Chapter 15- Microbial mechanisms of pathogenicity Flashcards
Pathology
scientific study of disease
Etiology
the study of the cause of the disease
Pathogenesis
the manner in which a disease develops
Infection
the multiplication of any parasitic organisms. Can lead to disease sometimes, but not always
Disease
A disturbance in the state of health where the body can’t carry out all of its normal functions. When you have signs and symptoms that deviate from normal structure and function
Pathogens
Any organism that can cause disease
Signs of disease
Objective and measurable, directly observed by a clinician when examining a patient. Includes changes in vital signs, fever. blood cell counts
Symptoms of disease
Subjective, felt or experienced by a patient but can’t be confirmed or measured. Includes pain
Syndrome
A collection of signs or symptoms that occur together and indicate a specific disease or infection (a specific group of signs and symptoms)
Infectious disease
Caused by infectious agents. Bacterial, viral, parasitic. Can be transferred from one host to another and is caused directly by a pathogen
Noninfectious disease
Caused by some other factor, like a poison. Non-communicable disease cannot be spread from host to host- food poisoning, tetanus
Iatrogenic disease
Contracted as the result of a medical procedure. Also acquired in a hospital setting, but occurs in specific circumstances. A procedure like surgery is one example
Nosocomial disease
acquired in hospital settings- by anyone, not just a patient
Zoonotic disease
transmitted from animals to humans. Coronavirus is an example
Subclinical disease
No noticeable signs or symptoms (inapparent infection), like someone who has been infected but is asymptomatic (can occur with COVID). Only considered asymptomatic if you’re not taking any medication
Incubation period
Time between acquiring an infection to the appearance of signs/symptoms. The disease can be transmitted at this point. Depends on many factors- the dose of the infectious pathogen, the host’s status (pre existing disease), the pathogenicity of the microorganism (does it produce a lot of virulence factors)
Prodromal phase
Short period where nonspecific mild symptoms occur- this is when you first start not feeling well. Headache, fatigue, etc
Prodrome
A symptom indicating the onset of disease
Invasive phase
When you start expressing typical signs and symptoms of the disease- fever, swollen lymph nodes, sore throat, headache, nausea. Most infections don’t go past this stage- the host immune response disables the pathogen before it causes symptoms
Fever
Generally seen during the invasive stage of disease. It is a protective mechanism to fight infection. High temperatures help the immune system and certain enzymes to function better and inhibits microbial growth. Organisms that infect humans are normally mesophiles and can’t survive at higher temperatures. Use of antipyretics can actually prolong the infection
Acme
The critical stage or crisis of a disease. When pathogens invade and damage the host tissues. This is the point where the disease can become chronic. This is like when a fever reaches a high point and breaks, and the person recovers
Decline phase
Declining signs and symptoms. The host defenses start to kick in and the treatment you started during the invasive phase starts working. People are still susceptible to secondary infections at this stage- like developing bacterial pneumonia after the flu- the lungs become damaged and create a good environment for bacteria
Convalescence period
When your tissues are repaired and healing takes place. People can still be infectious- they can be infectious in all stages of disease depending on the pathogen. Smallpox is an example- scabs still carry the virus during the convalescence period
Stages in the course of an infectious disease (6)
- Incubation period
- Prodromal phase
- Invasive phase
- Acme
- Decline phase
- Convalescence period
Sequelae
Occurs when you still have lasting effects from the disease, even after the convalescence period is completely over- this doesn’t happen to everyone. It is sometimes caused by the host’s response to the infection, anti inflammatories or immunosuppressants can be used to decrease the immune response and prevent this from happening. Can include scarring, kidney or heart damage
Acute disease
Symptoms develop rapidly, like strep throat
Chronic disease
Disease develops slowly, over weeks or months or even over a lifetime. Slow to resolve. Tuberculosis is an example
Subacute disease
Symptoms between acute and chronic. Symptoms develop more slowly than acute but can last longer, like chronic. Bacterial endocarditis is an example
Latent disease
Disease with a period of no symptoms when the causative agent is inactive. Herpes, varicella zoster, and HIV are examples
What is the purpose of Koch’s postulates?
