Bacteriology of the Colon Flashcards

(85 cards)

1
Q

Gut bacteria that can cause systemic disease

A

Listeria

Salmonella Typhi/non typhoidal salmonella serotypes

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2
Q

Pathogens that invade cells/ cause inflammation/intoxicate

A

Shigella
Enterohemorrhagic E. Coli
Campylobacter/Helicobacter

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3
Q

Bacteria whose pathology and symptoms are due to exotoxin production

A

Vibrio Cholerae

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4
Q

What are the sites of terminal digestion and absorption of nutrients

A

The mucosal villi and crypts lined by a single layer of columnar epithelial cells

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5
Q

What absorbs most of the water from chyme

A

The large intestine (90%)

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6
Q

Differences in absorption between small and large intestine

A

In large intestine, villi are absent, and the colonic mucosa is full of Crypts of Lieberkhun

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7
Q

Fluid Balance
How many Liters of fluid enter the upper gastrointestinal tract each day?
What is the the average daily fecal excretion?

A

8.5 L

150mL

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8
Q

Infections alter normal intestinal physiology in one of three ways:

A
  • Penetration through an intact mucosa
  • Inflammatory or cytotoxic destruction of the ileal or colonic mucosa
  • Shift in bidirectional water and electrolyte fluxes in the upper small bowel by intraluminal toxins or minimally invasive organisms
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9
Q

Barriers to invading pathogens (6)

A
  1. Epithelial barrier and intestinal motility (epithelium continuously regenerating)
  2. Structural barrier (Tight cell junctions)
  3. Chemical barrier (Gastric acidity)
  4. Paneth cells (Secrete antimicrobial peptides)
  5. Adaptive immunity (Mucosal associated lymphatic tissue)
  6. Microbial recognition (Pattern Recognition Receptors)
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10
Q

5 Take home points about normal microbiota

A
  • Neonates are colonized following delivery
  • Colonization drives the maturation of the mucosal immune system
  • Intact microbiota monopolizes physical and nutritional niches at the mucosal surface
  • Normal microbiota contributes to nutrient acquisition by fermenting non-digestible dietary components, contributing to normal growth and differentiation
  • Normal microbiota provide powerful host defense mechanism to limit the ability of pathogens to take up residence and invade the human body
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11
Q

Listeriosis

A

Aerobic non spore forming Gram positive rod

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12
Q

Listeriosis
Human Pathogen:
Growth range:
How it enters the body:

A

Human Pathogen: L. monocytogenes
Growth range: 1-45° and high salt concentrations
How it enters the body: Penetration through an intact mucosa to the reticuloendothelial system

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13
Q

Listeriosis is restricted to well defined populations:

A
  1. Neonates
  2. Elderly
  3. Pregnant Women
  4. Persons with defects in cellular immunity
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14
Q

Listeria pathogenesis

A
  1. Ingest contaminated food
  2. L. monocytogenes are able to survive in stomach acid and bile salts
  3. Adherence to host cells
  4. Entry into enterocytes or M cells in Peyer patches
  5. Phagosome is initially intact
  6. pH drop in the phagosome activates listeriolysin O and 2 different phospholipase C enzymes
  7. Bacteria replicate free in cytoplasm
  8. ActA located on one pole of the bacterium polymerizes host actin allowing intracellular movement to membrane
  9. Actin polymerization pushes the bacterium to uninfected cells and the cycle begins again
  10. Systemic infection - passage through the intestinal lining, entry into macrophage and spread
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15
Q

Listeria - Epidemiology

A

Human listeriosis is sporadic
Undercooked processed meats, unpasteurized milk, contaminated cheese…
Can be isolated from the feces of animals
Can grow inside of wide range of temperatures

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16
Q

Human to human transmission of Listeria occurs from _____ to ____ in _____

A

mother; child; utero

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17
Q

Lysteria Clinical Diseases
Neonatal:
Pregnant Women:
Adults:

A
  • Neonatal disease
    Early onset disease acquired in utero - abortion, stillborn or premature birth
    Granulomatosis infantiseptica = granuloma formation in multiple organs
    Late onset disease -2-3 weeks after birth - characterized by meningitis
  • Pregnant women (third trimester - influenza-like)
  • Adults
    Healthy - mild influenza like illness
    Immunocompromised - meningitis
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18
Q

