Gram-negative opportunistic infections- UPEC

Question 1

Opportunistic infections–intro

Answer 1

Pathogens that are capable of causing disease only in compromised people
-decreased or altered immune system function, alterations in innate protective mechanisms, breach in physical barriers

these pathogens show a less-specialized adaptation to host

• cause 90,000 deaths and $5b a year in US
• many should be preventable
• need for surveillance to ID source

Question 2

General points about gram-negative oppt. infections

Answer 2

Opp. infections are increasing for the following reasons:

• increased scope of surgical txs, implants, and transplants
• increased use of indwelling devices such as catheters
• increased capacity to sustain chronically ill
• increased use of medical interventions that directly affect immune systems
• immunosuppression due to primary infection (AIDS)

found in numerous environments and survive under diverse conditions

LPS contributes to symptoms of infection
-other virulence determinants (cell-surface structures aid in colonzation of host, factors involved in nutrient acquisition, toxins and secreted enzymes)

Nosocomial infections –healthcare associated infections
-simple lack of washing hands

Most can form biofilms (dense microbial communities surrounded by an extracellular matrix)

• associated with implant and catheter-related infections
• implicated in chronic lung infections, endocarditis and UTIs
• 65% of nosocomial infections are thought to be biofilm-related
• biofilm bacteria have increased resistance to a range of antimicrobial agents compared to planktonic cells

Question 3

Uropathogenic E. coli (UPEC)

Answer 3

E. coli caused 95% of all non-hospital acquired UTIs
~60% of women in US will have at least 1 UTI and 11% experience one per year

women are more susceptible to UTI due to shorter urethra
catheters are a source of infection

Question 4

UPEC Clinical syndrome

Answer 4

Clinical Syndrome:
infection with at least 10^5 bacteria/ml in urine

Cystitis: syndrome involving dysuria, frequency, urgency, and occasionally suprapubic tenderness

Acute pyelonephritis: UTI that has disseminated to the kidney- flank pain, tenderness, fever, dysuria, freq, and urgency

Typically thought to be self-limiting; however 27-44% will experience recurrence

Question 5

UPEC Pathogenicty

Answer 5

Invasion and spread of bacteria into UT almost always associated with ascending route of infection, urethra is usually colonized with bacteria

Not all UPEC strains are equivalent - different types can elaborate different types of surface adehsions

Not all humans are equivalent in terms of susceptibility

UPEC is able to invade epithelial cells and replicate within the cells

surface adhesins help colonize urinary catheters–almost 100% of these are colonized within 3 days

Additional UPEC virulence factors are LPS, capsule, motility, and a variety of exotoxins (hemolysin)

Question 6

Bacteremia caused by E. coli

Answer 6

leading cause of nosocomial bacteremia
mechanism for how E. coli crosses from UT to blood is unknown
-most often associated with UTI in instances where urinary flow is obstructed
serum resistance is a critical trait and is correlated with production of K1 capsule
hallmark of bacteremia–systemic rxn to endotoxin or LPS
management of bacterial sepsis and accompanying endotoxic shock is difficult

Question 7

UPEC K1 capsule

Answer 7

a polysialic acid capsule nearly identical to N. mengingitidis
sialic acids are constituents of most host glycoproteins and glycolipids, which may explain the lack of immune response against E. coli K1

Question 8

Neonatal meningitis caused by E. coli K1

Answer 8

remains one of the most common neonatal pathogen and one of the leading causes of neonatal meningitis
-isolated from 20-40% of healthy individuals including newborns
-vertical transmission from mother or nursery staff
-mechanism for getting into blood or CSF not known
K1 allows to escape phagocytosis
proliferation in CSF causes inflammation and tissue damage