M25: Colonization Flashcards
Pathogen Colonization:
- 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).
- exogenous
a. Adherence, adhesins
b. Multiplication, multiplies - virulence, virulence
- nutrients and/or host factors
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
Bacterial Adherence:
Mediated by both _ and _ interactions
specific
nonspecific
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
Bacterial Multiplication:
- Important for pathogenesis since it increases the delivery of _ (e.g. _) contributing to _.
- Contributes to _ / _ in vivo.
- Requires physiologic _ by the pathogen.
- soluble virulence factors (e.g., toxins)
virulence - survival / persistence
- adaptations
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
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
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)
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
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
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
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
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
Escherichia coli:
Biology:
Like many Enterobacteriaceae, E. coli isolates are commonly differentiated on the basis of their _, _, and _ antigens.
O, H, and K
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
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
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
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)
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
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
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
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
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
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
