. but absorbing naked DNA in the environment around the bacteria
plasmids
small circular DNA molecules that are seperated from the main bacterial chromosome
- encode for antimicrobial resistance or virulence factors
Bacteriophages
viruses which infect specific bacteria and transfer these genes to another bacteria via transduction
example of bacteriophage infecting a bacteria
Corynebacterium diphtheriae
not pathogenic unless its lysogenized by a phage and then produces the toxin
How are the pathogenic effects of viruses different from bacteria?
different from bacteria because of the nature of the virus, which invades the host cells and resides intracellular (in the cell) and is protected from the immune cells
what do most viral pathogenesis cause?
inflammation and activation of immune system which produces disease
Two forms of viral pathogenesis?
- Cytopathic effects (CPE)
2. Syncytium formation
cytopathic effects (CPE)
killing or damaging of the host cell by the virus
causes host cells to become round
different strains of virus cause different CPE
Syncytium formation
this occurs when virally infected cells fuse together to form a giant multi-nucleated cell
this cell eventually dies when the viruses use up all the building material and cause tissue necrosis
this permits viral multiplication without exposing the virus to antibodies (blocks it off)
which viruses cause syncytium formation?
RSV and measles
what are two ways viral cells can evade immunity?
- downregualte MHC1 (prevent it from being produced by the cell)
- Syncytium formation
what are three ways viruses can disrupt cellular life cycle and activity?
- inhibit macromolecular synthesis of host proteins/ mitosis
- cause host cell to release enzyme in lysosomes resulting in cell death
- deregulate cell function like affecting hormone production
what are two ways viruses can cause cancer?
- induce chromosomal changes in cells i.e. oncoviruses
- deregulate contact inhibition –> when one cell bumps into another cell, it usually bounces off, but if thats deregulated then it will attach to it and keep growing (uninhibited cell growth)
