Driessen lecture 4: Microbial infection and pathogenesis, antibiotics Flashcards
What is the difference between disease and infection?
Infection implies the growth of a microorganism in or on a host, whereas disease refers to actual tissue damage that impairs host function.
How does a pathogen ‘know’ that is has arrived at a suitable infection site?
Receptors on pathogens have evolved to bind specifically to complementary molecules in the host, and the
complementary nature of the receptors on pathogen and host cells alerts the pathogen that it has arrived on a suitable infection site.
What event is required but not sufficient to cause disease?
Adherence is the first
step, and although adherence is required to initiate disease, it is not
sufficient to initiate disease because the host has many innate defenses that can thwart infection.
How can capsules enhance/ facilitate adherence to host tissues and what are their functions besides this?
Capsules can facilitate adherance to host tissues through:
* Specific receptors that facilitate adherence to host tissues
* The inherently sticky nature of capsules facilitates adherence.
Besides adherance, capsules are important for protecting bacterial pathogens against host defenses (example: Streptococcus pneumoniae)
How and where does N. gonorrhoeae cause disease?
N. gonorrhoeae adheres specifically to mucosal epithelial cells in the genitourinary tract, eye, rectum, and throat and it does this with its surface protein Opa (opacity associated protein). Opa binds specifically to host proteins only found in these body regions. Along with Opa, pili of N. gonorrhoeae play a key role in attatchement to urogenital epithelia.
By way of which protein does influenza virus attatch itself to upper respiratory tract mucosal cells?
By the protein hemagglutinin present on the virus surface.
What are the two Streptococcus species most often associated with tooth decay?
S. sobrinus and S. mutans
Which material from saliva forms a thin film on teeth that is the perfect attatchment site for bacterial cells?
Acidic glycoproteins from the saliva.
What is the trigger for decay activities by the bacteria?
Sucrose (table sugar) since it is sucrose that allows these species to produce the dextran exopolysaccharide and capsules necessary for attachment and colonization.
How does the capsule of Streptococcus mutans assist in the formation of dental caries?
The capsule of S. mutans contains adhesins specific for host salivary glycoproteins.
Describe the terms bacterimia, septicemia, and viremia. Name an example of viremia.
- Bacterimia is the mere presence of bacteria in the bloodstream, and it not harmful, because the bacteria don’t grow in the bloodstream.
- Septicemia, on the other hand, is when bacteria multiply in the bloodstream and produces toxins or other poisonous substances. (Massive inflammation and other symptoms)
- Viremia is when there’s viruses present in the bloodstream (measles).
What are virulence factors?
Virulence factors are toxic or destructive substances produced by the pathogen
that directly or indirectly enhance invasiveness and host damage by facilitating and promoting infection.
What is attenuation of a viral pathogen?
Attenuation is the decrease or loss of virulence of a pathogen.
What is an opportunistic pathogen?
What is a nosocomial infection?
- An opportunistic pathogen is a pathogen that can only cause disease when the hosts immune system is compromised. In a normally functioning immune system, it can’t and won’t cause disease, but when the immune system is compromised (due to genetic or environmental factors, or other noninfectuous diseases like cancer) it will cause disease.
- A nosocomical infection is a healthcare-associated infection (because the hosts are compromised, or because pathogens are introduced during things like surgery).
What major virulence factors are produced by salmonella?
- Salmonella pathogenicity island 1 (SPI1) is a cluster of genes that encodes over 10 distinct proteins that promote virulence and invasion. One of these is invH, a gene
encoding a surface adhesion protein. Several inv genes encode proteins important for trafficking of virulence factors.
For example, the InvJ regulator protein controls assembly of structural proteins InvG, PrgH, PrgI, PrgJ, and PrgK, which form a type III secretion system called the injectisome, an organelle in the bacterial
envelope that allows for the direct transfer of virulence proteins into
host cells through a needle-like assembly. - A second Salmonella pathogenicity island, SPI2, contains genes that are responsible for causing more systemic than localized disease and resistance to host defenses.
In which two ways do bacteria damage host tissues?
