Urinary Tract Infections - Pathogenesis / Microbes Flashcards

1
Q

What is pyelonephritis?

A

Bacterial infection of the kidney, causing inflammation

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2
Q

Why do UTI-causing pathogens need pili / adhesins to “reach out” to host epithelial cells?

A

The bacterial cell and epithelial cells are both negatively charged, so the repulsive forces would push them apart

Gram positive will often adhere via polysaccharides

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3
Q

What are the two leading pathogens of uncomplicated UTI?

A
  1. E. coli

2. Staphylococcus saprophyticus

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4
Q

What strain of E. coli is often implicated in UTIs? Where does it come from and how is it identified in the lab?

A

UPEC - Uropathogenic E. coli

Comes from own or sexual partner’s intestinal microflora

Identified as beta-hemolytic, lac + gram negative rod.

It is oxidase negative

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5
Q

How is a UTI quantitatively determined in the lab?

A

A 10 microliter calibrated loop of urine is plated onto a blood agar plate. Each colony represents 100 CFU/mL.

> 100,000 CFU / mL = bacterial infection. 10,000-100,000 is ambiguous. <10,000 is normal contamination.

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6
Q

What are the three main types of Pili on UPEC and what is their mannose-sensitivity (unable to work when a plate it covered in it)

Which ones agglutinate RBC in the lab?

A
  1. P-pili - mannose insensitive
  2. Type 1 Pili - mannose sensitive (bind mannose)
  3. Type S fimbriae - mannose insensitive

They all agglutinate RBCs in the lab

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7
Q

What does P-pili bind and what does the name mean?

A

P-pili = pyelonephritis pili - found in 80% of pyelonephritis isolates

These pili bind globobiose, a glycosphingolipid

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8
Q

What are the functions of the P-pili?

A

Make the organism hard to phagocytose

Induce inflammation and PMN infiltration into the bladder (inducing IL-8 production, as well as IL-6 (pyrogenic))

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9
Q

What do Type 1 Pili bind? When is it expressed?

A

Mannose

Has an invertible promoter so that it is “on” in the bladder but “off” in the kidney -> expressed early in infection

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10
Q

What do Type S fimbriae bind? What are they associated with?

A

S = Sialic acid on glycoproteins

Associated with both cystitis and pyelonephritis, as well as neonatal meningitis + bactermia

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11
Q

What is the purpose of the afimbrial adhesins?

A

They recognize the Dr blood group antigen, and adhere to urepithelial surface for internalization of UPEC (evade immune response)

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12
Q

What is the purpose of the UPEC hemolysin?

A

Primarily exists for iron acquisition. It is a the mediator of kidney damage in pyelonephritis by lysing tubular cells and RBCs

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13
Q

What is the second toxin produced by UPEC?

A

Cytotoxic necrotizing factor type 1 (cnf1)

Found in about half of strains, serves to kill human bladder epithelium in apoptosis

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14
Q

What else about E. coli works synergistically with the P-pili’s inflammatory properties?

A

LPS -> induces proinflammatory cytokines like IL-8

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15
Q

What is the purpose of K antigen?

A

Capsule composed of polysaccharides - antiphagocytic

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16
Q

What is the morphology of S. saprophyticus, and who does it disproportionately cause UTI’s in?

A

Gram + cocci, disproportionately affects females (above normal UTI rates)

17
Q

What does S. saprophyticus usually cause?

A

Urethritis and cystitis, but not pyelonephritis

18
Q

What do women with UTI’s tend to have more of?

A

More mannose receptors, for binding of Type 1 pili, as well as globobiose for binding of P-pili

19
Q

Does S. saprophyticus have a hemolysin?

A

Yes, but it is not found in all strains. Goes along with the hemagglutinin virulence factors

20
Q

What is the protein on the outside of S. saprophyticus?

A

Ssp = Saprophyticus surface-associated protein

21
Q

What are kidney stones and how does S. saprophyticus promote their formation?

A

Struvite stones - magnesium ammonium phosphate

They have a urease which hydrolyzes urea to give ammonium ions, alkalizing the urine and promoting stone formation

22
Q

What is the most common way to get S. saprophyticus?

A

Autoinfection from colon

23
Q

How is S. saprophyticus identified in the lab?

A

Grows on CNA agar (Gram positive), is catalase + (it’s Staph), catalase negative (not aureus), and novobiocin-resistant

24
Q

What is the morphology of K. pneumoniae and how can it be told apart from E. coli? How does this relate to its pathogenesis?

A

Gram negative rods forming mucoid colonies. Also lac+

It is non-hemolytic -> it is more often seen in patients with underlying disease

25
Q

What two fimbriae does K. pneumoniae have?

A

Type 1 fimbriae -> mannose-sensitive like E. coli

Type 3 fimbriae -> mannose-resistant

26
Q

What other virulence factors does K. pneumoniae have?

A
  1. Capsule - bilayered and antiphagocytic
  2. LPS
  3. Urease - induces stone formation
27
Q

Where is K. pneumoniae normally found?

A

The colon

28
Q

How is Proteus mirabilis told apart from K. pneumoniae or E. coli?

A

It is a gram negative rod, beta-hemolytic like E. coli. Big difference: LAC negative (-)

29
Q

Why is Proteus mirabilis of particular concern?

A

It is highly urease positive - to the point that you can smell it. Forms kidney stones very well

30
Q

Where is P. mirabilis most often found and who does it infect?

A

Found in the colon, often infects patients with underlying disease (like K. pneumoniae)

31
Q

Why is Proteus really good at causing pyelonephritis?

A

Has adhesions like MR/P (mannose-resistant, proteus-like) and displays “swarming” motility - it is highly motile and easily ascends via flagella through ureters to kidney

32
Q

What is PMF? Why is it different than other fimbriae?

A

Proteus Mirabilis Fimbriae

Not a hemagglutinin
Important in bladder but NOT kidney colonization

33
Q

How can Enterococcus species be told apart from S. saprophyticus?

A

It will grow in high salt conditions (6.5% NaCl) as well as Bile Esculin agar.

Also, it is catalase negative (Staphylococci are catalase positive)

34
Q

What patient population is Enterococcus commonly found in?

A

It comes from the colon, but it is seen in patients with indwelling catheters

35
Q

What is Asa1?

A

Aggregation substance, a virulence factor of Enterococcus which fascilitates conjugal plasmid exchange for antibiotic resistance, and is also involved in adherence via integrins

36
Q

What are two other virulence factors of enterococci?

A
  1. Cytolysin - lyses RBC for iron

2. Sex pheromones - function in plasmid acquisition but also trigger neutrophil attraction and immune damage

37
Q

What is on the tip of Type 1 fimbriae?

A

FimH tip - important in bladder adhesion

38
Q

What is on the tip of P-pili which infect kidney and how does it contribute to pathogenesis?

A

PapG tip - involved in antigen switching to evade immune response