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Flashcards in M25: Colonization Deck (35)
1

Pathogen Colonization:

1. After pathogens enter into the body, colonization is usually the next critical step for initiating the pathogenic cycle of (endogenous / exogenous) infections.

Colonization usually involves:

a. _: pathogen specifically "sticks" to target tissues using _.

b. _: adherent pathogen _ in those target tissues.

2. Colonization factors usually qualify as _ factors, e.g., inactivating an adhesin gene often lowers _.

3. Colonization gives the pathogen a sustained presence in the host and provides access to _ and/or _ (e.g., viruses need host cell protein synthesis machinery to cause disease).

1. exogenous

a. Adherence, adhesins

b. Multiplication, multiplies

2. virulence, virulence

3. nutrients and/or host factors

2

Pathogen Colonization:
Colonization is difficult:

a. Problem #1: many potential mucosal sites for pathogen adherence are _ ("_").

Solution: pathogens produce novel _ that allow them to adhere to _.

b. Problem #2: pathogens trying to colonize the body are confronted with the _ and _ (which can make _, substances active against other bacteria).

Solution: pathogens often develop specific strategies to overcome the _ and _, e.g., colonization after normal flora numbers are reduced by _.

a. already occupied by normal flora microorganisms ('squatters rights")

adhesins
unoccupied mucosal sites

b. host defenses and normal flora, bacteriocins

host defenses and normal flora
antibiotics

3

Bacterial Adherence:

Mediated by both _ and _ interactions

specific
nonspecific

4

Bacterial Adherence:

a. Specific interactions are mediated by _, which include:

i) _ (also known as _): long proteinaceous appendages extending outwards from the bacterial surface. These structures facilitate (short / long)-range interactions that attach bacteria to host cells.

ii) _: closely-associated with the bacterial surface, these molecules participate in (short / long)-range bacteria:host interactions for attachment.

Nonspecific interactions are mediated by bacterial surface charges, _.

a. adhesins

i) Pili (fimbriae)
long

ii) Nonfimbrial adhesins
short

hydrophobicity

5

Bacterial Multiplication:

1. Important for pathogenesis since it increases the delivery of _ (e.g. _) contributing to _.

2. Contributes to _ / _ in vivo.

3. Requires physiologic _ by the pathogen.

1. soluble virulence factors (e.g., toxins)
virulence

2. survival / persistence

3. adaptations

6

The Enterobacteriaceae:

A bacterial family that uses in vivo _ and _ during pathogenesis.

These are a large collection of Gram-negative rods that share the following biologic characteristics:

a. (Obligate / Facultative) (aerobes / anaerobes).

b. Oxidase-(positive / negative) (they (do / do not) produce cytochrome oxidase, useful for classification purposes).

c. Growth on _ media using _ as a sole carbon source.

d. Growth in the presence of _, allowing isolation on _ agar.

Other "factoids" about these bacteria:

a. Often found in _.

b. Often found among normal _ and in _; species (e.g., _) can acquire virulence genes to become pathogenic for even healthy people.

c. Some can cause _ disease in compromised patients (e.g., several Enterobacteriaceae cause _ in hospitalized patients with catheters).

multiplication and adherence

a. Facultative anaerobes

b. negative, do not

c. simple bacteriologic, glucose

d. bile salts, MacConkey

a. sewage

b. GI flora, feces, E. coli

c. opportunistic, urinary tract infections

7

The Enterobacteriaceae:
Escherichia:

1) Glucose utilization (+ or +/-)
2) Lactose utilization (+, -, or +/-)
3) Sucrose utilization (+, -, or +/-)
4) Gas from glucose (+, -, or +/-)
5) H2S (+*, -, or +/-)
6) Principal diseases for "healthy" people (3)
7) Principal opportunistic diseases (2)

1) +
2) +
3) +/-
4) +
5) -
6) diarrhea, dysentery, urinary tract infections (UTIs)
7) UTIs, neonatal/childhood meningitis

8

The Enterobacteriaceae:
Salmonella:

1) Glucose utilization (+ or +/-)
2) Lactose utilization (+, -, or +/-)
3) Sucrose utilization (+, -, or +/-)
4) Gas from glucose (+, -, or +/-)
5) H2S (+*, -, or +/-)
6) Principal diseases for "healthy" people