Listeria - Laboratory Diagnosis

A

Gram stain of CSF for meningitis patients
Culture - 1 to 2 days - cold enrichment
Biochemical Tests
Serologic tests - 13 serotypes

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19
Q

Listeria - treatment, prevention, control

A

Ubiquitous in environment so control is difficult
No vaccine
Combination treatment = gentamicin with penicillin
Naturally cephalosporin resistant

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20
Q

Salmonella:

Method of Entry:

A
  • Gram negative rods, found in soil ,water, normal intestinal flora
  • Method of Entry: Penetration through an intact mucosa
  • Inflammatory or cytotoxic destruction of the ileal or colonic mucosa
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21
Q

Serotyping schemes to identify individual salmonella isolates

A

H antigen = flagellar proteins
K or Vi = capsular antigens for E. coli and S. typhi, respectively
O antigens = Lipopolysaccaride

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22
Q

Salmonella does not ferment _________

A

lactose

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23
Q

Salmonella Pathogenesis

A
  • Broad host range EXCEPT for Typhi and Paratyphi
  • Salmonella can resist stomach acid; attach to the mucosa of the small intestine and invade into M cells and enterocytes
  • Replicates within endocytic vacuoles
  • Endocytic vacuoles are modified and stabilized by the injection of bacterial proteins through two type III systems = spacious vacuole
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24
Q

