Lecture 7 Flashcards
What are siderophores
Small high affinity iron chelating compounds
They soak up any available iron
What way can iron be taken away from invading bacteria
Most iron is inside cells and protein where invading bacteria can’t take it
Neutrophils let out lactoferrin at bacterial infection sites to lower the free fe3+ where they are and stop the bacteria in that area from using the iron to grow and make biofilm
Neutrophils can also let out siderophore binding lipocalin proteins which bind to siderophores and compete for siderophores binding with the bacteria
During bacterial infection, The liver also lets out a peptide hormone called hepicidin. This also causes a anemic (low iron) state
Name a siderophore binding lipocalin proteins
NGAL (siderocalin)
How do bacteria overcome the limiting iron due to neutrophils and the liver
They secrete siderophores which bind fe3+ stronger than lactroferrin and transferrin
Some bacteria that don’t make their own siderophores can steal or borrow them from other organisms
Hemolytic bacteria can lyse the red blood cells by secreting cytotoxic peptides. Then they use the released heme as an iron source
Some bacteria use bacterial transferring or lactroferrin receptors to take iron directly from those proteins
What do you need to do to get iron into the cytoplasm of gram negative bacteria
Since gram negative has two membranes, to get iron in it need to pass these two membranes
What is OmpF
What does it let through and not let through
It’s a porin that allows passive diffusion of compounds up to 600Da across the outer gram negative membrane
Lets in small things like glucose and amino acids
Not big things like siderophores and heme groups
What is FepB
The ferric enterobactin binding protein
It binds the siderophore ferric enterobactin to get one fe3+ molecule
What type of binding does enterobactin (ferric siderophore) do to fe
Very tightly, Octahedral bind to fe3+ through oh groups, bidentate all
How does the FEP system get iron into the gram negative bacteria
The ferric siderophore outside the outer membrane gets taken in by FepA (outside membrane)
Feb B in the inter membrane space takes the siderophore to the second membrane
FepG in the membrane has FepC and D (atpase transporter) bound to it change its oxidative state to fe2+ inside the cell
What is the structure of fepA
Very compact and no space, has a cork like thing in the middle formed by the n terminal domain looping
The outside of it is like a barrel
Only has room for the siderophore
It’s n terminal domain stick into the membrane
What does the TonB system do
System is Made up of tonB and exbB exbD (anchors for ton B)
Ton B binds nterm domain cork of Fep A (through complimentary beta sheets)
use energy from the electrochemical gradient of the inner membrane to
transport the siderophore or vitamin B12 through the outer membrane receptors (by unplugging the cork on fepA)
How does TonB know when to open the cork domain
The domains of beta Barrel in the outer membrane (fepA) are are tonB dependent transporters (has to use tonB)
At the n term of fepA (the cork domain) there is a tonB box sequence
This box sequence is bound by the c terminal domain of TONB
Once the siderophore bind to the fepA, allosteric activation makes the ton B box pull into the periplasm (and open the cork)
What is ferrichrome
A hydroxamate siderophore that is made by yeast
Has octahedral geometry when binding fe3+
What can s. Aureus bacteria do
This disease causing hemolytic bacteria can break open rbc and take the heme iron directly
Or take the transferrin iron directly
In the end this froms antibiotic resistance
What is special about heme in its free from (not bound to red blood cells)
It is toxic like fe3+
