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2. BIOL2044- Medical Microbiology > SW - UTIs > Flashcards

SW - UTIs Flashcards

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1
Q

Define Urinary Tract Infections (UTIs)

A

Urinary tract infection (UTI) refers to a symptomatic infection within the urinary tract

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2
Q

Lower UTIs vs Upper UTIs

A
  • Lower UTIs involve the bladder (cystitis) or urethra (urethritis).
  • Upper UTIs generally affect the kidneys (pyelonephritis) or ureters (ureteritis).
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3
Q

What are the major composites of urine? (5)

A
  • Urea (56%)
  • Ions
  • Amino acids
  • Phospholipids
  • Creatinine
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4
Q

Why are UTIs more common in women? (4)

A
  • Anatomy – shorter urethra, closer to the bladder.
  • Birth control – use of spermicidal agents or diaphragms can increase risk of infection.
  • Menopause – decline in circulating oestrogen, causes changes to urinary tract, more vulnerable to infection.
  • Sexual activity – more common in sexually active women.
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5
Q

How are UTIs classified?

A

Single episode or recurrent.

  • For recurrent UTIs, either a relapse by the same organisms or a reinfection with a different organism
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6
Q

Uncomplicated vs Complicated UTIs

A
  • Uncomplicated - individuals otherwise healthy, with no additional urinary tract problems
  • Complicated – associated with other factors including urinary obstruction, renal failure, urinary retention, presence of indwelling catheters, etc.
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7
Q

What are the main risk factors of the UTI? (4)

A

1) Iatrogenic/drugs

  • Indwelling catheter
  • Antibiotic use
  • Spermicides

2) Behavioural

  • Voiding dysfunction
  • Frequent or recent sexual intercourse

3) Anatomic/physiologic

  • Vesicoureteral reflux
  • Female sex
  • Pregnancy

4) Genetic

  • Familial tendency
  • Susceptible uroepithelial cells
  • Vaginal mucus properties
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8
Q

What are the stages involved in the pathogenesis of ascending urinary tract infection? (5)

A

1) Colonisation (Urethra)

2) Uroepithelium penetration (Bladder)

3) Ascension (Ureters)

4) Pyelonephritis (Kidneys)

5) Acute kidney injury (Kidneys)

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9
Q

What is the most common causative agent for both uncomplicated and complicated UTIs?

A

Uropathogenic Escherichia coli (UPEC)

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10
Q

Is urine sterile?

A

In 1950’s, Kass determined a level of 100000 colony forming units ml-1 = measure of differentiating between contamination and infection

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11
Q

What are the 3 major sequencing technologies involved in UTI detection?

A
  • Whole Genome Sequencing
  • Shotgun Metagenomic Sequencing
  • Shotgun Amplicon Sequencing
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12
Q

How are diagnositic tests used in UTIs?

A

Generally rely on chemical tests (dipstick) and bacterial culture

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13
Q

What are some key terms involved in urine diagnosis? (5)

A

Dysuria – pain/discomfort on passing urine

Polyuria – excessive urine production

Pyuria – presence of pus/white blood cells (6 – 10 neutrophils per high magnification field of view from unspun, mid-stream urine)

Haematuria – blood in urine

Suprapubic – relating to area above pubis

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14
Q

What do urniary dipsticks test for?

A

Nitrites
WBCs- Leukocytes

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15
Q

What and how are Nitrites used for in uring testing?

A

Used to test for asymptomatic infections caused by nitrate-reducing bacteria (including Gram negative uropathogens like E. coli, Enterobacter, Klebsiella, Citrobacter, Proteus)

Use the Greiss reaction: carried out in an acid medium

  • Para-arsonilic acid or sulphanilamide + NO2 –> diazonium salt
  • Diazonium salt + tetrahydrobenzoquinoline –> pink azo dye
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16
Q

What are some reasons the Nitrate test can give a false negative? (3)

A
  1. Negative in presence of non-nitrate reducing organisms
  2. Nitrate-reducing bacteria need to be in contact with reagents for long enough to get visible reaction
  3. Often bacteria are able to reduce nitrate to nitrogen, leading to false negative results
17
Q

What does leukocyte detection show in urine?

A

Can indicate an infection if present in high numbers (> 3 per microscopy field of view)

  • Test detects leukocyte esterase

BUT – infections caused by trichomonas, chlamydia and yeasts can result in this without bacteriuria

18
Q

What 3 categories do virulence mechanisms for UPEC fall into?

A
  • Adhesion – prevent removal in flow of urine.
  • Survival – able to acquire iron and can evade host defences
  • Toxicity – leads to inflammation
19
Q

What are some features related to virulence factors of UPEC? (4)

A
  • UPEC strains are opportunistic intracellular pathogens.
  • Essential to be able to bind and attach to host cells and tissues.
  • Primary adherence factors are pili and fimbriae.
  • Common adhesive organelles are type 1, P, S and FIC pili
20
Q

Describe type 1 adhesive organelles (7)

A

1) Required for colonisation, invasion and persistence (bladder).

2) Have adhesin FimH:

  • Mannosylated uroplakins
  • Α3β1 integrins

3) Start colonisation and invasion into umbrella cells.

4) Causes a signal transduction cascade – activates Rho GTPases – actin rearrangement and internalisation, plasma membrane engulfs bacterium

5) Host defences lead to exocytosis of vesicular UPEC into plasma membrane

6) Formation of transient biofilm-like intracellular bacterial communities (IBCs)

7) Also development of quiescent intracellular reservoirs (QIRs)

21
Q

What are features of P pili? (4)

A

PapG

  • Binds globosides (contain glycolipids) present in the kidneys.
  • PapG also modulates local secretory antibody immune response.
  • Interacts with Toll-like Receptor 4 (TLR4) which reduces polymeric receptor expression.
  • Affects IgA transport through cells to kidney lumen.
22
Q

What are some features of Siderophores, α-haemolysin (HylA) and Cytotoxic necrotising factor 1 (CNF1)?

A

Siderophores

  • bladder is an iron-limited environment
  • scavenge Fe3+

α-haemolysin (HylA)

  • secretes high concentration
  • causes pore formation in umbrella cells, promoting lysis and release of nutrients and iron
  • triggers exfoliation and highly expressed in IBCs

Cytotoxic necrotising factor 1 (CNF1)

  • affects actin modelling
  • causes membrane ruffling, aids internalisation
23
Q

What occurs during pathogenesis in catheter-associated UTI?

A

Proteus

1) Initial attachment due to expression of mannose-resistant Proteus-like (MR/P) pili.

2) Followed by production of urease which elevates pH.

3) EPS traps crystals – formation of crystalline biofilm.

4) If in contact with host tissues, toxins produced:

  • Haemolysin (HpmA) – inserts into cell membrane and induces pore formation.
  • Proteus toxic agglutinin (Pta) – punctures host membrane, cytosol leakage leads to osmotic stress and depolymerisation of actin filaments.

2. BIOL2044- Medical Microbiology (20 decks)

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