VL3: Bacterial pathogenicity and surface structures Flashcards
How can commensal B become pathogenic (3)?
- Proliferation (higher nb than normal)
- Entry into normally sterile sites (e.g. blood, lungs, bladder)
- host immunity reduced
How does an organism cause disease? (briefly explain 2 ways)
- toxins or lytic enzymes (e.g. v.cholerae: cholera toxin)
- colonization (usually gastrointestinal or respiratory tract) and/or invasion of tissues
- > often is the actual disease caused by the immune response (e.g. salmonella endotoxin (LPS))
Describe the general courses a disease can take with examples
- active (incubation, illness, convalesence) (e.g. influenza)
- chronic (incubation, illness…) illness persists Malaria HIV
- Latent (incubation, illness, convalescence // latent period // illness may recur) tuberculosis
3 Ways of spreading disese
- Direct (human to human (air, sexually)
- vector (arthropodes) e.g. malaria, borrelia
- food, water e.g. v. cholerae
Summary of Kochs postulate
shows that an organism is pathogenic
- path in all diseased individuals (and not healthy people)
- isolate pathogen -> grow in culture
- reinfection causes disease (problem: immunity, dose)
- reisolate pathogen from reinfected person
What is the difference between primary and opportunistic pathogens ? (+ examples)
Primary pathogens are always pathogenic (rabies virus, malaria plasmodium, tuberculosis mycobacterium)
opportunistic pathogens are only pathogenic in susceptible people (candida, pseudomonas aeruginosa) present everywhere not usually pathogenic, only at some places in body, skin infections after burn injuries or lungs in CF
2 differences in host range in diffrent bacteria
ex. only in humans (helicobacter pylori, typically vertical transfer, mom child)
broad host range, e.coli salmonella
What is virulence and how is it defined?
The relative ability of a pathogen to cause disease
defined as mortality rate (LD50) of ability to invade host tissue (no experiments)
defined as ability to invade host tissue
Does the infectious dose correlate with virulence?
No
B with pathogenic mechanisms that depend on secreted molecules (distant action) need a higher dose for infection than b with local action
5 examples for major virulence factors
capsules endotoxins exotoxins immunoglobulin proteases enzymes that damage host tissue
Name some strategies for infection prevention and treatment
vaccines
antimicrobial drugs
hygiene
nutrition
sanitation
isolation
How do B establish infections? (6 steps)
Entry into the body Colonization Avoiding immune respose Adhesion Invasion Surviving within host cells
How do microbes invade the body?
Skin- through lesions or vectors (bites)
many B have ways to get through epithelia (cells specialized for engulfment or transport in various body openings)
3 methods to promote colonization
(requires ability to obtain food and evade immune mechanisms)
- sIgA proteases (prevents trapping of B in mucin)
- Iron acquisition (sideophores, direct uptake of host iron-carrying prot,Low level toxin production ( host cell lysis releases iron) , iron abistinece
- Synthesis of nutrient scavenging systems
3 methods to avoid the immune system
- antigenic variation of surface structurs (e.g. pilins Neisseria gonorrhoeae)
- using a coat of host proteins
- avoiding phagocytosis and complement activation (capusles and lps alterations)
Brief description of adhesion
necessary first step for invasion of host tissue but not necessary for all infections (uropathogenic e.coli)
adhesins bind to specific molecules on cell surface like pili or fimbriae
Why pili?
-pili can help to increase volume where bacteria search for cells
-they maintain a separation between bacterial cell and eukaryotic cell
Why and how do B invade host cells?
how?
- uptake by phagocytic cells
- induction of uptake in non-phagocytic cells (epitelial)
why?
- nutrition
- to hide from immune system
Strategies to survive within pahgocytes
- Listeria, Shigella get out of phagosome
- Salmonella prevents fusion with lysosome
- mycobacterium, prevents acidification
induce defense systems (deal with ROS nitrogen radicals, low pH, nutrient limitations ect)
example tuberculosis:
in pagosome: mildly acidic, (tries to prevent phagosome maturation?)
IFN-y –> maturation phagosome-lysosome: stress more acidic, lysosomal hydrolases, ubiquitin derived peptides…
tuberculosis survives by resisting acidification with serine protease, magnesium transporter and pore forming outer membrane protein
4 types of cell envolpes, 2 types of appendages
Cell Envelopes:
- capsules: for adheerece, resistance to engulfment, storage
- cell wall: potection against lysis or rupture of the cell
- outer membrane: with LPS (endotoxin)
- endospores: protected resting state
Appendages:
- Flagella- organelles for motility
- Pili: for attachment or adherece to surfaces; sex pilus used during some genetic exchange processes
What is a cell wall? What is is made out of? what is good for?
sturcutre that surrounds cell protoplast
almost all B have a cell wall (except mycoplasma)
peptidoglycan (PG) (repeating units of NAG and NAM linked by peptide bridges(L-ala, D-glu, DAP, D-ala)
- semi rigid, gives cell its shape
- protection from rupture and osmotic stress
PG: Peptidoglycan
NAG: n-acetylglucosamine
NAM: n-acetylmuramic acid
What is the difference between Gram + and - cell walls?
Gram positive (mostly cocci (staphylococci, streptococci, pneumococci, enterococci), some bacilli (bacillus, clostridia, coynebacteria)
-thick PG (10-100nm)
-90% of CW
-Single membrane
cell wall is a thick homogenous monolayer
Gram-negative (mostly bacillis (e.coli, v.cholerae, salonella, h.pylori)
-thin PG (2nm)
-20% of CW
-Inner membrane, outer membrane
-periplasmic space,
-LPS
cell wall is thin heterogeneous multilayer
How do penecillin and lysozyme work?
Penicillin works by preventing formation of a interpeptide bond in PG cell walls
lysozyme breaks glycoside bond between NAG and NAM
PG: Peptidoglycan
NAG: n-acetylglucosamine
NAM: n-acetylmuramic acid
Murein is a polymer of the peptidoglycan subunit
What are teichoic acids good for?
Teichoic acids are thought to stabilize the gram positive cell wall and may be used in adherence
Name two important properties of outer membrane of gram negative cell walls
- protects the cells from permeability of substances (including penicillin and lysozyme)
- location of lipopolysaccarides (endotoxin) which is toxic for animals
What are capsules?
capsules are composed of polysaccharides deposited outside the cell wall
discrete layers enclosing a cell or group of cells –> easiliy visible under under microscope
Name 5 functions of capsules
- Protection against phagotrophic engulfment
- Mediate adherence to surfaces
- Protection against drying
- Reserves of nutrients
- Biofilms for protection against antimicrobial agents and immune system
Briefly describe endospore formation
- Vegetative cell
- DNA becomes more dense
- Asymmetric cell division
- endospore septum grows around protoplast
- forespore formation
- exosporium synthesis (primordial cortex is formed between the 2 membranes, dehydration)
- Ca2+ incorporation, further dehydration, ext
- Maturation –> development of resistance to heat and chemicals
- Lysis of cell and release of endospore
Name some Properties of endospores
- resting dormant cells, show no sign of life (due to lack of water)
- unique surface layers not found in vegetative cells (like exosporium, cortex)
- highly resistant to heat, acids, bases, dyes, irradiation, disingectants, antibiotics…
- Not a mechanism of reproduction
- survival in deleterios environments
- one vegetative cell develops into one endospore
3 examples of medically improtant endospore forming B
- Bacillus anthracis –> anthrax
- Clostridium tetani –> tetanus
- Clostridium botulinum –> botulism
