Urinary Tract Infections - Pathogenesis / Microbes Flashcards
What is pyelonephritis?
Bacterial infection of the kidney, causing inflammation
Why do UTI-causing pathogens need pili / adhesins to “reach out” to host epithelial cells?
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
What are the two leading pathogens of uncomplicated UTI?
- E. coli
2. Staphylococcus saprophyticus
What strain of E. coli is often implicated in UTIs? Where does it come from and how is it identified in the lab?
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
How is a UTI quantitatively determined in the lab?
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.
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?
- P-pili - mannose insensitive
- Type 1 Pili - mannose sensitive (bind mannose)
- Type S fimbriae - mannose insensitive
They all agglutinate RBCs in the lab
What does P-pili bind and what does the name mean?
P-pili = pyelonephritis pili - found in 80% of pyelonephritis isolates
These pili bind globobiose, a glycosphingolipid
What are the functions of the P-pili?
Make the organism hard to phagocytose
Induce inflammation and PMN infiltration into the bladder (inducing IL-8 production, as well as IL-6 (pyrogenic))
What do Type 1 Pili bind? When is it expressed?
Mannose
Has an invertible promoter so that it is “on” in the bladder but “off” in the kidney -> expressed early in infection
What do Type S fimbriae bind? What are they associated with?
S = Sialic acid on glycoproteins
Associated with both cystitis and pyelonephritis, as well as neonatal meningitis + bactermia
What is the purpose of the afimbrial adhesins?
They recognize the Dr blood group antigen, and adhere to urepithelial surface for internalization of UPEC (evade immune response)
What is the purpose of the UPEC hemolysin?
Primarily exists for iron acquisition. It is a the mediator of kidney damage in pyelonephritis by lysing tubular cells and RBCs
What is the second toxin produced by UPEC?
Cytotoxic necrotizing factor type 1 (cnf1)
Found in about half of strains, serves to kill human bladder epithelium in apoptosis
What else about E. coli works synergistically with the P-pili’s inflammatory properties?
LPS -> induces proinflammatory cytokines like IL-8
What is the purpose of K antigen?
Capsule composed of polysaccharides - antiphagocytic
What is the morphology of S. saprophyticus, and who does it disproportionately cause UTI’s in?
Gram + cocci, disproportionately affects females (above normal UTI rates)
What does S. saprophyticus usually cause?
Urethritis and cystitis, but not pyelonephritis
What do women with UTI’s tend to have more of?
More mannose receptors, for binding of Type 1 pili, as well as globobiose for binding of P-pili
Does S. saprophyticus have a hemolysin?
Yes, but it is not found in all strains. Goes along with the hemagglutinin virulence factors
What is the protein on the outside of S. saprophyticus?
Ssp = Saprophyticus surface-associated protein
What are kidney stones and how does S. saprophyticus promote their formation?
Struvite stones - magnesium ammonium phosphate
They have a urease which hydrolyzes urea to give ammonium ions, alkalizing the urine and promoting stone formation
What is the most common way to get S. saprophyticus?
Autoinfection from colon
How is S. saprophyticus identified in the lab?
Grows on CNA agar (Gram positive), is catalase + (it’s Staph), catalase negative (not aureus), and novobiocin-resistant
What is the morphology of K. pneumoniae and how can it be told apart from E. coli? How does this relate to its pathogenesis?
Gram negative rods forming mucoid colonies. Also lac+
It is non-hemolytic -> it is more often seen in patients with underlying disease
What two fimbriae does K. pneumoniae have?
Type 1 fimbriae -> mannose-sensitive like E. coli
Type 3 fimbriae -> mannose-resistant
What other virulence factors does K. pneumoniae have?
- Capsule - bilayered and antiphagocytic
- LPS
- Urease - induces stone formation
Where is K. pneumoniae normally found?
The colon
How is Proteus mirabilis told apart from K. pneumoniae or E. coli?
It is a gram negative rod, beta-hemolytic like E. coli. Big difference: LAC negative (-)
Why is Proteus mirabilis of particular concern?
It is highly urease positive - to the point that you can smell it. Forms kidney stones very well
Where is P. mirabilis most often found and who does it infect?
Found in the colon, often infects patients with underlying disease (like K. pneumoniae)
Why is Proteus really good at causing pyelonephritis?
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
What is PMF? Why is it different than other fimbriae?
Proteus Mirabilis Fimbriae
Not a hemagglutinin
Important in bladder but NOT kidney colonization
How can Enterococcus species be told apart from S. saprophyticus?
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)
What patient population is Enterococcus commonly found in?
It comes from the colon, but it is seen in patients with indwelling catheters
What is Asa1?
Aggregation substance, a virulence factor of Enterococcus which fascilitates conjugal plasmid exchange for antibiotic resistance, and is also involved in adherence via integrins
What are two other virulence factors of enterococci?
- Cytolysin - lyses RBC for iron
2. Sex pheromones - function in plasmid acquisition but also trigger neutrophil attraction and immune damage
What is on the tip of Type 1 fimbriae?
FimH tip - important in bladder adhesion
What is on the tip of P-pili which infect kidney and how does it contribute to pathogenesis?
PapG tip - involved in antigen switching to evade immune response