They are a systematic approach to identify the causative pathogen of a disease
Koch’s postulates (4)
- The suspected pathogen must be found in every case of disease and not be found in healthy individuals
- The suspected pathogens can be isolated and grown in pure culture
- A healthy test subject infected with the suspected pathogen must develop the same signs and symptoms of disease found initially
- The pathogen must be re-isolated from the new host and must be identical to the pathogen used to inoculate the organism
Stanley Falkow
Created a revised form of Koch’s postulates (molecular postulates) in 1988. Their premise is not the ability to isolate a particular pathogen but rather to identify the gene that may cause the organism to be pathogenic
Molecular Koch’s postulates (3)
- The phenotype of the disease should be associated only with pathogenic strains of a species- E. coli has nonpathogenic strains
- Inactivation of the suspected genes associated with pathogenicity should result in a measurable loss of pathogenicity- inactivating a gene of pathogenic E. coli means that the Shiga toxin is not produced
- Reversion of the inactive gene should restore the gene phenotype- the Shiga toxin should be able to cause disease again
Pathogenicity
capacity to produce disease or harm the host. Depends on the number of infectious organisms that enter the body, virulence, and attenuation
Virulence
intensity of the disease produced by the pathogen. How many toxins or proteins that disrupt normal functions can it produce (the ability to produce virulence factors)
Attenuation
Weakening of the disease-producing ability of the pathogen. Some organisms are very virulent at first and become less virulent as they pass to other hosts. Pathogens will not be able to survive if they are so virulent that they kill all their hosts. Attenuation is used as a means of vaccination- an attenuated pathogen can cause an immune response, but is not as virulent
ID50
Infectious dose for 50% of the test population- the dose required for an animal to get sick
LD50
Lethal dose for 50% of the test population- the dose required to kill the animals
Primary pathogen
always causes disease whenever it’s present
Opportunistic pathogen
Can only cause disease when the host’s defenses are compromised- when the immune status or health status changes
Steps of pathogenesis (5)
- Exposure or entry
- Adhesion (tissue attachment and colonization)
- Invasion
- Infection/host damage
- Pathogen exit
Pathogens are characterized by the presence of virulence factors. They must achieve all of these stages to cause disease
Exposure and entry to the host
Not all contact causes infection or disease- a pathogen has to be able to infect the susceptible host tissue. Pathogens enter through portals of entry
Portals of entry
The points where the pathogens are able to enter the body. Placenta, eyes, nose, mouth, broken skin, anus, urethra, vagina
Adhesion molecules
Help the pathogen to stick to a cell
Toxins
Imbalances the host’s cells and can kill the cells. Dead cells can produce nutrients that the cells need. They contribute to food poisoning
Superantigens
Toxins that can cause a massive immune response due to the release of cytokines from host cells. Can cause shock, fever, and many other issues
Virulence factors (3)
- Adhesion molecules
- Toxins and superantigens
- Enzymes
They harm the host or prevent the pathogen from being detected by the host
Virulence factors (3)
- Adhesion molecules
- Toxins and superantigens
- Enzymes
Examples of virulence factors (5)
- Bacterial pili
- Enzymes that harm the host or prevent detection
- Proteins that disrupt normal cellular function
- Capsules
- Enzymes that inactivate antibiotics- they are encoded genetically
Adhesion
Ability of a pathogen to attach to the cells using adhesion factors (adhesins)
Adhesins
Protein molecules found on the surface of several pathogens and bind to glycoproteins (receptors) on host cells. Can be found on bacteria, viruses, fungi, parasites. Found in type 1 fimbriae, type 4 pili, the cilia of protozoa, part of capsids, part of cell walls, or viral envelope receptors
Examples of adhesins (3)
- Glycocalyx- streptococcus mutans
- Fimbriae- E. coli
- M protein- streptococcus pyogenes
Type 1 fimbriae
Static hair-like appendages used only for attachment- like a needle which can bind to specific glycoproteins
Type 4 pili
dynamic, thin, and flexible. They can repeatedly extend and retract which allows for twitching motility. Found in gram negative bacteria, allow them to adhere to new cells
Invasion
The dissemination of a pathogen throughout local tissues or the body- pathogens produce exoenzymes and toxins. Toxins allow microorganisms to colonize and damage the host tissues
Intracellular pathogens