1) +
2) -
3) -
4) +
5) +, only makes trace amounts
6) diarrhea, enteric fever (typhoid fever)

9

The Enterobacteriaceae:
Shigella:

1) Glucose utilization (+ or +/-)
2) Lactose utilization (+, -, or +/-)
3) Sucrose utilization (+, -, or +/-)
4) Gas from glucose (+, -, or +/-)
5) H2S (+*, -, or +/-)
6) Principal diseases for "healthy" people

1) +
2) -
3) +/-
4) -
5) -
6) dysentery

10

The Enterobacteriaceae:
Klebsiella:

1) Glucose utilization (+ or +/-)
2) Lactose utilization (+, -, or +/-)
3) Sucrose utilization (+, -, or +/-)
4) Gas from glucose (+, -, or +/-)
5) H2S (+*, -, or +/-)
6) Principal opportunistic diseases (3)

1) +
2) +/-
3) +
4) +
5) -
6) UTIs, bacteriemias/septicemias, pneumonias

11

The Enterobacteriaceae:
Proteus:

1) Glucose utilization (+ or +/-)
2) Lactose utilization (+, -, or +/-)
3) Sucrose utilization (+, -, or +/-)
4) Gas from glucose (+, -, or +/-)
5) H2S (+*, -, or +/-)
6) Principal opportunistic diseases (1)

1) +/-
2) -
3) +/-
4) +/-
5) +/-
6) UTIs

12

The Enterobacteriaceae:
Yersinia:

1) Glucose utilization (+ or +/-)
2) Lactose utilization (+, -, or +/-)
3) Sucrose utilization (+, -, or +/-)
4) Gas from glucose (+, -, or +/-)
5) H2S (+*, -, or +/-)
6) Principal diseases for "healthy" people

1) +
2) -
3) +/-
4) -
5) +/-
6) plague, diarrhea, lymphadenitis

13

The Enterobacteriaceae:
Principal opportunistic diseases:

Enterobacter spp. (2)

Serratia spp. (3)

Citrobacter spp. (2)

UTIs and septicemias

UTIs, bacteremias/septicemias, and pneumonias

UTIs and septicemia

14

Escherichia coli:
Biology:

Like many Enterobacteriaceae, E. coli isolates are commonly differentiated on the basis of their _, _, and _ antigens.

O, H, and K

15

Escherichia coli:
Reservoir and Transmission:

_ are the major reservoir for E. coli isolates causing human disease.

Shortly after birth, nonpathogenic E. coli colonize the human _.

These normal _ flora isolates (and/or pathogenic strains) can also be passed to other body locations (e.g., the urinary tract) from host to host via _, such as _ or _.

Depending on which set of virulence genes an isolate possesses (and host defense status), those E. coli isolates may then _ or _.

People

intestines

GI
contaminated vectors, such as food or water

cause disease
merely exist harmlessly among the normal GI flora

16

Escherichia coli:
Virulence Factors:

Fimbrial and afimbrial adhesins:

- At least 21 different adhesin types have been described for pathogenic E. coli. Some are specific for _, some for other _.

- Nearly all E. coli (including clinical isolates) produce common (type 1) _ that attach to _ receptors on host surfaces.

- Pathogenic E. coli isolates also have unique _ (e.g., the _ of ETEC) that allow them to bind to _ receptors even in colonized body sites.

Iron acquisition:

- Pathogenic E. coli must compete for _ (such as _) against normal flora and host cells.

- To do that, E. coli (and other Enterobacteriaceae) produce _, which are low molecular weight, non-protein molecules that have high affinity for _.

humans
animals

pili
mannose

pili
CFA pili
unoccupied

nutrients
iron

siderophores
iron

17

Escherichia coli:
Virulence Factors:
Toxins:

_ (_): part of outer membrane of all E. coli.

_ (_): membrane-active toxin that probably contributes to _ (among its effects, can damage _ cells)

_ (_): small, cysteine-rich polypeptide that increases intestinal _ levels to stimulate fluid/electrolyte secretion.

_: large oligomeric protein (1A and 5B subunits with homology to cholera toxins) that increases intestinal _ levels

_: large oligomeric protein (1A and 5B subunits that have no homology to LT or cholera toxins) that inactivates _ to stop host protein synthesis. _ cells (and colonic and mucosal immune cells?) are sensitive.

