9-10 Bacteria: Gram- Flashcards
Components of a gram- bacterium
Cytoplasma
Phospholipid bilayer with protein
Periplasm (Peptidoglycan)
Lipoproteins connected with Outer membrane
OmpA, OmpF/C through outer membrane
Enterobact. Common Antigen (only common in Enterobacteriacae), LPS and Capsular Polysaccharide (not always) VF
PAMPs and DAMPs
What’s that + receptor ?
Example of PAMP and receptor ?
What’s the difference ?
Pathogen associated molecular pattern bound by Pathogen recognition receptors like LPS by TLR4
DAMPs is danger associated molecular patterns
Difference
PAMPS from pathogens to recognize infection
DAMPs danger signals from host cells like ROS, dying cell products etc. but also induce an inflammatory response e.g. cancer, autoimmune disease etc.
Correlation of microbial threat with inflammatory responses
soluable microbial components or dead microorganisms
low repsonses, recongnition and production of proinflammatory responses
Viable microorgansims
greater response, NLRP3 inflammasome activation > IFN-Gamma, IL-1-beta
Pathogens
even greater response
recognition to virulence receptors, cell death, ….
LPS
2 forms
Chem. Structure Pathogenicity
R-Form LPS (rough -> hydrophobic)
Lipid A (always)
conservative in structure, can be virulence factor
Core Region
short sugar part, Heptoses, Hexoses …
decreased level of conservation
S-Form LPS (smoth colony -> hyrophil)
additional Polysaccharide chain
O-Antigen, Capsule or Enterobacterial Common Antigen
not conservative
Pathogenicity
2 Phosphate groups, 2 sugars and fatty acid groups (ester and amide bound)
Amount of fatty acid groups in important for pathogenicity
LPS binds to TLR4/MD2, but can only bind with the right asymetric fatty acid structure, but symetric LPS would just bind and no dimerization would occur
Enterobacteriacae
1. Species
2. Disease
3. Kaufmann White Scheme
4. Salmonella antigens
5. most dangerous Salmonella
6. Therapy of 5.
7. Can people be asymptomatic ?
- Salmonella, E. coli, Shigella, Yersinia
- Gut and digestive system
- serotype scheme based on somatic O (LPS) and flagellar H antigen
- O antigen (LPS), H (flaggelar) and Vi (capsule)
- typhi which is capsulated invades epithelium, Gastroenteritis, can later lead to sepsis
- Antibiotics (Ampicillin) and Vaccines (Typhoid conjugate vaccine)
- Yes, e.g. Thyphoid Mary that sheds bacteria from gall bladder
Virulence factors of Salmonella (9)
fimbriae
adherence
Flagella
motility to get in the gut
Enterotoxin
diarrhea
Siderophores
iron
Antiphagocytic proteins
O-Antigen
inhibits phagocytosis
Virulence plasmid
Pathogenicity islands 1/2
LPS with toxic Lipid A
Type 3 secretion system
Injection of effector proteins via tunel
Salmonella Mechanism of infection
Other defensive mechanisms
- Uptake via food
** Salmonella pathogenicity island 1** - Adherence to epithelium via proteins
- Invasion of cells
Trigger mechanism: type 3 secretion system (homologous to flagellum): Inject effector proteins > Host cell actin rearrangement > membrane ruffling
Salmonella containing vacuole moving into Golgi direction with Dynein, Kinesin, replication:
Produces Salmonella induced factors
- inflammatory reaction
- Replication
- Apoptosis and release
Salmonella pathogenicity island 2 - Local inflammation and hematogenic spread
- DC involved
- Systemic infection leads to sepsis (LPS)
No antibodies really protect against salmonella
B cell deficient mice are more susceptible
Salmonella defensive mechanism
No recognition by PRRs > no release of proinflammatory cytokines at first
No oxidative burst
Detoxifying lysosome that prvent fusion
Inhibition of recognition through t cells via IL10
E. coli
1. General
2. Disease
3. Typing
4. Groups
5. How it become pathogenic
- Motile, non-fastidous, facultative anaerob, bile tolerant, ferments lactose
- UTIs, diarrhea,
- O (LPS), H (flagellar) , K (capsule), F (fimbrial) antigens
- Extraintestinal and Intestinal E. coli
or
Enteric disease EHEC
Urinary tract UPEC
Sepsis: MNEC - Aquiring new genetic elements via Transposon, Pathogenicity islands, phages or plasmids via deletions, point mutations or rearrangements
UPEC virulence factors and mechanism
Treatment
Virulence factors
- Contamination of vagina: E. coli moves to bladder against urine stream through fimbria
- Adherence of uroepithelial cells by type 1 fimbriae
- Invasion and multiplication in cell
- Apoptosis
- to kidney
- cytokines
- Haemolysin damages epithlium
- E coli crosses barrier > Bacteraemia
Specific antibiotics but also things like Vitamin C helps to weaken attachement of fimbriae to host cells
Virulence factors
P-fimbria, colonization factors, capsule, LPS
How does EHEC invade cell ?
- EHEC type 3 secretion system releases effector molecules Tir and EspFu
- Tir intercalates into host membrane and together with Intimin works as anchor for EHEC to attach (Tir effector proteins)
- EspFu leads to recruitment of eukrayotic proteins which lead to actin reaarangement leading to lesions of epithelial barrier
Shigella
1. Whats’s special
2. Mechanism
- It’s not motile, but very low cell count leads to infection, systemic infections mostly, only poor hygiene region, antibiotic treatment needs to start fast, not self limiting
- Attachement and invasion similar to Salmonella:
Invasion, getting through epithelium and taken up by macrophages, no fusion with lysozyme, disruption of macrophage, systemic infection.
Then can be taken up again by basolaterial part of epithelial cell to infect one cell to the next, …
Shigella O-Antigen length highly differ, long O-Antigen to avoid immune system / complement system activation
short length for better exposure of T3SS
Shigella invasion
barriers
Mechanism
It has to overcome 2 barriers:
Microbiota (competition for space/nutrients, secretion of antimicrobials, …) and mucus layer
Some Shigella have type 6 secretion system which can also kill other bacteria like E.coli
Mechanism
similar to E.coli but with different proteins
type 3 secretion system > actin rearrangement > membrane ruffling > Phagosome escape > Microtubule degradation leading to actin accumulation to enter next cell
Yersinia
1. General
2. What’s special?
3. Species
4. Life cycle
- motile, but not at 37°, facultative anaerob, environment (motile) to human (non motile)
Temperature determines mode of action
- Species
pestis > plague
enterocolitica > Enterocolitis - Flea bites rats, rats do not get ill but infect humans, human - human transmission possible (droplet)
Yersinia species and mechanims to be pathogenic for humans
Virulence factors and host cell targets
pseudotuberculosis / enterocolitica
self limiting infections in the gut
this species lost O-Antigen + gained 2 Virulence plasmids
that ended in systemic Yersina pestis
Yersinia pestis:
Biofilm for flea colonization
Loss of O-Antigen
Capsule (anti phagocytosis)
other:
flagella to live in enviroment and reach host cell
Urease (acid survivability)
