UTI's

Question 1

UTI summary

Answer 1

robably the most common infectious diseases worldwide.
UTIs are defined as a significant bacteriuria.
UTIs are classified based on location as upper or lower UTIs (Urethritis, Cystitis, Pyelonephritis).
Most infections in this system are endogenous infections.
UTIs are most commonly caused by Enterobacteriaceae, especially Escherichia coli.
Patients present with suprapubic pain, dysuria, urinary urgency and frequency.
Clinical diagnosis is often possible and can be supported with findings of pyuria on urinalysis or
positive leukocyte esterase and nitrites on a urine dipstick test. Further evaluation with urine culture.
First-line empiric treatment options for uncomplicated cystitis include trimethoprim-sulfamethoxazole,
nitrofurantoin, and fosfomycin.
UTIs account for 40% of the cases of sepsis
- you will find leukocytes and bacteria in urine upon analysis

Question 2

uti gender preferences

Answer 2

-more common in females than males
-due to anatomical differences
-

Question 3

UTI-pathogen

Answer 3

mainly E.coli butothers can cause it too

Question 4

Model systems for UTI’s

Answer 4

-mouse models
-cell culture
-humans
-swime and many more
-consider the pros and cons of each

Question 5

UTI caused by E.coli

Answer 5

• the presence of pilli=
  -the presence of O and K surface antigens
  -the ability to produce toxins such as hemolysin and cytotoxic necrotizing factor

Question 6

siderophores

Answer 6

Siderophores: Small compounds that bind iron with high affinity to help organisms scavenge iron from the environment.
Examples in E. coli: Aerobactin and Enterobactin.
Function: Allow uropathogenic E. coli to obtain iron in iron-poor environments like the urinary tract.
Key for Growth: Efficient growth in iron-limiting conditions requires siderophore synthesis (aerobactin, enterobactin) and siderophore receptors.

Question 7

urothelium

Answer 7

-the lining of the urinary tract, found in the bladder, ureters, and urethra
-Intermediate cells in the urothelium differentiate into umbrella cells. (facet cells)

Question 8

uropathogenic E.coli - pilli

Answer 8

two types of pilli systems
-type 1 and P pilus
-type 1 is assembled Chaperone-user pathway
-Pili are made through the chaperone–usher pathway by assembling pilin subunits. Chaperone proteins stabilize the subunits in the periplasm and deliver them to the usher protein in the outer membrane. The usher assembles the subunits into a pilus and anchors it to the bacterial surface.

Question 9

major receptor for type 1 pilli : mannosylated uroplakins

Answer 9

-main structural components of the urothelium
-UPEC utilises type 1 pili, and their tip adhesin FimH, to bind the
urothelium through interactions with mannosylated uroplakins

Question 10

The Role of Type 1 Fimbriae-mediated Adhesion in UPEC Colonisation
of Uroepithelial Cell Layers

Answer 10

Type 1 fimbriae on UPEC (uropathogenic E. coli) help the bacteria adhere to uroepithelial cells in the urinary tract. This adhesion is crucial for colonization, allowing UPEC to resist flushing by urine and establish infection. The fimbriae bind to specific receptors on the cell surface, facilitating bacterial attachment and contributing to the development of urinary tract infections.

Question 11

Type 1 Pilli-mediated invasion of epithelial cells

Answer 11

Type 1 fimbriae on UPEC (uropathogenic E. coli) help the bacteria adhere to uroepithelial cells in the urinary tract. This adhesion is crucial for colonization, allowing UPEC to resist flushing by urine and establish infection. The fimbriae bind to specific receptors on the cell surface, facilitating bacterial attachment and contributing to the development of urinary tract infections.

Question 12

Formation of intracellular bacterial communities (IBC)

Answer 12

-dontbknow if this or the one before is necessary

Question 13

treating UPEC infections

Answer 13

-Inhibition of pili or pili-receptor interactions.
Reducing adhesion of bacteria to host cells provide new approaches to prevent, and even treat,UPEC infections
-

Question 14

multiplefates for UPEC interaction with the urothelium

Answer 14

Type 1 pili adhesin FimH on UPEC interacts with sugar receptors like UP1a or α3/β1 integrins, triggering actin rearrangement and internalization of the bacteria. UPEC is then taken into compartments similar to late endosomes or early lysosomes. Inside bladder cells, UPEC can remain dormant or enter umbrella cells, where it can break into the cytosol, multiply, and form intracellular bacterial communities (IBCs). Bacteria released from IBCs can then infect neighboring cells.

Question 15

UPEC interactions with components of the host innte immune system

Answer 15

-causes immflamation

Question 16

pro mirabillis

Answer 16

-Proteus mirabilis causes catheter-associated urinary tract infections by forming crystalline biofilms on catheter surfaces. After entering the bladder, it invades urothelial cells within 0.5–6 hours. By 10–24 hours post-infection, P. mirabilis forms intraluminal clusters that extend through the bladder, causing urothelial cell damage, likely through toxin production or increased urine pH. Mineral deposits also form. Host immune cells, like neutrophils, are recruited to the infection site.

Question 17

p,mirabilius urease

Answer 17

-Proteus mirabilis produces urease, an important virulence
factor for this species. The enzyme hydrolyses urea to
CO2 and NH3, which initiates struvite or apatite stone
formation
-stones obstruct urine flow
-damages urinary epithelium and traps bacteria

Question 18

klebsiella

Answer 18

Klebsiella are nonmotile, rod-shaped, Gram-negative bacteria with a large polysaccharide capsule. They are commonly found in the human digestive tract without causing issues. Most Klebsiella infections occur in hospitals or long-term care facilities, with Klebsiella pneumonia and Klebsiella oxytoca being the main strains responsible for human illness. Klebsiella can infect the lungs, urinary tract, and bloodstream. Widespread antibiotic use has led to antibiotic-resistant strains, making infections harder to treat.
-Klebsiella pneumoniae is a resilient bacterium that thrives by evading the immune system rather than actively attacking it. It can grow in various host sites, surviving immune responses. In recent years, K. pneumoniae has developed resistance to many antibiotics. Two main resistance mechanisms are the production of extended-spectrum β-lactamases (ESBLs), which make it resistant to cephalosporins and monobactams, and the production of carbapenemases, which confer resistance to nearly all β-lactams, including carbapenems.

Question 19

management of UTI’s

Answer 19

• bacterial therapy = first oral and second line oral if not improvement after at least 48 hours
  -think about antibacterial resistance
  -patients advised to drink plenty of fluids to avoid dehydration
  -D-mannose, cranberry or urine alkalinising
  products may be used as self-care
  treatment strategies, however the benefit
  of these products for the prevention and
  treatment of UTIs has not been fully
  established.