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LF255 - Clinical Microbiology > Lecture 8/9: Urinary Tract Infections > Flashcards

Lecture 8/9: Urinary Tract Infections Flashcards

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1
Q

What is the lining of the urinary tract?

A

Urothelium

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2
Q

Is the urine/ bladder a sterile environment?

A

No

2 studies in 2010/11 used metagenomics to reveal the microbiome of healthy adult urine

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3
Q

How does microbial immigration of the urinary tract occur?

A

From skin, faeces, vagina

Enter urethra and can ascend all the way to the kidneys

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4
Q

How does microbial elimination of the urinary tract occur?

A

Urine flow

Innate and adaptive immune defences

Having a healthy UT/ vaginal microbiome

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5
Q

What is the common bacterial load present in the urine?

A

~10^4-10^5 colony forming units per ml

(low bacterial load)

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6
Q

What is the common bacterial load present in the faeces?

A

10^12 colony forming units per gram

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7
Q

What percentage of urinary microbiota are shared with the gut?

A

62.5%

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8
Q

What percentage of urinary microbiota are shared with the vagina?

A

32%

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9
Q

What are risk factors of UTIs?

A

Female anatomy
Structural problems
Pregnancy
Catheterisation
Previous UTI
Structural problems
Compromised immune system
Sexual activity
Age
Dehydration
Changed vaginal microbiome
Uncontrolled diabetes
Poor hygiene

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10
Q

What are the defining factors of uncomplicated UTI?

A

Adult patient
Female anatomy
Functionally normal urinary tract
No fever
Not immunocompromised
Not pregnant
Sensitive to antibiotics

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11
Q

What are the defining factors of a complicated UTI?

A

Child patient
Male anatomy
Structurally abnormal urinary tract
Fever
Immunocompromised
Pregnant
Resistant to antibiotics

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12
Q

What are the symptoms of a UTI?

A

More frequent urination
Burning sensation when urinating
Urine is cloudy, darks or smells
Pain in lower abdomen
Hugh or low temperature
Children: being sick

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13
Q

What are the complications of UTIs?

A

Recurrent infections

Chronic infection

Kidney infection

Premature delivery (pregnant)

Bloodstream infection

Sepsis

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14
Q

When is a UTI considered recurrent infection?

A

> 2 UTIs within 6 months

> 3 within a year

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15
Q

What percentage of women who have had a UTI will have a recurrence?

A

20-30%

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16
Q

What is the balloon design of a catheter called?

A

Foley catheter

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17
Q

What are the short-term uses of a urinary catheter?

A

Before/ during/ after surgery

During childbirth with epidural

To deliver chemotherapy for bladder cancer

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18
Q

What are the long term uses of urinary catheterisation?

A

If the urethra is blocked

Never damage that affects urinary control

Last-resort treatment for urinary incontinence

Elective use by wheelchair users due to lack of accessible toilets

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19
Q

How can biofilms form on urinary catheters?

A

Outside or inside can get contaminated by host-associated or environmental bacteria

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20
Q

What does catheterisation trigger and what is the effect?

A

Release of fibrinogen into the bladder

This sticks to the catheter - priming it for adhesion of bacteria that have fibrinogen-binding adhesins

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21
Q

What substances can encrust the catheter surface?

A

Crystallisation of calcium and magnesium phosphate from the urine

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22
Q

What percentage of healthcare acquired infection are catheter acquired-UTIs?

A

50%

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23
Q

In 12 moths spanning 2016/17 catheter associated UTIs in NHS inpatients caused…
Excess bed days, lost QALYs, deaths, direct hospital costs

A

45,717 excess bed-days

10,471 lost QALYs

1,467 deaths

£54.4M direct hospital costs

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24
Q

What is the most common pathogen associated with a UTI?

A

Escherichia coli

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25
Q

What does uropathogenic E. Coli posses to aid with its infectivity causing UTI?

