Title: T4 / BV6 / Modul 5 / Bakteriella UTIs

Q: Who is more likely to get an UTI?
A: Women coz shorter urethra

Q: How prevalent are ITIs?
A: Very prevalent

What is the pathophysiology of UTIs?

Q: Where does the bcteria multiply?
A: Uretra

WHich are the main risk factors of getting a UTI?

Q: WHich constitutive passive defences do we have against UTIs?
A: - Physical barriers
- Expressed antimicrobials
- Resident immune cells

Q: What does adative immunity look like in the bladder?
A: - Dendritic cells, T-cells and B-cells
- Humoral response with antibodies against O and K antigens (IgA and IgG)

Q: Which are the main pathogens causing UTIs?
A: - Most are caused by e. coli

Q: Which bacteria cause UTIs community vs hospital?
A: More diverse in complicated

Q: How can e. coli be descirbed?
A: - Gram- bacteria
- Enterobacteria
- Found in the normal gut microbiota

Q: Which type of UTI is more complicated?
A: Higher urinary tract infections

Q: WHat can happens with UTIs worst case?
A: Can infect kidney and lead to systemic infection

Q: Which symtomes are more commonly seen in lower UTIs?
A: Burning senseation when peeing, urgency having to go more often, flank pain and tenderness - lower
- More severe symtomes of upper UTIs

Q: Of what complexity are most UTIs?
A: Uncomplicated

Q: Are hospital and community aquired UTIs caused by the same bacteria?
A: Differnet bacteria cause hospital and community UTIs

Q: What does the urothelium produce to protect from bacteria?
A: Urothelium with mucus that makes it harder for bacteria

Which early induced defences do we have against infection (UTIs)?

Q: What is exfoliation?
A: Exfoliation, whe the bacteria invades the mucus and comes down to the urothelial cells, the urothelial cells can release from the rest of the tissue and pass with urine
- They can also secrete antimicrobials

Q: Which UPEC (UroPathogenic E. Coli) groups do we have?
A: UPEC phylogroups A, B1, B2 and D

Q: How does an UPEC infection occur (steps)?
A: 1. UPEC adhesion to uroplakins on bladder urothelial cells
2. Invasion of urothelial cells
3. Clonal expansion of a single bacterium to form IBCs
4. Fluxing and filamentation of clonal population

Q: WHich strategies/virulence does UPEC have to cause a UTI?
A: - Pili can invade the cells
- They can hide from the immunsystem
- They can colonize other cells (intra) and not be detected by immune cells

Q: Which virulence factors does UPEC have?
A: - Toxins/adhesins
- Type 1 pilus
- LPS
- P-type pilus
- Flagella
- Curli
- OMPs/adhesins
- Siderophore receptors
- TonB-dependent iron-uptake rec
- Outer-membrane vesicles

Q: WHich categories can UPEC's virulence factors be divided into?
A: - Adherence
- Toxin
- Immune evasion
- Iron acqusition
- Other

Which virulence factors does UPEC harbor?

Q: WHich adhesion (virulence) factors does UPEC have?
A: Chaperone-Usher pathway pili (CUP):
- Type 1 (Fim) pili
- P (Pap) pili (pyelonephritis pili)

Q: What does UPEC use pili for?
A: UPEC has serveral pili
- They are used to attach to specific cells
- Type 1 pilus is important to attach to the umbrella cell
- The type 1pili interacts with the uroplactin which confirms it being a urothelial cell
- The flagella is used to migrate to the urothelial cells

Q: Which pilus can UPEC use in the kidney?
A: - In the kidney the UPEC can use another pilus, P-pilus
- Recognize globosides

Q: How can UPEC's pili be compared, structure-wise?
A: These pili are similar
- They are multisubunit pili that assemble from the outer membrane of the bacterium
- In the pili, the tip comprise the adhesin

Q: WHich additional function does the P-pilus have?
A: The P-pilus has an additional function, interacting with TLR-4, inhibits its signaling adn inhibit PIGR expression decreasing capacity of IgA to pass through the membrane of the kidney epithelium, less IgA goes through the epithelium and less will recognize the bacteria and prevent detection by the immune system

Q: Which factor is important for UPEC-internalisation?
A: Cytotoxic necrotizing factor 1 (CNF1)

Q: How is UPEC internalised?
A: UPEC will be internalised, one of the the main virulence factors needed is CNF1
- It allows UPEC to activate the recruitment of RHO GTPases, leads to membrane ruffling, rearranges the cytoskeleton and bacteria will be internalized
- The activation represses apoptosis, the cells even if colonised they have a tendency to survive