Endotoxin (LPS)

Hemolysin (Hly)
pyelonephritis
kidney

Heat-stable enterotoxin (STa)
cGMP
fluid / electrolyte

Heat-labile enterotoxin (LT)
cAMP

Shiga toxin (STX)
ribosomes
Kidney

18

Escherichia coli:
Intestinal Diseases (5)

Enterotoxigenic E. coli (ETEC)

Enteropathogenic E. coli (EPEC)

Enteroaggregative E. coli (EAEC)

Enteroinvasive E. coli (EIEC)

Enterohemorrhagic E. coli (EHEC)

19

Escherichia coli:
Intestinal Diseases:
Enterotoxigenic E. coli (ETEC):

1) Adherence

2) Toxins

3) Invasion

i) Cause _ in infants and travelers to regions with poor sanitation. Also cause _ (70,000 cases/year in USA).

ii) Transmitted by _.

iii) Colonize the small intestine using unique _ (_) that are plasmid-encoded.

iv) After colonizing, these bacteria multiply and produce _ and/or _, increasing intestinal fluid secretion.

1) colonization factors for adhesion (CFA), type 1 pili

2) heat-labile (LT) and heat-stable (ST) enterotoxins, endotoxin

3) none

i) watery diarrhea, food poisoning

ii) ingestion of contaminated food/water

iii) pili (CFAI, II and III)

iv) STa and/or LT

20

Escherichia coli:
Intestinal Diseases:
Enteropathogenic E. coli (EPEC):

1) Adherence

2) Toxins

3) Invasion

i) Cause infant _ in developing countries.

ii) Hallmark is formation of _ and _, visible on biopsy.

iii) A/E lesions initiate with EPEC adhering to enterocytes using the plasmid-encoded _.

iv) That initial attachment allows delivery of _ (via a type III secretion system) to stimulate signal transduction pathways. This results in formation of a "pedestal" and delivery into enterocytes of a receptor (_) for _.

v) Via intimin binding to TIR, EPEC sitting on top of the pedestal becomes even more closely associated with _.

vi) Delivery of effectors into the enterocyte cytoplasm causes a _.

1) bundle-forming pilus (BFP), intimin, type 1 pili

2) endotoxin

3) poorly invasive

i) diarrhea

ii) attaching and effacing (A/E) lesions

iii) bundle-forming pilus (bfp)

iv) effectors
TIR, the intimin receptor
intimin

v) enterocytes

vi) watery diarrhea

21

Escherichia coli:
Intestinal Diseases:
Enteroaggregative E. coli (EAEC):

1) Adherence

2) Toxins

3) Invasion

i) May cause _ diarrhea in HIV+ individuals in developing countries, _ diarrhea (in USA) and _ diarrhea

ii) Adhere to _ as aggregates composed of many EAEC cells.

iii) Increase _ production, resulting in trapping of these bacteria in a _.

iv) Make _

v) Cause a _ and subtle _ (but no fecal leucocytes). _ may occur.

1) mucus-associated autoagglutinin, type 1 pili

2) endotoxin, enteroaggretative ST-like toxin (EAST)

3) none

i) chronic
infant
acute traveler's

ii) enterocytes

iii) mucus
biofilm

iv) EAST

v) watery discharge
inflammation
Low-grade fever

22

Escherichia coli:
Intestinal Diseases:
Enteroinvasive E. coli (EIEC):

1) Adherence

2) Toxins

3) Invasion

i) Resemble _ in their pathogenic mechanisms and the clinical illnesses they cause.

ii) Cause disease by invading _, lysing _ vesicles and escaping into the _, where these bacteria multiply and cause cell destruction.

iii) Lack known (common / specific) pili, but do have (common / specific) pili, and (fimbrial / afimbrial) adhesions.

iv) Have a type _ secretion system.

v) Not known to produce _.

vi) Clinical presentation is a _, sometimes with _ and _.