A

Flagella provides motility

Diverse array of pili allow bacteria to stick to host cells and surfaces

Forms biofilms

Alpha-haemolysin bursts host cell membranes releasing nutrients

Siderophores capture essential iron and copper from host metal-chelating proteins

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26
Q

What is the difference in effect between the type I pili and type P pili associated with E. Coli?

A

Type 1 pili facilitate attachment to bladder lining

Type P pili facilitate attachment in the kidneys, affects ability of host cells to display immunoglobulins

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27
Q

How does alpha-haemolysin assist the pathogenicity of E. Coli in UTIs?

A

Bursts host cell membranes, releasing nutrients

Action allows E. Coli to penetrate into deeper layers of the UT lining

(deeper tunnelling in urothelium)

28
Q

How do the siderophores assist the pathogenicity of E. Coli in UTIs?

A

Capture essential iron and copper from host metal-chelating proteins

29
Q

How many Type I pili are present on each E. Coli cell?

A

Up to 500

30
Q

How is UPEC established in the bladder?

A

Umbrella cells on bladder surface express glycoprotein

These are bound to FimH allowing E. Coli to attach and invade cells

Invading bacterium divides into biofilm-like aggregate

Filaments are formed which are resistant to neutrophil-mediated killing and can invade other cells

31
Q

What are the glycoproteins called that are present on the surface of the bladder urothelium?

A

Uroplakins

32
Q

What is the microbiology of S. saphrophyticus?

A

Gram-positive

Coagulase-negative staphylococci

Very common cause of uncomplicated UTI

33
Q

What are the virulence factors of S. saphrophyticus?

A

Lipoteichoic acid in cell wall and surface protein haemagglutinin allow attachment to host cells

Forms biofilms using polysaccharide intercellular adhesin and various protein

Enzyme urease hydrolyses urea in urine to CO2 and ammonia

34
Q

What is the effect of urease in UTIs with S. saprophyticus infection?

A

Hydrolyses urea to carbon dioxide and ammonia

Increases urine pH and triggers crystallisation of calcium and magnesium phosphates

Leads to encrustation of catheters

Potentially urinary stones

35
Q

What is the common microbiology of P. mirabilis?

A

Motility via swimming or swarming by changing flagellar expression

Attach to host cells via fimbriae and P-like Pili

Haemolysins bursts host cell membranes releasing nutrients

Extracellular protease ZapA digests immunoglobulins and antimicrobial peptide beta-definsin

Inherently resistant to some antibiotics

Urease generates much higher urine pH - forms severe encrusting biofilms

36
Q

What is the effect of Swarmer cells in P. mirabilis?

A

Swarmer cells are more able to invade UT epithelial cells

Upregulate production of urease

37
Q

What is the effect of host cell adhesion in P. mirabilis?

A

Invades umbrella cells and forms IBCs

38
Q

What is the common microbiology of C. albicans?

A

Asymptomatic

Shifts between yeast and hyphal forms

Attaches to tissues via agglutinins and ahdesins

Express invasins which bind cadherins triggering endocytosis

Extracellular proteases and phospholipases - helps nutrients and damage host tissues

Makes biofilms

39
Q

What are the hyphal forms of C. albicans good for in UTIs?

A

Tissue invasion

40
Q

What percentage of non-catheter associated UTIs involve >1 pathogen species?

A

30-40%

41
Q

How is a UTI diagnosed?

A

Dipstick urine test

(looks for leukocytes, RBC, nitrates, pH, protein)

42
Q

What percentage of infection does a dipstick and urine culture test miss?

A

Dipstick test miss >50%

Urine culture miss ~60%

43
Q

What is the common treatment of a UTI?

A

Antibiotics, antifungals

Management of risk factors

Systematic reviews

44
Q

What can treatment failure result in for UTIs?

A

Diagnosis with painful bladder syndrome or interstitial cystitis

Bacteria hidden in bladder lining won’t get picked up in urine sample so tests can be consistently negative

45
Q

How are the protected niches formed in a UTI?