Pathogenicity Island 1 genes = ______

Pathogenicity Island 2 genes = ______

A

invasion; evasion of immune response

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25
Gastroenteritis due to Salmonella
- Infection and replication induces an inflammatory response - Disruption of the enterocytes and malabsorption - Release of prostoglandins, stimulation of CAMP and fluid secretion
26
Pathogenesis of Enteric or Typhoid Fever
- Bacteria invade cells and replicate as in gastroenteritis - Typhi also replicates in macrophages and spreads through the reticuloendotheilal system to liver, spleen, blood and bone marrow - Bacteremia causes the fever and may lead to localized suppurative infections or in rare cases perforation of the intestine
27
Gastroenteritis to salmonella Epidemiology (6)
1. Ingestion 2. Incidence is greatest in children (under 5) and adults (older than 60) 3. Occurs most frequently during the summer months 4. Common food sources include poultry, eggs, dairy products, ground beef 5. Nontyphoidal US infections > 1.4 million with 600 deaths/year 6. Infectious dose is high (10^6 - 10^8 bacteria)
28
Typhoid or Enteric Fever Epidemiology
- Relative to strains causing gastroenteritis, the inoculum for Typhi is low - Transmission person to person and through fecal contamination - Enteric fever is endemic to India, South/Central America, Africa - Travelers should be vaccinated when going to endemic areas
29
Salmonella outbreaks in children can occur with the introduction of _____
PET TURTLES!
30
Salmonella clinical diseases: S. Gastroenteritis: S. Septicemia: Enteric Fever:
- S. Gastroenteritis: Symptoms - 6 - 48 hours after consumption of contaminated food (fever, cramps, headache, nausea, vomiting) - persists for 7 days but self limiting - S. Septicemia: ALL SALMONELLA SPECIES CAN CAUSE A BACTEREMIA - Immunocompromised patients at risk for septicemia - Enteric Fever: 10-14 days after ingestion - gradual fever, headache, myalgias, anorexia, rose spots - After bacteremic phase gastrointestinal symptoms occur: colonization of gall bladder and reinfection of the intestines
31
Mary Mallon - Typhoid Mary
- First person identified in US as asymptomatic carrier of S. Typhi - She was a cook - infected 51 people, three of whom died - Typhoid fever was traced to the places where she worked - Arrested and quarantined She died of pneumonia and complications of a stroke
32
Salmonella - Laboratory Diagnosis
- Stool culture - must use selective medium to recover salmonella versus normal flora - Lactose negative, motile, makes H2S, other differential biochemical tests - Epidemiological investigations use pulsed-field electrophoresis
33
Salmonella - Treatment, Prevention, Control
- Symptomatic relief but no antibiotics for Salmonella gastritis - Careful food preparation and storage, hand washing - Ampicillin, trimethoprim-sulfamethoxazole for systemic infections
34
Traveler vaccinations for Salmonella
Live attenuated vaccine Ty21a: good for 5yrs, 6 capsules every other day, booster at 4 yrs, not recommended for children Typhim - Vi polysaccharide capsular vaccine, not recommended for children under 2 years of age
35
Shigella Characteristics
- Family member of the Enterobacteriaceae (Gram negative) - Non motile (no flagella), does not ferment lactose, no capsule - Infectious dose is low, easily spread person to person by the fecal oral route - 4 recognized biogroups - dysenteriae, flexneri, boydii, sonei
36
Shigella - | 4 recognized biogroups
dysenteriae, flexneri, boydii, sonei
37
Shigella - Pathogenesis
1. Shigella replicate intracellularly in the colon 2. They invade M cells in Peyer patches and initially colonize the small intestine 3. Bacteria inject type III "effectors" into cells to instruct the cytoskeleton to engulf them 4. The effectors are called Invasion Protein Antigens or IpaA, IpaB, IpaC and IpaD 5. Once inside of host cells the bacterium lyses the vacuole and replicates free in the cytoplasm 6. Similar to Listeria, Shigella polymerize host actin to move to the membrane to penetrate uninfected cells 7. Shigella induce apoptosis in phagocytic cells which leads to a release of IL-1β resulting in intense inflammatory response
38
Shigella - Toxins
Ipa proteins - induce bacterial uptake - injected by the type III secretory system Shigella secrete Shiga toxin - Exported by a type II secretory pathway - Shiga toxin is a typical A:5B toxin *B = recognizes the host glycolipid GB3 *A = enzymatic activity of the toxin; cleaves 28S ribosomal RNA disrupts protein synthesis and colonic epithelium dies and cells and mucous are lost from the large intestine
39
____ are the only reservoir for Shigella | ______ is a pediatric disease (60% of cases in children under 10
Humans | Shigellosis
40
Shigella Transmission
Infectious dose is low (100-200 bacteria) so person to person transmission is easy through fecal-oral route
41
Shigella - Clinical Disease
``` Incubation period after ingestion 1-3 days Symptoms - Abdominal cramps - Tenesmus or straining to defecate - Diarrhea - Pus and blood in stools - Neutrophils and mucous in stool ```
42
Dysentery
Term coined by Hippocrates to describe the frequent passage of stool containing blood and mucous
43
Shigella laboratory Diagnosis
- Lactose negative colonies on selective medium (colorless as opposed to pink colonies on MacConkey agar) - Shigella is NOT motile while salmonella is flagellated and motile and Shigella does not produce H2S
44
Shigella - Treatment, Control and Prevention
- Mild infections are usually self limiting - Antibiotic treatment may shorten illness but are only used for severe illness - Antidiarrheal agents such as loperamide or diphenoxylate with atropine can make illness worse - In presence of antidiarrheal agents, Shiga toxin is not flushed from the system, leading to more extensive cell death and inflammation
45
Enterohemorrhagic E. Coli (EHEC) - Characteristics
Family member of the Enterobacteriaceae (Gram Negative) Infectious dose is low (100-200 bacteria) - spread person to person by fecal oral route Member of the family of pathogenic E. coli
