A 34-year-old woman comes to the office due to fever, dysuria, and flank pain. Temperature is 37.8 C (100 F), blood pressure is 122/78 mm Hg, and pulse is 84/min. Physical examination elicits suprapubic and costovertebral angle tenderness. Urine dipstick analysis reveals positive leukocyte esterase and nitrite. A subsequent urine culture grows colonies of motile gram-negative rods demonstrating a green metallic sheen on eosin methylene blue (EMB) agar and hemolysis on blood agar. Which of the following virulence factors is most important for the development of this patient's condition?
Escherichia coli virulence factors | ||
Virulence factor | Mechanism | Presentation |
Lipopolysaccharide | Activates macrophages → widespread release of IL-1, IL-6 & TNF-α | Bacteremia & septic shock |
K1 capsular polysaccharide | Prevents phagocytosis & complement-mediated lysis | Neonatal meningitis |
Shiga toxin | Inactivates 60S ribosomal subunit, halting protein synthesis & causing cell death | Gastroenteritis (bloody) |
Heat-stable/heat-labile enterotoxins | Promotes fluid & electrolyte secretion from intestinal epithelium | Gastroenteritis (watery) |
P-fimbriae | Allows adhesion to uroepithelium | Urinary tract infection |
TNF-α = tumor necrosis factor-alpha. | ||
This patient with fever, dysuria, and flank pain has bacterial growth in the urine, findings diagnostic of a urinary tract infection (UTI). Escherichia coli, a motile, gram-negative bacillus, is the most common cause of UTI and grows well on blood, MacConkey, and eosin methylene blue (EMB) agar plates. Due to its ability to ferment lactose, E coli binds to dye in the EMB agar and produces colonies that have a distinct green metallic sheen; most strains of E coli also demonstrate beta-hemolysis on blood agar.
Varying strains of E coli have specific virulence factors that determine disease characteristics; in the case of urinary tract infections, P fimbriae (pyelonephritis-associated pili) are the primary virulence factors due to their ability to adhere to uroepithelium.
Normally, E coli is a commensal bacterium in the intestinal tract; however, it can spread from the perianal region to the periurethral regions (eg, via sexual intercourse or bladder catheterization). P fimbriae allow uropathogenic E coli to ascend into the bladder, ureters, and kidneys, leading to cystitis and pyelonephritis.
(Choice A) The K1 capsular antigen promotes bloodstream survival of E coli because its sialic acid composition is similar to human cells (ie, molecular mimicry), which helps prevent phagocytosis and facilitates invasive infections. It is the major virulence factor for E coli strains causing neonatal meningitis (not UTIs).
(Choice B) Enterotoxigenic E coli produces heat-stable (ST) and heat-labile (LT) enterotoxins in the gastrointestinal tract. ST activates guanylate cyclase, causing an increase in cyclic GMP. LT activates adenylate cyclase, increasing cyclic AMP levels. These enterotoxins lead to watery diarrhea, not UTI symptoms.
(Choices C and D) Lipid A and O antigen are components of lipopolysaccharides, which make up the majority of the outer membrane of gram-negative bacteria. Lipid A is a virulence factor that activates macrophages, leading to widespread release of inflammatory cytokines (eg, IL-1, IL-6, tumor necrosis factor-alpha), which in turn causes endothelial injury, increased vascular permeability, and septic shock. The O antigen is on the outer surface and is a variable polysaccharide used to classify gram-negative bacteria. Neither component is a major virulence factor for uropathogenic E coli.
Educational objective:
Escherichia coli is the most common cause of urinary tract infections. The primary virulence factor of uropathogenic E coli are P fimbriae (pili) which allow the bacteria to adhere to uroepithelial cells and infect the bladder, ureters, and kidneys.