VL7: Quorum sensing Flashcards
What is the literal definiton of quorum?
What is QS?
the minimum number required for a valid meeting
QS is a process of cell-cell communication
What are 2 basic benefits of QS and hoe can we use them?
- Bacteria share information about cell density and adjust gene expression accordingly
- Bacteria can express expensive processes as a collective to maximize impact on the host
-QS inhibition can be used in antibacterial therapeutics
Explain the concept QS and AI (2,4)
QS= Quorum sensing:
- Bacteria sense number of similar bacteria locally
- can take action in response
AI= Autoinduction
- Bacteria export signal molecules into environment
- Bacteria re-import the signal molecule- causes reaction
- More bacteria locally = more molecules to import
- Autoinduction - positive feedback- produce more signal
Is QS an example of altruism?
Why do something costly that benefits others? (cheaters can still benefit)
Why communicate? gives host information, false information?
Clonal reproduction- the others have the same gene so it makes sense to help them
Is spatial clustering important for bacteria?
yes
B often live in structured environments, neighbours are usually kin (clonal populations)
What molecules use Gram - bacteria as AI?
homoserine lactones (HSL)
What are vibrio fischeri and by what system is thir luminescence controlled?
- luminous marine bacterium
- symbiont of fish and squids
- lives in the light organs
- luminescence my help animals escape predators?
- bacteria gain nutrients and shelter
- only luminous at high cell density
- bioluminescence regulated by AI (A-acyl homoserine lactone (AHL)
- AI enters target cell and activates gene expression of bioluminescence genes
only occurs when bacteria are in the symbiotic state, otherwise AHL diffuse anway
LuxIR QS system
How does the LuxIR QS system work?
LuxI proteins: autoinducer synthases, produce acyl-HSL (AHL)=AI
AI freely diffuses through cell membrane and acumulates at high cell density
highAI concentration: binds to LuxR-like proteins (response regulator)
LuxR-AI complex binds target promotors, activates transcription
The vibrio fisher TCS QS is an example for which kind of bacteria?
gram negative
How does gram+ TCS QS work?
- AI precurser peptide is processed
- mature oligopeptide AI is exported by ABC
- oligopeptide AI accumulate with cell growth
- high AI concentration: AI detected by TCS ( on outside of cell)
- Transfer of phosphate to response regulator
- response regulator binds to specific target promotor to modulate expression
What is special about autoinducer-2?
- AI-2 is product of luxS gene (found in most bacterial species)
- can affect bacteria from same and OTHER species
Universal QS molecule???
$ general types of QS molecules
- general AHL structures (homoserine lactones)
- alkyl quinolones
- AIP (autoinducing peptides)
- AI-2 forms (autoinducer-2)
Do gram- have multiple QS?
usually yes (rule, not exception)
QS in V.harvey
S.13-15 nur lernen falls ichs in ner altklausur seh, mehr kompliziert als V.fisheri
What is surprising about V.cholerae QS regulation of pathogenicity?
Virulence gene expression and biofilm formation occur at low cell density and repressed at high cell density
it could be beneficial to be biofilm competent/express virulence genes at low concentraions in order to make early infection possible
at high cenn density beneficial to stop produce pathogenicity factors to transition back to a lifestyle adapted for external environment (bacteria are purged from host because of diarrhoea)
Briefly describe Myxococcus life cycle
at what points comes QS into play?
What do A and C signals do?
- multicellular style of life
- gram negative
- feeds on organic matter in soil and on colonies of other bacteria
During starvation: cells aggregate, form a mound, develops into fruiting bodies- develops spors
when nutrients available: spores germinate
nutrients present: svarms of cells grow an move in search of macromolecules or live prey
starvation: aggegation (some stay free)
starvation: pppGpp accumulation ->QS A-signal_ assesses starvation and induces aggregation
QS C-signal: manages cell movement -> fruiting body, initiaes sporulation
What means API?
AutoInducer Peptide
How does the AIP based agrQS system work in S.aureus (gram+)?
the agr operon is composed of 4 genes agrBDCA which encode the entire AIP dependent QS signaling circuit
AIP is processed by membrane bound AgrB and secreted
extracellular AIP binds to AgrC transmembrane receptor and causes autiophosphorylation of AgrC which in turn phosphorylates AgrA to activate promotors P2 andP3
P2 promotor initiates transcription of agr operon -> more AIP (Autoinduction)
P3 promotor via RNAIII up regulates a large number of virulence factors
How/Why is competence controlled by QS?
when self concentration is high = good time to import DNA (likely homologous)
ComX=autoinducer
ComP (sensor) can bind ComX -> signal cascade
Summarize 4 different types of QS circuits
Gram negative:
1. AI synthase (IZ)-> AHL (EZ) -> Receptor AHL (IZ) -> QS regulon, AI synthase (IZ)
2,. AI synthase (IZ) -> AI (EZ) -> Hisitidine kinase (M) -> Response regulator-P -> QS regulon/AI synthase
Gram positives
1. AI synthase (IZ) -> Pro-AIP (IZ) -> Transport/process (M) -> AIP (EZ) ->Histidine kinase (M) -> Response regulator-P _>QS regulon/AI synthsaae
- AI synthase (IZ) -> Pro-AIP (IZ) -> Secretion (M) ->Pro-AIP (EZ) -> AIP (EZ) -> Transport (M) -> Receptor AIP _>QS regulon/AI synthsaae
Name 5 uses of QS in bacteria
Virulence Bioluminescence Bacterial cross talk Pigmentation Exopoysadccharide production Motility and clummping Biofilm maturation Eukaryotic organisms Secondary metabolites Sporutlation Fruiting body development
Eukaryotic host cell function (Cardiovascular effects, Immune modulation)
3 antivirulence strategies to disrupt-B QS
- Qurorum receptor antagonists
- Quroum synthesis inhibition
- Quorum quenching enzymes (degradation of QS molecules) (like lactonases, acylases ect)
How could QS interference be used to control S.aureus infections?
infection happens after antibiotic treatment when it can replicate because of lack of commensals
if QS doesnt work, it would not know that its concentrations are higher, would not increase production of virulence factors
Summary
-Bacteria talk to each other
-multiple languages (i.e. intra and interspecies communication)
Bacteria distinguish self from other
-more molecules may remain to be discovered (molecules that tell who the other is)
-QD allows bacteria to be multi cellular siimilar to higher organisms
-oppportunities for novel biotechnological applications to impede /enhance QS controlled functions
-natural anti QS strategies already exist