Some pathogens don’t just infect tissues, but the cell itself. They are called intracellular pathogens, and by living in the cell they are able to evade some mechanisms of the immune system. Obligate intracellular pathogens need to reproduce in the cell while facultative intracellular pathogens can reproduce inside or outside of the cell
Exoenzymes
enzymatic virulence factors help bacteria invade tissue and evade host defenses
Glycohydrolase
degrades hyaluronic acid that cements cells together to promote spreading through tissues
Nucleases
degrade DNA released by dying cells (bacteria and host cells) that can trap the bacteria, promoting spread
Phospholipases
degrades the phospholipid bilayer of host cells, causing cellular lysis, and degrade the membrane of phagosomes to enable escape into the cytoplasm
Proteases
degrade collagen in connective tissue to promote spread of bacteria
S. aureus exoenzyme
S. aureus can also produce an exoenzyme called coagulase. It causes a blood clot to form around the pathogens to protect them. The immune system will not be able to recognize the pathogens. The pathogens then produce streptokinase, which dissolves the clot and releases the bacteria
Toxin
substance that contributes to pathogenicity
Toxigenicity
ability to produce a toxin
Toxemia
the presence of a toxin in the host’s blood
Toxoid
inactivated toxin used in a vaccine
Antitoxin
antibodies against a specific toxin
Exotoxins
Proteins produced inside pathogenic bacteria, typically gram positive bacteria, as part of their growth and metabolism. They are secreted into the surrounding medium during log phase- by products of the growing cell. They do not cause fever and can be neutralized by antitoxin. Their lethal dose is small. Unstable, denature above 60 degrees Celsius and due to UV light. Cholera toxin, Shiga toxin, botulinum toxin are examples
Endotoxins
Lipid portions of lipopolysaccharides (LPS) that are part of the outer membrane of the cell wall of gram negative bacteria- they are released when the bacteria dies and the cell wall breaks apart. Cause fever and activation of clotting factors (can lead to the production of clots). Activate the immune system, can cause vasodilation (decreases blood pressure and can cause shock). They are more dangerous because they can’t be neutralized by antitoxin and the lethal dose is large
Which type of antigen is used for strain identification?
The O antigen of endotoxins is used for strain identification and to differentiate between different types of bacteria
Which type of toxins allow for toxoid conversion?
With exotoxins, toxoid conversion is possible by heat or chemical treatment, toxoid can be used against the toxin (it is used as an antitoxin). Therefore, only exotoxins can have vaccines produced against them.
Exotoxins mechanisms (8)
- Plasma membrane disruption
- Cytoskeleton alterations
- Protein synthesis disruption
- Cell cycle disruption
- Signal transduction disruption
- Cell-cell adhesion disruption
- Vesicular trafficking
- Exocytosis
Exotoxin plasma membrane disruption
The toxins form pores on the plasma membrane. E. coli alpha toxin and S. aureus alpha toxin are examples
Exotoxin cytoskeleton alterations
Can cause the host cell actin to polymerize . Actin maintains cell shape and acts like highways for vesicle movement. Botulinum toxin is an example
Exotoxin protein synthesis disruption
Target eukaryotic ribosomes and prevent protein synthesis from occurring. Diptheria toxin and Shiga toxin are examples
Exotoxin cell cycle disrupton
Can stop or stimulate cell division. Cytolethal distending toxin (E. coli) stops cell division, while pasteurella toxin stimulates cell division
Exotoxin signal transduction disruption
Subvert the host cell’s secondary messenger pathways and increase or decrease the synthesis of signaling molecules like cyclic AMP. cAMP synthesis triggers the cell to think there is less ATP, so the cell will produce more energy. Can also trigger an excessive activation of the immune response. Cholera toxin, pertussis toxin are examples
Exotoxin cell-cell adhesion disruption
Toxins cleave the proteins that bind host cells together. They don’t need to be processed by cells, they will automatically activate the immune system. Staphylococcal exfoliative toxin is an example
Exotoxin vesicular trafficking
Cause vesicles to form in the cell and create a large vacuole, which damages the cell. H. pylori VacA and
Aerolysin are examples
Which exotoxins work by exocytosis? (2)
- C. botulinum neurotoxins
- Tetanus toxin
How do endotoxins and exotoxins differ in terms of specificity?
Endotoxins are less specific and mainly trigger an immune response. Exotoxins are very specific in the cellular structures they target and can impact specific organs and tissues
AB toxin mechanisms (4)
- The B subunit binds to the cell membrane, and is bound to the A subunit
- The binding of the B subunit to the membrane causes the eukaryotic cell to engulf the toxin.
