simon swift Flashcards
Why do bacteria need iron?
This is an essential nutrient as it has two different oxidation states allowing it to play a key role in redox reactions
These reactions are critical for processes such as nucleic acid synthesis, ATP synthesis as well as enzymes such as catalase which can be used to detoxify free radicals produced by immune cells
What makes iron difficult for bacteria to obtain?
Iron is strictly controlled by the host as it can be sequestered in erythrocytes and plasma proteins such as transferrin
There is competition with commensals for iron
The chelating enzymes of bacteria must have balanced affinity as they must bind iron tight enough to take it from host proteins but not so tight that it can’t be released to the enzymes that bacteria need it for
The immune system will also upregulate an iron defence mechanism known as hepcidin binds to ferraportin regulating the amount of dietary absorption of iron
What are the sources and relative abundance of iron?
There is a variable amount iron available from dietary sources
Erythrocytes containing hemaglobin are probably the highest source of iron in the body containing 70% of iron
Ferraportein is a protein in blood plasma which contains iron
There are also intracellular proteins like feraportein such as myoglobin, transferrin, lactoferrin and ferritin
How do bacteria acquire iron?
There may direct capture of hemaglobin through the heme receptor or remote capture if the bacteria produces toxins that lyse red blood cells allowing hemaglobin to be accessed
If other cells are lysed then siderophores such as catechole hydroxymate, yersenia bactin, salmochelan and aerobactin may cheleate iron from host proteins then attach to their receptors on the bacteria
Once bound to the receptor the TonB protein mediates transfer of iron across the periplasma and into the cytosol through use of ATP
What are the basics of a urinary tract infection?
This when bacteria infect the urinary tract these bacteria commonly cause an ascending infection where they come from the environment (typically from a faecal source)
And ascend up the urethra to cause cystitis then potentially up the ureters to the kidneys causing pyelonephritis
Although descending infection where the kidney is infected through microbes in the blood is possible
These bacteria also require attachment factors like pili to avoid being washed out of the urinary tract
How can bacterial mutants be used to study mechanisms of iron acquisition?
Genes of interest can be knocked out and then its impact on bacterial functions can be observed, in the case of iron acquisition this has been used to show there is redundancy in the bacterial iron acquisition systems
How can competition assays be used to study bacterial mechanisms of iron acquisition?
This is when an animal is coinfected with two different strains of a bacteria at the same time
The bacteria which survives can then be seen to have a survival advantage this can be used to compare different mechanisms of iron acquisition as the bacteria that have the more efficient mechanism will be more successful and out compete the other strain
How can Animal mutants be used to study bacterial mechanisms of iron acquisition?
Animals which are mutated in immune defences to the pathogen including its iron acquisition mechanism can be sued to see what immune responses are the most effective at limiting iron access to the bacteria and thereby controlling its growth
How can ex vivo experiments be used to study bacterial iron acquisition systems?
This is when something is taken out of a living organism such as blood which is experimented on this can provide some of the real world practicality of an in vivo experiment but is easier to manipulate and requires less organisms
How can human antisera-be used to study bacterial iron acquisition?
This is where human antibodies are used to study their effect on bacteria
This includes the use antibodies that block various iron uptake mechanisms to see their effect on the bacteria
How can gene expression be used to study bacterial iron acquisition systems?
Gene expression allows us to determine which genes are being used and how much, offering insight into how important each gene is, as the more critical a gene is the higher its level of expression will be
How can human conditions be used to study bacterial iron acquisition>
Genetic sequencing of these individuals can reveal novel genes that can play a role in preventing bacterial iron acquisition
What are the novel treatments for infection which target iron acquisition?
Probiotics which allow commensal bacteria to outcompete the pathogens for iron
Immunisation to bacterial iron acquisitions can result in production of antibodies that bind to proteins such as siderophores blocking their function
Anti-infectives which use a molecule which resembles iron such as gallium which is then taken up by the bacterias iron uptake mechanism allowing delivery of antibiotics etc