1) type 1 pili, afimbrial adhesins

2) endotoxin

3) very invasive (type III secretion system)

i) Shigella spp.

ii) enterocytes
endocytic
cytoplasm

iii) specific
common
afimbrial

iv) III

v) enterotoxins

vi) watery diarrhea
blood
fecal leucocytes

23

Escherichia coli:
Intestinal Diseases:
Enterohemorrhagic E. coli (EHEC):

1) Adherence

2) Toxins

3) Invasion

i) Often are O(#):H(#), but increasingly can be other serotypes.

ii) Most often cause _, which is characterized by bloody stool and little or no fever. About 73,000 cases/year in USA.

iii) In children, this infection can also result in _, a condition referred to as _. Antibiotics can increase risk of HUS.

iv) EHEC is considered an _ pathogen, as these bacteria were only first described in 1983 and cases/year are still increasing.

v) Usually transmitted to people via _, classically (but not exclusively) _. 1993 outbreak in Washington state sickened 732 people, with 195 hospitalizations and 4 deaths.

vi) Can also be transmitted via _ or other handling of infected _.

vii) Incubation period is usually _-_ days. Initially see _ and _ (in 50% of infections). 1-2 days later, the diarrhea becomes _ and _ occurs. This usually lasts for ~10 days.

viii) In ~5-10% of those infected (mostly children, occasionally the elderly) the disease progresses to _.

ix) Pathogenesis involves close adherence via _, followed by production of _ which causes _ damage (?) and can be absorbed into the circulation where it can affect the kidneys.

1) type 1 pili, intimin

2) shiga toxin, endotoxin

3) poorly invasive

i) O157:H7

ii) hemorrhagic colitis

iii) acute kidney failure
hemolytic uremic syndrome (HUS)

iv) emerging

v) ingestion of foods
undercooked meat

vi) petting zoos
animals

vii) 2-4
nonbloody diarrhea and vomiting
bloody
abdominal pain

viii) HUS

ix) intimin
Stx
colonic

24

Escherichia coli:
Urinary tract infections (UTIs):

Uropathogenic E. coli cause ~80% of _-acquired _ UTIs but only ~20% of _ UTIs (this group can also have bacterial colonization of catheters without infection).

E. coli UTIs include both _ (_ infection) and _ (_ infections). _ is very common and recurs in ~20% of patients.

Highest risk group is _ (fecal E. coli from the intestines contaminate the perineal and urethral areas; mechanical effect of sexual intercourse then provides those E. coli access to the bladder).

community-acquired bacterial
nosocomial

cystitis (bladder)
pyelonephritis (kidney)
Cystitis

sexually-active women

25

Escherichia coli:
Urinary tract infections (UTIs):
Virulence factors:

i) Type _/common _ (_ binding).

ii) _: associated with pyelonephritis. Named for their ability to bind to the _ blood group antigen, which is also present on the kidney epithelium. This _ disaccharide is also known as the _ antigen.

iii) _ (sometimes)

iv) _

v) can be _

i) 1
pili
mannose

ii) P-pili (Pap pili)
P
D-gal-D-gal
Forssman

iii) Hemolysin

iv) Endotoxin

v) invasive

26

Escherichia coli:
Meningitis:

E. coli is one of the two leading causes of _ meningitis (the other is _).

75% of E. coli neonatal meningitis is caused by strains possessing the _ antigen.

K1 antigen is a homopolymer of _. It inhibits _ and _. It also resembles the host (_).

_ is probably important for inducing symptoms (fever, shock, etc.) of E. coli neonatal meningitis.

neonatal
Group B strep

K1

sialic acid
phagocytosis
complement activation
molecular mimicry

Endotoxin

27

Escherichia coli:
Diagnosis:

E. coli can be easily grown on _ agar, where it forms (white / pink) colonies due to (lactose / lack of lactose) utilization (distinguishing it from _ and _, which (use / do not use) lactose and form (white / pink) colonies).

E. coli can be further identified by biochemical tests included in _ testing panels such as _.

Differentiation between _, _, etc. can be made on the basis of serotyping, clinical grounds, and molecular testing (e.g. for the presence of the LT genes).

MacConkey
pink
lactose
Salmonella and Shigella
do not use
white

enteric
API strips

EHEC, ETEC

28

Escherichia coli:
Prevention and Treatment:

Sanitary and hygienic behavior reduces E. coli _ infections and _.

Treatment varies with disease condition, ranging from _ (for most ETEC cases) to use of _ (for neonatal meningitis and UTIs).

