Eschericia Coli and UTI's

Question 1

What are the 2 major classifications of UTI’s? how are they acquired?

Answer 1

• Uncomplicated
  ○ Community acquired
  
  • Complicated
    ○ Hospital acquired

Question 2

What are the major symptoms and outcomes of UTI’s (both moderate and severe)?

Answer 2

• Cystitis (inflammation of the bladder) (moderately severe)
• Increased frequency, urgency and pain when passing urine
• Acute pyelonephritis (fever, chills and flank pain from renal (kidney) inflammation) ( (more severe)

Question 3

Explain how community acquired UTI’s occur

Answer 3

Either an ascending infection from urethra or downstream from blood

Question 4

Why are UTI’s less common in males?

Answer 4

Urethra is not as accessible/close to anus

Question 5

What are predisposing factors that increase the risk of community acquired UTI’s?

Answer 5

• Sexual activity (woman 20-40 years)
• Urinary tract abnormalities (Girls <10 years)
• Use of diaphragm or spermicides (increase pH of vaginal fluids, changing vaginal microbiota)
• Genetic predisposition (increased density of mucosal surface receptors)

Question 6

What are potential risk factors for Uncomplicated and Complicated UTI’s?

Answer 6

• Uncomplicated: Female gender, Older age, younger age

- Complicated: Indwelling catheters, Immunosuppression, Urinary tract abnormalities, Antibiotic Exposure

Question 7

What is the most common bacteria in UTI’s?

Answer 7

UPEC

Question 8

What are host defence mechanisms that aim to prevent bacterial colonization of the urinary tract (mechanical and biological processes)

Answer 8

- Mechanical
		○ Flushing urine
		○ Sphincter action
		○ Epithelial cell shedding
	- Biological
                ○ Immune system

Question 9

What are the initial events of UPEC infection? (what are the 2 requirements)

Answer 9

• First requirement: Source of urinary pathogenic E.coli

- Second requirement: Entry into and colonization of the vagina and or the urethra

Question 10

Explain the importance of adhesion in UPEC

Answer 10

Adhesion important since there is constant discharge

Question 11

What is the mechanism of action for different Pili? (UPEC)

Answer 11

• Type 1 pili (fimbrae) are produced by most strains of E.coli and bind to mannose residues attached to uroplakins (which are secreted by uro-epithelial cells).
  ○ Uroplakins over 90% of apical surface of
  mammalian uro-epithelium
  ○ Type 1 pili has Fim H (adhesion tip), Fim zG
  and Fim F (structural proteins) as well as Fim
  A (encodes Pilus rod)
• P-pili are primarily associated with UPEC strains and recognize the same receptor using globobiose (a pap gene cluster) which encodes proteins for the synthesis and assembly of p pili
• P-pili undergo phase variation

Question 12

What is the mechanism of action for non p-pili UPEC strains

Answer 12

• Non p-pili UPEC use a variety of other adhesions such as afimbral adhesions
  ○ Receptor for Afa adhesion is unknown
  ○ Dr adhesion recognizes Dr blood group
  antigen

Question 13

Explain what Phase variation is (UPEC)

Answer 13

• Changes occur in response to multiple environmental signals such as temperature, level of glucose, concentration of certain amino acids
• May allow evasion of host immune response

Question 14

What are Siderophores? How do siderophores compete with the mammalian immune system and bacteria? (UPEC)

Answer 14

• Siderophores are proteins used to retrieve and compete for iron which is vital for bacteria
• Enterobactin removes iron from transferrin, this is intercepted by siderocalin which means bacteria have to produce alternative siderophores such as salmochelin

Question 15

How does UPEC colonization lead to the strong inflammatory response responsible for signs and symptoms of UTI’s

Answer 15

LPS from bacteria cause inflammatory response as well as the P-pili on the outer surface

Question 16

List and describe the different UPEC exotoxins

Answer 16

• A Haemolysin (HylA)
  ○ Lyses erythocytes
  ○ Contributes to inflammation, tissue injury and
  impaired immune responses
  ○ At high levels lyses host cells, at low levels
  stimulated cytokines and superoxide
  production by renal cells
  § Leads to kidney damage and
  inflammation
• Cytotoxic necrotizing factor CNF1
  ○ Modules polymorphonuclear leukocyte
  function
  ○ Facilitates UPEC survival during the cause
  inflammatory response

Question 17

What are virulence factors associated with more serious UPEC infection

Answer 17

• Capsular polysaccharide (K antigen)

- Protects bacterium from phagocytosis and serum killing -> impaired host defence

Question 18

What is a biofilm? (UPEC)

Answer 18

A biofilm is a cluster of bacteria attached tightly together on a surface membrane with an outer mucus membrane

Question 19

Explain the sequence of events in the bladder in those with

UPEC UTI infections as well as advantages of each stage

Answer 19

• Binding: binds and invades superficial epithelial cells of bladder mediated by type 1 pili via FimH
  
  • Invasion: Attachment of UPEC, invasion of epithelial cell, localized actin rearrangement
    ○ Membrane engulfs bacteria, UPEC grow rapidly and divide.
    ○ Formation of intracellular bacterial communities (IBCs)
    § Advantage: hide and survive
  • Middle IBC’s
    ○ Many biofilm properties
    § Community behaviour
    § Associated with long-term pesistence
    § Resistance to antibiotics
    § Resistance to human immune effects
    ○ Phenotypic switch, shortening of bacteria
  • Late IBC’s
    ○ Bacteria on edge of biofilm detach and differentiate into typical rod shape
    ○ Become highly motile
  • Late IBC’s and fluxing
    ○ Motile bacteria swim to edge of cell and burst out into bladder lumen (fluxing)
    Leads to spread over epithelium and reattachment at different points

Question 20

Why is UPEC persistence high in the bladder?

Answer 20

The fluxing cycle may invade and remain dormant for months making it undetected and hard to know when it is completely gone

Question 21

What events lead to damage in the kidney? (UPEC)

Answer 21

Uptake from bladder goes into the kidney and infection occurs (more detailed in notes)