A

Host secretion of cytokines result in neutrophils and monocytes being recruited to urothelium

Apoptosis and exfoliation of urothelium leaving gaps where bacteria can invade deeper

Bacteria form quiescent IBCs that persist

46
Q

What is a standard agar plate broth made of?

A

Luria Broth

47
Q

What is present in urine?

A

Water
Urea
Sodium, potassium, chloride
Creatinine
Trace amounts of proteins
Trace amount of macromolecules

48
Q

What are the advantages of testing with synthetic urine?

A

Can be chemically designed to mimic human urine

Can change bladder cell layers and catheter material

49
Q

What are the advantages and disadvantages of mouse models used to study UTI’s?

A

Can look at dissemination of infection to other organs

Can be catheterised

(there are key differences between chemistry and organ layout)

50
Q

What are dynamic in vitro bladder models?

A

Media flows between chambers representing bladder/ waste

Controlled by pumps

Physiologically realistic physical condition (flow rate, shear forces)

Can add a catheter

51
Q

What was concluded from the Nottingham study surrounding polymicrobial UTIs?

A

1-5 bacterial species are present per sample reported by culture-based diagnostics

80% had 2 or more species

52
Q

What two bacterial species were found to occur more frequently together after being tested in a study to identify pairwise interactions between UTI isolates?

A

Enterococci and E. Coli

53
Q

What two bacterial species both express factors that promote coadherence in a UTI?

A

Candida albicans and Streptococcus agalactiae

Helps both species associate with bladder urothelium

54
Q

What is an example of UTI cross-feeding?

A

Enterococcus faecalis releases the non-proteogenic amino acid ornithine during biofilm growth in iron-limited conditions

Ornithine induces production of the siderophore enterobacterin by E. Coli, allowing it to overcome iron restriction

55
Q

What is an example of UTI competition?

A

Some clinical isolates of E. faecalis produce a bacteriocin that can lyse Gram-positive bacteria

56
Q

What is an example of UTI cross-protection?

A

P. mirabilis mostly harmed other isolates in the absence of antibiotics

Mostly protected other isolates in the absence of antibiotics

57
Q

In the presence of urea […] produces urease

A

Proteus mirabilis

58
Q

What is the effect of increased pH of urine?

A

Viability of pathogens is reduced

59
Q

What is the effect of P. mirabilis combined with providencia stuartii?

A

Helps another pathogen associated CAUTI

Intrinsically resistant to several commonly-used antibiotics

Forms biofilms

Produces urease

60
Q

What is a reservoir for many UTI pathogens?

A

The gut

Bacteria in faeces can colonise the UT via perineum

61
Q

What is the mechanistic pathway of how gut dysbiosis can lead to UTI?

A

Antibiotic use leads to gut inflammation

Causes increased nitrate availability in the gut

Facilitating overgrowth of E. Coli

Bigger reservoir for UTI

Bigger chance of clones with phenotypes necessary for UT invasion being present

62
Q

What is bacterial vaginosis caused by?

A

Inflammation caused by bacterial overgrowth

Can result from antibiotic use or hygiene practices

63
Q

What is the microbiology of Gardnerella vaginalis?

A

Normal vaginal flora but often species that overgrows during BV

Invades the bladder, induces apoptosis of umbrella cells, which form the top layer of the bladder epithelium, damaging the epithelium

Triggers reactivation of latent E. coli reservoirs in bladder cells

Caused kidney inflammation making kidneys more susceptible to E. Coli

64
Q

What do Lactobacillus species do in the vagina?

A

Help stop E. Coli colonising the vagina

Stopping it from becoming a reservoir for UTI pathogens

65
Q

What has been suggested as part of a treatment plan for preventing UTI recurrence?

A

Probiotic preparations of Lactobacillus

66
Q
A

LF255 - Clinical Microbiology (10 decks)

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