6

Question 1

Invasive Bacterial Pathogens

Answer 1

Salmonella spp. Shigella spp.
• Large Intestine
• Small Volume of Stool
• Bloody Stool
• Leukocytes in Stool
• Tissue Ulcerations

Question 2

Toxin-Producing Bacterial Pathogen

Answer 2

Vibrio spp. (but primarily V. cholerae) Entertoxigenic E. coli (ETEC)
• Small Intestine
• Copious Amounts of Watery Stool
• No Blood in Stool
• No Leukocytes in Stool • No Tissue Damage

Question 3

“Hybrid” Misfits

Answer 3

Enterohemorrhagic E. coli (EHEC) Enteropathogenic E. coli (EPEC)
• LowerSmallIntestine/UpperLargeIntestine
• Colonizationcausesattachingandeffacinglesion • Bloodinstool(andpossiblyinurinewithEHEC)

Question 4

Vibrio

Answer 4

V. cholerae, etc.

Question 5

V. cholerae

Answer 5

diarrhea, “cholera gravis”

Question 6

V. parahaemolyticus

Answer 6

diarrhea

Question 7

V. vulnificus

Answer 7

tissues and blood

Question 8

V. alginolyticus

Answer 8

tissues and blood

Question 9

2 cholera types

Answer 9

el tor, classical

Question 10

A “new” El Tor strain emerged in 1992

Answer 10

Mutated the O1 antigen
• O139, a new LPS serotype
• O139 is also encapsulated
• An epidemic that affected all age groups • About 1 in 20 infected developed cholera

Question 11

Virulence factors: cholera

Answer 11

Flagella
• Pili to adhere to mucosal tissue
– Shift from saltwater to reduced ion levels found in body leads to expression of pili and to the toxin
• Cholera toxin - phage encoded

Question 12

Vibrio

Answer 12

Ctx causes transfer of ADP from NAD to activate Gs.

Question 13

ETEC

Answer 13

(the other cause of secretory diarrhea)

Question 14

E. coli

Answer 14

There are thousands of different strains of E. coli. Many are commensals, but some are pathogenic. It’s difficult to distinguish between these based on culture characteristics.
•Secretory diarrhea (ETEC, EPEC) •Dysentery-like (EHEC)
•Urinary tract infections (UPEC)

Question 15

ETEC: Enterotoxigenic E. coli

Answer 15

Responsible for 30-45% of cases of traveler’s
diarrhea (when travelling to Mexico)
• Large infectious dose
• Colonization factor antigens (cfa) on fimbrae help to adhere to mucosal tissue.
• Produces 2 toxins that are responsible for the disease:
– Heat-labile toxin(LT) – Heat-stable toxin (ST)

Question 16

Identification of Secretory Diarrhea Agents

• Rule out Vibrio cholerae

Answer 16

Have eaten shellfish or been in an endemic area – Thiosulfate-Citrate-Bile-Sucrose (TCBS) agar
– Agglutination test (El Tor strain)
– Serological Testing

• Inoculateplateswithdilutedstoolsamples
• Not very rich medium, so fastidious G- won’t grow
• Aerobicincubationkillstheanaerobes

Question 17

Treatment for Secretory Diarrhea

Answer 17

Oral rehydration
– Mix of sugar and salt

• Antibiotics can help shorten duration or reduce the severity
– Tetracyclines for Vibrio infections • E.g., doxycycline
– 2nd generation flouroquinolones for ETEC • E.g., ciprofloxacin

Question 18

Vibrio infection drug

Answer 18

tetracyclines (doxycycline ex)

Question 19

ETEC drug

Answer 19

2nd gen flouroquinolones

Question 20

EPEC - enteropathogenic E. coli

Answer 20

Prevalent in newborns
• Noninflammatory secretory diarrhea
• Distal small intestine
• Large infectious dose
• Absence of traditional exotoxins
• Characteristic intimate adherence pattern (a.k.a. an attaching and effacing lesion)

Question 21

Intimate Adherence

Answer 21

(a.k.a. an attaching and effacing lesion) by EPEC and EHEC

Question 22

Stage 1 intimate adherence

Answer 22

Bundle-forming pili (Bfp) assist in adherence from relative long distance

Question 23

Stage 2 intimate adherence

Answer 23

Syringe-like secretion system (called type III secretion) injects Tir into host cell

Question 24

Stage 3: intimate adherence

Answer 24

Tir binds to intimin on E. coli resulting in pedestal formation.

Question 25

What causes the diarrhea? EPEC

Answer 25

there is no toxin production | • Malabsorption due to microvilli disruptions • Disruption of epithelial tight junctions

Question 26

Enterohemorrhagic E. coli

Answer 26

Has set of EPEC genes (called eae genes), so it produces an attaching effacing lesion. • Also produces toxin that can lead to hemolytic uremic syndrome (which is much more serious).

Question 27

Enterohemorrhagic E. coli (EHEC)

Answer 27

• The notorious E. coli O157:H7 is the most common • Cattle are the primary reservoir • Causes an attaching effacing lesion (gastroenteritis) • Produces a shiga-like toxin – Hemorrhagic colitis – Hemolytic uremic syndrome (HUS) • 250-500 deaths each year (children are most susceptible)

Question 28

Shiga-like toxins

Answer 28

Mucosal surfaces are heavily vascularized. Shiga-like toxins attack small blood vessels of the large intestines. This can be intensified when inflammatory cytokines are present.