For HUS caused by EHEC, _ and _ are used. Antibiotics are _. 3-5% death rate even with proper therapy.

enteric
UTIs

symptomatic
antibiotics

kidney dialysis
blood transfusion
contraindicated

29

Helicobacter pylori:
Biologic characteristics:

H. pylori was discovered in 1982 and initially classified as a _ species.

It is a curved, Gram-(positive / negative) _ that is (motile / non-motile) and _ (unlike C. jejuni, it grows better at (37 / 42) °C than (37 / 42) °C).

Urease-(positive / negative)

Campylobacter

negative
rod
motile
microaerophilic
37
42

positive

30

Helicobacter pylori:
Reservoirs and Transmission:

H. pylori has a _ reservoir (other Helicobacter spp. infect other _).

transmitted between people via _ or _ routes.

More people are colonized in developing countries than in USA.

i) by age 10, >70% of children in developing countries are colonized vs. only 30% of total US population.

ii) colonization related to _ size and _ status.

iii) colonization increases with _; by age 60, >50% in US are colonized.

iv) colonization rate in US seems to be (increasing / decreasing) recently.

human
animals

fecal-oral
oral-oral

ii) family
colonization

iii) age

iv) decreasing

31

Helicobacter pylori:
Virulence Factors:

Virulence factors for colonization: the stomach was once thought to be _ because of its extremely low pH.

i) Produces _, which (raises / lowers) local pH surrounding the H. pylori cell.

ii) Uses _ to move into mucus layer, where pH is much (higher / lower).

Virulence factors for Disease:

i) Produce _ which can damage stomach epithelial cells.

ii) Nearly all strains causing ulcers carry the _, which encodes a type _ secretion system and _ (an effector that helps induce inflammation).

iii) make _, which can also help induce inflammation

iv) chronic _ / _ may increase nutrient availability for H. pylori.

sterile

i) urease
raises

ii) flagella
higher

i) VacA (vacuolating cytotoxin)

ii) cag pathogenicity island
IV
CagA

iii) LPS

iv) inflammation / urease

32

Helicobacter pylori:
Pathogenesis and Disease:

most colonized people develop an initial mild _ disease (_, _, etc.)

most colonized people then develop a mild _ in the stomach that may persist; this is referred to as chronic _.

most colonized people never develop any serious illness but >1% of colonized per year develop either _ or _. Probably due to inflammation resulting from: _ (from urease), _, and _ (endotoxin of H. pylori relatively weak).

i) nearly all (gastric / duodenal) ulcers are associated with H. pylori colonization.

ii) ~70% of (gastric / duodenal) ulcers are associated with H. pylori colonization (most of the rest are associated with use of _ such as aspirin).

iii) a small percent of colonized people in the US develop _ or _; the percent of colonized people developing these diseases is higher elsewhere (perhaps because people there are colonized younger).

GI disease (vomiting, nausea, etc.)

inflammation
gastritis

duodenal or gastric ulcers
ammonia
VacA
CagA

i) duodenal

ii) gastric
nonsteroidal anti-inflammatory drugs [NSAIDs]

iii) gastric cancer
gastric lymphoma

33

Helicobacter pylori:
Diagnosis:

_ via endoscopy: expensive and invasive, but can exclude malignancy

i) biopsied material can be _, _, or tested for _ to detect the presence of H. pylori.

ii) this material can also be examined for pathology.

_ tests: noninvasive and cheaper but can involve radioisotopes or expensive equipment.

i) can use 14C radioactive _ or 13C-labelled _.

_ tests also available.

biopsy

Gram-stained
cultured
urease

breath

i) urea
urea

serologic

34

Helicobacter pylori:
Treatment:

Combination therapy is typically used, often including >1 antimicrobial (e.g., _ and _) and an acid blocker (e.g., _). This approach eradicates H. pylori from the stomachs of -90% of treated patients

clarithromycin and bismuth salts
omeprazole

35

Escherichia coli:
Biology:

a. Recall that:

i) O antigen is the (short / long) _ chain extending outwards from _.

ii) H antigen (if present) is a _ antigen.

iii) K antigen (if present) is a _ (_) antigen.

b. There are >160 recognized O types and 55 recognized H types of E. coli which, in combination, allow over 8000 possible O:H serotypes. Convention dictates that E. coli isolates are designated "E. coli", followed by the number designation for their _ antigens, e.g., E. coli O157:H7.

c. Some E. coli serotypes are strongly associated with certain _

i) long
carbohydrate
LPS

ii) flagellar

iii) capsular (surface)

b. O:H:K

c. diseases