Q: What do UPEC use for nutrient acqusition?
A: - Siderophores for iron acqusition
- Pore forming toxin HlyA for nutrient acquisition

Q: What is needed after internalisation of UPEC?
A: - Nutrient acquisition
- Needs to grow and multiply
- UPEC can secrete virulence factors which will acqurie the nutrients

Q: How does UPEC uptake iron?
A: Iron is essential for bacterial growth, without it they can't multiply - bacteria tires to counteract this with siderophores - helps bacteria capture and internalise iron into itself

Q: What is HlyA?
A: HlyA is important for nutrient aquisistion and internalisation

Q: How does HlyA work?
A: - The subunit will interact with membrane receptors and activate PFT, which will assemble into pre-pore intermediates will them be inserted in the membrane
- This creates a pore leading to Ca2+ and other nutreints to go through this pore

Q: What else do bacteria use HlyA for?
A: Bacteria also use ths toxin to lysate the cell they are in by creating a pore in the membrane, but cells will eventually lysate bc of it

Q: How can UPEC ensure its own survival?
A: - They can stay in that form for a while, during treatment u need to do it for longer coz of the biofilm
- An important factor to form the biofilm is a pilus, called a Curli important for making the matrix of the biofilm, it is a long curly structure that forms a dense network around the bacteria

Q: What does the curli do?
A: An important factor to form the biofilm is a pilus, called a Curli important for making the matrix of the biofilm, it is a long curly structure that forms a dense network around the bacteria

Q: How can UPEC disseminate?
A: - Morphological change - filamentous
- Exfoliation dependent of HylA

Q: How do UPEC disseminate through morphological change?
A: - Bacteria disseminate from being intracellular, they are UPEC that modify their shape so they are longer - they look like filamenotus bacteria which cannot be detected by the immune system
- When undetected they can go to the next cell and start a new cycle

Q: How do UPEC disseminate through exfoliation?
A: By exfoliating it creates an
access point for UPEC to cells under the umbrella cells and target other
cells, this is one way to cause a more severe UTI and may go to the
circulation system

Q: What plays a role in the persistance of UPEC?
A: Quiescent intracellular reservoirs (QIRs)

Q: What are QIRs?
A: QIRs are UPEC that will go in the cells underneith umbrella cells and create a compartment that protect bacteria and composed fo actin, this reservoir are not metabolically active persistance and can stay in the cell for a while

Q: What is QIRs causing?
A: This is the reasons for
recurring UTIs, bc the bacteria can hide for a long time and antibiotics
won't target them, so when the treatment is done the bacteia can be revived
and a new cycle will start

How are UTI's diagnosed in women?

Q: How are UTI's diagnosed in men/children?
A: Urine culture

Q: How are UTI's diagnosed in risk patients?
A: - CRP (pyelonephritis indication)
- S-creatine (ppor kidney function)

Q: What is a problem when it comes to the treatment of UTIs?
A: Antibiotic resistance is a problem

Q: What bacterium is responsible for catheter associated UTIs?
A: - E. Coli is mostly responsible for this infection, but also enterococcus
- These only cause UTIs if the patient has a catheter because they only form biofilms on catheters

Q: What is important for proteus mirabilis (and UTI-causing bacteria in general)?
A: - MR/P pilus important for adhesion
- The bladder is a watery environment where bacteria move around a lot so they need to attach

Q: What will proteus mirabellis cause in the bladder?
A: CO2 and ammonia production form crystals that will attach to the bacterial surface, which helps bacteria form biofilm - crystal biofilm, which protects the bacteria

Q: What will the presence of crystals in the bladder cause?
A: - The presense of crystals will cause the bladder having trouble to be emptied completely
- The infection will stay longer and can spread to the kidneys

Q: What does HpmA from proteus mirabilis cause?
A: HpmA toxin leads to the lyse and exfoliation of umbrella cells

Q: How can enterococcus faecalis be described?
A: - Gram+
- Found in the gut tract
- High antibiotic resistance

Q: WHat is the main virulence factor of enterococcus faecalis?
A: Its main virulence factor is formation of biofilm on the catheter
- Has a EBP pilus
- The pathogen produces this pilus which interacts with fibrogen and the catheter wihich can form a huge biofilm

Q: How can staphylococcus saprophyticus be described?
A: - Gram+
- Found in the rectum

Q: WHich specificities of UTI does staphylococcus saprophyticus have?
A: - Lower CFU counts
- cUTI or UTI in young women
- Co-infection with candida

Q: Which virulence factor is important for staphylococcus saprophyticus?
A: The important virulence factor is Aas - adhesin
- They attach together and interact with the cell host
- There is no pilus to interact but there is an adhesin