Question 29

EHEC

Answer 29

cannot ferment sorbitol, usually | • Detection of Shigalike toxins

Question 30

Treatment EHEC

Answer 30

Controversial, but CDC says no antibiotics! – Why? • Supportive therapy—rehydrate if necessary, usually not necessary. • Dialysis if HUS is pending

Question 31

cystitis.

Answer 31

Inflammation in the bladder

Question 32

uncomplicated UTI

Answer 32

All normal defense mechanisms are intact – No recent hospital admissions – Disease limited to lower urinary tract

Question 33

complicated UTI

Answer 33

Some structural abnormality in urinary tract – Recently admitted to hospital – Disease most likely will spread to kidneys

Question 34

Natural Defenses Found in Urinary Tract

Answer 34

``` Complete voidance of bladder Peristalsis Ureterovesicle valves Mucous layer Normal microbiota (e.g. Lactobacillus spp.) pH ```

Question 35

UTI can spread to kidney and cause

Answer 35

pyelonephritis Retrograde flow of urine from bladder to kidneys • Neurological disorders leading to poor emptying of the bladder • Children—incomplete closing of the ureterovesical valves • Pregnancy—hormones cause dilation and decreased peristalsis of the ureters

Question 36

Urinary tract stones—some

Answer 36

bacteria, like Proteus spp. neutralize pH of urine and cause the formation of “struvite” calculi (insoluble precipitate that can damage vesicles)

Question 37

UPEC Uropathogenic E. coli

Answer 37

Can adhere to uroepithelial cells through fimbriae. – Acute cystitis (i.e., uncomplicated UTI) associated with fimbrial antigen FimH – Pyelonephritis is associated with expression of P fimbriae • Production of aerobactin and hemolysin (associated with pyelonephritis) – Hemolysin has the ability to lyse host cells • Geneticlinktorecurrentdisease – Could be linked to ABH non-secretor status in older women, not in younger women

Question 38

Proteus mirabilis is an

Answer 38

additional cause of uncomplicated | UTI

Question 39

• P. mirabilis

Answer 39

Occurs in uncomplicated and nosocomial infection, abnormal urinary tract structure more likely to have UTI caused by P. mirabilis – P. mirabilis UTI tends to be more severe than an E. coli induced UTI

Question 40

Proteus mirabilis virulence | factors

Answer 40

Flagella Anadhesinonthefimbriaeisspecificforurinary epithelium (exact adhesin is not known) • Hemolysins • IgAprotease • Urease,anenzymethatraisesthepHofurine – Urea → 2NH3 + CO2 – Bacteria will grow better in the less acidic environment – Toxic to renal cells – Enhances formation of struvite (magnesium ammonium phosphate) urinary stones, which can lead to a chronic infection

Question 41

Diagnosis Proteus mirabilis

Answer 41

* Surprisingly difficult to positively ID the causative agent of a UTI * Count bacteria in the urine * Healthy (asymptomatic) individual bacteriuria ≥ 105 CFU/ml * Individual with dysuria ≥ 102 (with pyuria) * Proteus can be diagnosed by: • Consistently alkaline urine • Production of urease

Question 42

Treatment proteus mirabilis

Answer 42

A variety of antimicrobials • Trimethoprim-sulfamethoxazole (TMP/SMX) first choice – 3 day therapy for acute cystitis – 10-14 day therapy for polynephritis – Prophylactic treatment – Asymptomatic bacteriuria • Pregnant females

Question 43

Klebsiella

Answer 43

Large, mucoid colonies due to large capsule -- pneumonia

Question 44

Klebsiella virulence factors

Answer 44

Pili – Type 1 pili important for adherence to urinary tract epithelial cells – Type 3 pili important for adherence to respiratory tract epithelial cells • Enterotoxin similar to ST and LT (so, they can induce secretory diarrhea). • Aerobactin-an iron sequestering protein • Antiphagocytic capsule – Thought to be the primary virulence factor. Why?

Question 45

Helicobacter pylori

Answer 45

* Among the most prevalent Gram-negative GI bugs * Unlike other GI bugs we’ve studied, this is believed to be transmitted through oral-to-oral contact (as well as fecal to oral) * It is a “slow” bacterium * In the gi tract, only found in the mucous overlying mucous secreting cells of the stomach * An animal reservoir for H. pylori has not been found

Question 46

Multiplication and Pathogenesis - helicobacter pylori

Answer 46

Readily killed by gastric acid • Efficient producer of urease • Inflammatory effector molecules—cause epithelial cells to produce IL-8 • Cytotoxin is associated with peptic ulcer disease (induces vacuolation and apoptosis of epithelial cells) • Downregulation of somatostatin-producing D- cells

Question 47

Treatment helicobacter

Answer 47

Intense with many side effects First Line • Proton pump inhibitor • Antibiotic cocktail • usually clarithromycin and metronidazole or amoxicillin • 250-1000 mg twice a day for 7-10 days Second Line • Proton pump inhibitor • bismuth subsalicylate • tetracycline 500 mg four times a day for 14 days • metronidazole 500 mg three times a day for 14 days