Gram Negative Opportunistic Infections

Question 1

True or False:

E. coli is the most common cause of Gram(-) infections.

Answer 1

TRUE:

Normal flora E. coli can cause UTIs, bacteremia and meningitis.

GI infections are caused by specialized strains.

Question 2

Uropathogenic E. Coli

(YELLOW)

Answer 2

causes bacteriurial infection - at least 10^5 bacteria/mL are present in urine

• cystitis
• acute pylenophritis: P pili (also MR)

   Adhesin      Disease  P pili           Pyelonephritis/cystitis  Type 1 pili                        Cystitis  Prs pili                    Cystitis  S pili           Cystitis

Nonfimbrial adhesin
F adhesin Pyelonephritis
Dr adhesin Cystitis

Only Type 1 pili is MS!

Question 3

Describe the significance of P pili

Answer 3

P pili are present on strains of E. coli that are associated with pylenophritis. They mediate attachment of bacteria to the human P1 blood group globoseries Gal-Gal constitutent of glycolipids present on uroepithelial cells and erythrocytes.

P1 determinants expressed in uroepithelium of P1 individuals appear to predisposed to E. coli UTIs and pyelonephritis relative to P2 individuals.

Question 4

Describe uropathogenic E. coli chronic colonization

Answer 4

Surface adhesins can also play a role in the colonization of urinary catheters and in biofilm formation.

Formation of pods or biofilm-like structures in epithelium may contribute to persistent infections

UPEC strains can invade cells

Question 5

Additional UPEC virulence factors

Answer 5

urease

proteases, lipases, IgA proteases

hemolysis

flagella

siderophores

LPS

fimbriae

secretion systems

Question 6

Describe E. coli bacteremia pathogenesis.

Answer 6

Colonization host mucosal surface
-Pili and lectins (proteins that bind carbohydrates)

Translocation across surfaces into the bloodstream by an unknown mechanism

• UTIs (especially when urinary flow is obstructed)
• Use of indwelling devices such as intravenous catheters

Survival in bloodstream (importance of serum resistance) -K1 capsule (polysialic acid, antiphagocytic)

Question 8

What is the most important virulence factor in E. coli bacteremia?

Answer 8

LPS??

Question 9

Describe the pathogenesis of E. coli meningitis

Answer 9

Bacteria from the blood stream can cross the blood-brain barrier and survive in CSF, proliferate and cause tissue damage

Other virulence determinants include siderophores (iron scavenging molecules) and hemolysin.

Question 10

Why is Pseudomonas aeruginosa considered an obligate aerobe in clinical labs?

Answer 10

While it can grow via anerobic respiration with nitrate as an electron acceptor, or ferment arginine…

It cannot ferment sugars, so detection in blood cultures requires aerobic incubation…

Question 11

P. aeruginosa is associated with…

(BLUE-GREEN)

Answer 11

burns, catheters, implanted medical devices, eye wounds

pneumonia (ventilator-assoc.)

bacteremia (immunocompromised patients)

chronic infections in lung (assoc. w/ CF and COPD) - clearance diffficulties: limitations of current antibiotics, host and bacterial factors (biofilm-alginate slime)

Also a pathogen in many species (worms, fungus, plants)

Question 12

P. aeruginosa pathogenicity

Answer 12

LPS endotoxin (gram neg.)

pyocyanin (blue-green pigment), ROS

EC proteases (elastase, anti-CT) and phospholipase, (anti - lung surfactant and host CMs)

TS33 secreted effectors: ExoA (imhibits protein synthesis), ExoS/T (modify host cell reg proteins), ExoU (phospholipase activity within cell)

Question 13

Klebsiella pneumoniae clinical syndromes

(RED)

Answer 13

Primary pneumonia (alcoholism, diabetes, lung disease)  
    - “Red current jelly” sputum

Urinary tract and wound infections

Diarrhea by enterotoxigenic strains

Bacteremia and meningitis

Question 14

K. pneumoniae virulence factors.

Answer 14

CAPSULE:

reduced phagocytosis

reduced complement susceptibility

(mucoid colony morphology)

Question 15

Enterobacter Cloacae

(WHITE)

Answer 15

Part of the normal gut flora (member of Enterobacteriaciae)

Associated with burns, wounds, respiratory, urinary infections, and catheter associated infections.

Infection occurs in the hospital setting secondary to antibiotic therapy.

IV tubing contamination 100s patients in 25 hospitals.

Question 16

Serratia marcesens

(PINK)

Answer 16

Infections are seen secondary to broad spectrum antibiotic therapy or in association with implants

Serratia is more often associated with the respiratory and urinary tracts
less likely to colonize the GI tract
The GI tract is important reservoir among neonates

Septic arthritis

Question 17

Serratia marcesens virulence determinants

Answer 17

Serratia MS-fimbrae, proteases, siderophores, and flagellar motility (swarming motility) may be virulence determinants

Question 18

Proteus vulgaris & Proteus mirabilis

Answer 18

UTIs

Virulence determinants
Flagella (swarm motility)
P. aeruginosa, E. coli and S. marcesens also swarm
Urease production

Question 19

Acinetobacter baumanii

Answer 19

indwelling medical devices, wounds, lung infections

A non-fermenter (like P. aeruginosa)

Virulence factors: capsular polysaccharides, adhesins, proteolytic and lipolytic enzymes, and LPS

Question 20

Diagnostics

Answer 20

Colony morphology-color, shape, size of colony, smell

Growth on selective media (Pseudomonas isolation agar exploits innate drug resistance)

Biochemical tests
-fermenter? Gas producer? Oxidase reaction? Urease production? And more?

Question 21

Treatment

Answer 21

Antibiotics used will vary based on the infecting microbe (species and strain) and the site of infection.

Multi-Site Resistant Gram-Negative Bacilli Surveillance Initiative (MuGSI)

-CRE strains- Carbapenem-resistant Enterbacteriaciae
2011 outbreak at the NIH tracked patient to patient
Found in hospital reservoirs
Full story: Snitkin, Segre and colleagues
Sci Transl Med. August 2012: 4:p. 148ra116
-MDR Acinetobacter

Question 22

Prevention

Answer 22

Control of underlying compromising factors

Reduced catheter usage and increased catheter hygiene

Decontamination of medical equipment and cleaning of hospital spaces (such as operating rooms)

Handwashing and glove use!