- Once the toxin is inside a vacuole, the A subunit is released
- When the A subunit is released, it can disrupt protein synthesis by binding to the ribosomes or through other mechanisms
AB toxins
The A subunit is toxic (A for activity). The B subunit binds host cell receptors
(B for binding). Many B subunits are complexes of 5 units arranged as a ring. Diphtheria toxin is an example of an AB toxin, Shiga toxin is another example
Infection
Successful multiplication of the pathogen leads to infection
Primary infection
acute infection that causes the initial illness
Secondary infection
Opportunistic infection after a primary (predisposing) infection. Tends to occur after the acme stage of illness
Local infection
pathogens are limited to a small area of the body
Systemic infection
an infection throughout the body
Focal infection
systemic infection that began as a local infection
Sepsis
Toxic inflammatory condition arising from the spread of microbes, especially bacteria or their toxins, from a focus of infection. A lot of times, this can occur due to endotoxins
Bacteremia
bacteria in the blood
Septicemia
growth of bacteria in the blood
Toxemia
toxins in the blood
Viremia
viruses in the blood
Phagocytosis of a pathogen
The pathogen attaches to the host cell membrane and injects protein effectors into the cell. Then, the pathogen induces phagocytosis. Once inside the phagosome, there are 4 possibilities
4 possibilities once a pathogen is inside a phagosome
- The pathogen goes into the cell and is killed inside the phagosome
- Inclusion bodies
- Pathogens like Salmonella can remain inside of a phagosome and prevent fusion with the lysosome
- Pathogens like Shigella and Listeria break out of the phagosome and then move throughout the cytoplasm into adjacent cells by forming actin tails
Inclusion bodies
Pathogens such as Coxiella are obligate intracellular organisms. They allow the cellular lysosomes to bind to the phagosomes. The bacteria differentiates into a form that is able to replicate in the phagolysosome, which results in inclusion bodies.
What happens when pathogens prevent fusion with the lysosome?
Pathogens like Salmonella can remain inside of a phagosome and prevent fusion with the lysosome. Salmonella Typhi will remain in the phagosome, which moves to the host membrane and expels Salmonella into the extracellular space. From there, the bacterium can be engulfed by a macrophage and survive within the phagosome. The macrophage can travel to regional lymph nodes and disseminate the organism through the circulatory system
Pathogen actin motility
Pathogens like Shigella and Listeria break out of the phagosome and then move throughout the cytoplasm into adjacent cells by forming actin tails. They can then move through actin motility and move through the cytoplasm into adjacent cells. It enters a phagosome as it enters the new cell. As it moves, it releases virulence factors and damages tissues
FC antibody region
Causes the antibodies not to recognize the pathogen
Quorum sensing
Used to communicate with other pathogens about population size. Proteins or certain chemicals are used in quorum sensing
Extracellular immune response avoidance (3)
- Capsules coat bacterial cell walls and can prevent phagocytes from binding
- Cell surface proteins- cell wall components that prevent detection
- Quorum sensing
Antigenic variation of viruses
100 known serotypes of rhinovirus, each virus has a unique capsid protein. Antibodies to one capsid protein are not effective on another
Antigenic shift
two strains of influenza virus infect the same cell and the genomes get mixed. This makes a dramatically different virus
Antigenic drift
random mutations can occur within the cell that a virus infects, creating small changes in virus proteins
Latent herpes virus
Herpes virus goes into latency and incorporates its genome into the host cell. During periods of stress, the virus re-circulates and reactivates, causing lesions. Small RNA molecules called microRNAs (miRNA) are made by herpes virus that interfere with the host cell’s apoptosis program. This causes the cells to die/basically kill themselves. During this process, no viral proteins are made to avoid immune detection
Antigenic masking
Some protozoans coat themselves in host antigens to avoid detection by the immune system. Coat themselves with proteins from the human host so the immune system doesn’t recognize them as foreign
Antigenic variation of protozoans
just like viruses and bacteria, some protozoans can alter their surface antigens to prevent antibody binding
Intracellular location
just like some bacteria, protozoans have found ways to live inside the host cell to prevent detection
Immunosuppression (protozoans)
some protozoans induce the secretion of anti-inflammatory cytokines to reduce the innate immune response
Portals of exit
How pathogens exit the body. Eyes, nose, mouth, ears, urethra, broken skin, anus, vagina, sweat glands, breast milk
