Biofilm physiology and quorum sensing Flashcards
(66 cards)
Chronic bacterial infections involve…
the biofilm mode of growth: bacteria withstand the action of the immune system and tolerate the highest deliverable doses of antibiotics.
Pseudomonas aeruginosa
16% of nosocomial pneumonia cases
12% of hospital-acquired urinary tract infections
8% of surgical wound infections
10% of bloodstream infections
30% deaths in immunocompromised patients
38% deaths in intubated patients
Associated with 60% of deaths under outbreaks in burn units
Associated with 50% of deaths in the expanding AIDS population
Cystic fibrosis patients are susceptible to chronic infection, which is responsible for high rates of illness and death.
CF is the most frequent severe genetic disease among Caucasians (1:4700).
Chronic wounds (1:100 in Denmark)
With the aggressive antibiotic regime in CF patients
the bacteria are suppressed, however not eradicated in the conductive zone, whereas the remaining respiratory zone is protected from massive biofilm infection for prolonged time.
A minimum of ____ of these problematic wounds are infected with P. aeruginosa.
50%
“Quorum Sensing” (QS)
a density related process uses cell-cell signaling to coordinate expression of virulence
Principle of QS
Bacterial cells increasing in cell density, due to this level of signals increases
Quorum size is reached
The culture makes “a collective decision” and expresses QS controlled target genes
Within the steps of Biofilm formation, when is the C-di-GMP and QS processes identified
1) Reversible attachment, 2) irriverable attachment, 3) cell proliferation - C-di-GMP identified
4) biofilm maturation, 5) dissolution - QS process identified
Explain PMN attraction in biofilm formation
during biofilm maturation, PMN leukocytes have PMN attraction to the biofilm
The biofilm is surrounded by a PMN shield and outside, necrotic PMN and virulence
When the PMN shield is broken, dissolution occurs
Overall PMN attraction and destruction causes…
collateral damage to the tissue. Inflammation develops.
Name some virulence factors involved in pathogenesis, and the genes that cause these to be upregulated
elastase
exotoxins
bio surfactants
caused - PqsR, PqsE, RhIR
How many genes are regulated by QS
200 - 400 depending on the growth conditions
What activity does OdDHL have
Immunomodulatory and vasodilatory activity
Quorum sensing controlled production of rhamnolipid by Pseudomonas aeruginosa leads to what?
Rapid necrotic killing of PMNs
What can be controlled through the QS systems in P. aeruginosa
biofilm development
antibiotic tolerance
virulence
immune shielding
In vitro biofilms seems to produce only minor amounts of what?
rhamnolipids
what are rhamnolipids?
PMN leukocyte shield constituent, able to cause rapid lysis in various eukaryotic cells
What is pyocyanin?
a virulence factor that is known to cause death in C. elegans by oxidative stress
what is PQS?
A branch of the QS, a regulatory system
genes encoding signalling molecules of the PQS are upregulated in transacriptome analysis of P. aeruginosa
LDH assay shows ____ caused by rhamnolipid
PMN leakage
What is Dynorphin A?
- Endogenous κ-agonists belonging to the opioid peptides
- Modulates pain and stress signals
- Found in Central Nervous System
- Contained in various immune cells
- PMNs produce and release dynorphin at sites of inflammation
- Found by others to activate pqs, rhamnolipids and pyocyanine
NAme a dynorphin agonist and what it induces
U-50488 -A drug which acts as a highly selective κ-opioid agonist
induces PQS and rhamnolipids
odDHL + PQS synthesis =
PMN signal
Describe the relationship of las, rhl and pqs
las upregulates pqs which upregulates rhl; pqs links las and rhl systems
pqsA mutant is not able to…
up-regulate rhamnolipid production in response to PMN exposure.
