Eschericia Coli and UTI's Flashcards
What are the 2 major classifications of UTI’s? how are they acquired?
- Uncomplicated
○ Community acquired- Complicated
○ Hospital acquired
- Complicated
What are the major symptoms and outcomes of UTI’s (both moderate and severe)?
- 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)
Explain how community acquired UTI’s occur
Either an ascending infection from urethra or downstream from blood
Why are UTI’s less common in males?
Urethra is not as accessible/close to anus
What are predisposing factors that increase the risk of community acquired UTI’s?
- 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)
What are potential risk factors for Uncomplicated and Complicated UTI’s?
- Uncomplicated: Female gender, Older age, younger age
- Complicated: Indwelling catheters, Immunosuppression, Urinary tract abnormalities, Antibiotic Exposure
What is the most common bacteria in UTI’s?
UPEC
What are host defence mechanisms that aim to prevent bacterial colonization of the urinary tract (mechanical and biological processes)
- Mechanical
○ Flushing urine
○ Sphincter action
○ Epithelial cell shedding
- Biological
○ Immune systemWhat are the initial events of UPEC infection? (what are the 2 requirements)
- First requirement: Source of urinary pathogenic E.coli
- Second requirement: Entry into and colonization of the vagina and or the urethra
Explain the importance of adhesion in UPEC
Adhesion important since there is constant discharge
What is the mechanism of action for different Pili? (UPEC)
- 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
What is the mechanism of action for non p-pili UPEC strains
- 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
Explain what Phase variation is (UPEC)
- 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
What are Siderophores? How do siderophores compete with the mammalian immune system and bacteria? (UPEC)
- 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
How does UPEC colonization lead to the strong inflammatory response responsible for signs and symptoms of UTI’s
LPS from bacteria cause inflammatory response as well as the P-pili on the outer surface
List and describe the different UPEC exotoxins
- 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
What are virulence factors associated with more serious UPEC infection
- Capsular polysaccharide (K antigen)
- Protects bacterium from phagocytosis and serum killing -> impaired host defence
What is a biofilm? (UPEC)
A biofilm is a cluster of bacteria attached tightly together on a surface membrane with an outer mucus membrane
Explain the sequence of events in the bladder in those with
UPEC UTI infections as well as advantages of each stage
- 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
- Invasion: Attachment of UPEC, invasion of epithelial cell, localized actin rearrangement
Why is UPEC persistence high in the bladder?
The fluxing cycle may invade and remain dormant for months making it undetected and hard to know when it is completely gone
What events lead to damage in the kidney? (UPEC)
Uptake from bladder goes into the kidney and infection occurs (more detailed in notes)