- By secreting tissue-destroying enzymes
- by secreting or shedding toxins that target specific host tissues, or the entire host
streptococci, staphylococci, and certain clostridia produce the virulence factor hyaluronidase. How does it work?
Hyaluronic acid is a component of the extracellular matrix and functions as a type of ‘intracellular cement’, helping to maintain the organization of individual cells into tissues. The activity of hyaluronidase causes host cells to slough apart, allowing pathogens at an initial colonization site to spread between host cells to attack subsurface tissues.
Which bacteria typically produce hyaluronidase and streptokinase, and which produce coagulase?
- Virulent strains of Streptococcus pyogenes typically produce hyaluronidase and streptokinase.
- Virulent strains of Staphylococcus aureus typically produce coagulase
What does streptokinase do and how can it increase the pathogenicity of a bacterium?
Streptokinase dissolves fibrin clots (on wounds) to make further invasion possible. Streptokinase specifically activates
the host to produce plasmin, an enzyme that degrades fibrin blood clots. This enables the pathogen to be released into the bloodstream and deepter tissues.
What does the enzyme coagulase do?
Coagulase promotes the formation of fibrin clots by converting fibrinogen to fibrin, resulting in the clotting of blood and the formatin of fibrin surrounding the S. aureus cells. This blanket of fibrin protects the S. aureus cells from attack by cells of the host’s immune system.
Give an explanation for the localized nature of Staphylococcal infections. (As seen in boils and pimples)
Because of the coagulase produced by Staphylococcus aureus, it is shielded by a fibrin blanket. This causes it to be unable to be destroyed by the immune system, but because of this blanket, it cannot go into the bloodstream or deeper tissues.
What type of infections does Enterococcus faecalis cause and how does it do this?
Virulence factors produced by the gram-positive bacterium
Enterococcus faecalis (a major cause of bacteremia, surgical wound infections, and urinary tract infections) subvert the protective role
of lysozyme in host mucosal surfaces by altering the structure of the bacterium’s peptidoglycan such that lysozyme can no longer recognize its substrate.
What is the function of IgA antibodies and how do some bacterial pathogens counter its protective role?
IgA antibodies are present in the host’s mucosal surfaces. These ‘secretory antibodies,’ as they are called, help prevent pathogen adherence to host tissues. Certain pathogenic bacteria counter this protective role by producing enzymes that specifically cleave IgA (IgAases), rendering this host defense useless. Examples: Neisseria gonorrhoeae (gonorrhea) and Neisseria meningitidis (meningitis).
What are exotoxins? What are enterotoxins and what do they cause?
- Exotoxins are toxic proteins secreted by the pathogen as it grows.
- Enterotoxins are toxic proteins whose site of action is the small intestine, causing secretion of fluid into the intestinal lumen, resulting in vomiting and diarrhea.
Into what three categories do exotoxins fall?
- AB toxins
- Cytolytic toxins
- Superantigen toxins
How do AB toxins work?
Name some examples of potent AB toxins.
AB toxins consist of two subunits: A and B.
The B component binds to a host cell surface molecule, facilitating
the transfer of the A subunit across the cytoplasmic membrane,
where it damages the cell. Examples: diphtheria, tetanus, botulism, and cholera.
Give a detailed explanation of how the AB toxin in C. diphteriae works.
- Subunit B specifically binds to a host cell receptor protein on eukaryotic cells, the heparin-binding
epidermal growth factor. - After binding, proteolytic
cleavage between subunit B and the remaining portion of the protein, subunit A, allows subunit A to move across the host cytoplasmic membrane into the cytoplasm. - Here, subunit A disrupts protein synthesis by blocking transfer of an amino acid from tRNA to growing polypeptide chains.
How is protein synthesis stopped by AB toxins of C. diphteriae? (Which elongation factor is stopped, etc)
Diphtheria toxin specifically inactivates
elongation factor 2 (EF-2), a protein that functions in growth of the polypeptide chain (EF-2 is essential for moving the ribosome along the mRNA). EF-2 is inactivated by catalyzing the attachment of adenosine diphosphate (ADP) ribose from NAD+. Following ADP ribosylation,
the activity of the modified EF-2 decreases dramatically, and protein
synthesis stops.