46
EHEC pathogenisis
Culture filtrates from these bacteria were cytotoxic to Vero cells Toxic activity could be neutralized with antibodies to Shiga toxin Produce a distinct histopathology called attaching and effacing lesions EPEC = EHEC that do not synthesize Shiga toxins Alterations in the cellular cytoskeleton due to bacterial type III secretion EHEC also injects a protein called Tir Bacteria grow in place and release shiga toxin
47
Tir
EHEC protein that integrates into the mammalian cellular membrane and binds tightly to a bacterial outer membrane protein called intimin
48
Shiga toxins are encoded on lysogenic bacteriophage in E. Coli (2 types)
``` Stx-1 = Shiga toxin Stx-2 = 60% homology to Shiga toxin (A:5B) ```
49
Shiga toxin
Stops host protein synthesis by cleaving host ribosomal RNA Binds to cell with GB3 receptor Strains expressing both toxins are more virulent Stimulate the expression of inflammatory cytokines
50
EHEC epidemiology
EHEC associated with certain H and C serotypes Certain serotypes may be selected for in the intestinal tract of cattle Undercooked beef, meat, cattle feces
51
EHEC clinical diseases Hemorrhagic colitis: Hemolytic uremic syndrome (HUS):
Hemorrhagic colitis: Characterized by severe abdominal pain and bloody diarrhea that occurs 3-4 days after ingestion of contaminated food Hemolytic uremic syndrome (HUS): Occurs in children under 10 years of age - acute renal failure; thrombocytopenia; microangiopathic hemolytic anemia *vomiting in about 50% of patients
52
EHEC laboratory diagnosis
Culture - differential identification based on the inability to ferment sorbitol EHEC is colorless and normal Look for certain serotypes associated with HC or HUS Immunoassays to detect the presence of Stx-1 or Stx-2
53
EHEC treatment, prevention and control
Treatment consists of supportive care Monitoring of the development of microangiopathic complications (HUS) Antiperistaltic agents increase the risk of systemic complications Antibiotic therapy is generally not beneficial - may increase shiga toxin production and release Careful cooking of food
54
Campylobacter: Physiology and Structure
Gram negative curved rod Microaerophilic, can grow at 42° Non-fermentative Motile with single flagellum at one or both poles
55
Major isolates of Campylobacter associated with human disease
C. jejuni C. upsalensis C. coli C. fetus
56
Campylobacter pathogenisis
1. Inflammation - gastrointestinal infections produce histologic damage to the mucosal surfaces of the jejunum, ileum and colon 2. Infection is associated with the development of autoimmune disorders (Guillan-Barre syndrome; reactive arthritis) 3. Other than LPS and antigenic cross-reactivity, one toxin has been discovered that stops cell division - cytolethal distending toxin (cdt)
57
Campylobacter Epidemiology
Infections are associated with the consumption of contaminated food, particularly chicken Not a reportable disease - difficult to grow and identify bacteria
58
Highest isolation rates of Campylobacter are in ______ and ______ _____
Summer and early fall
59
Campylobacter clinical diseases Acute enteritis: Extraintestinal infections:
Acute enteritis: Gastrointestinal infection characterized by bloody stools, inflammation, ulcerated mucosa, diarrhea Extraintestinal infections: C. fetus in compromised patients - resistant to serum antibody and complement killing
60
Campylobacter - laboratory diagnosis
Microscopy - darting motility in fresh fecal samples - S shaped organism in stool - Presence of RBCs and WBCs in stool Antigenic detection Culture - difficult - slow growth; microaerophilic
61
Campylobacter - Treatment, Prevention and Control
Treatment recommendations - Fluid replacement as long as diarrhea lasts Severe cases are treated with azithromycin or erythromycin Severe infections include: high fever; bloody stool; symptoms lasting over 1 week
62
Helicobacter - Physiology and Structure
``` Gram negative curved rods Multiple polar flagella, highly motile Microaerophilic Produce a powerful urease enzyme that converts urea to NH3 and CO2 Difficult to culture and isolate ```
63
Helicobacter - pathogenesis
Gastric colonization can be lifelong so part of the pathogenesis involves survival in this extreme environment 1. Urease expression allows the bacterium to survive in acidic gastric juice 2. They swim through the mucus using flagella 3. They adhere to the gastric epithelium via specific receptors that include the Lewis blood-group Ags and laminin 4. pH at the epithelial surface is 7.0
64
Helicobacter - pathogenesis | The production of ______ ______ in humans in strongly correlated with the possession of ___ genetic loci
Peptic ulcers; two
65
VacA (Helicobacter)
A multifunctional toxin - Forms anion specific channels - forms large vacuoles in cultured cells - alters tight junctions - induces gastric epithelial erosion in animal models
66
Second locus associated with peptic ulcers (Helicobacter)
Second locus encodes many genes including: Specialized secretion system called a type IV secretory system This secretion system injects CagA which induces IL-8 release - also induces pedestal formation Other products also enhance IL-8 transcription in epithelial cells
67
Helicobacter pathogenesis Urease: Flagella: Adhesins:
Urease: secretion to survive in gastric juice Flagella: allows them to propel into mucus layer and to reach the gastric epithelial cells Adhesins: allow bacterium to stick to the apical region of epithelial cell
68
``` Heliobacter - Epidemiology Reservoir: Transmission: Highest Incidence: Asymptomatic: Increased risk: Associated diseases: ```
Reservoir: Humans only Transmission: fecal-oral route Highest Incidence: Developing countries Asymptomatic: 70-80% of infected individuals Increased risk: Persons with gastritis, gastric ulcer or duodenal ulcers Associated diseases: infection is also associated with gastric adenocarcinoma and gastric B-cell lymphomas
69
Helicobacter - Clinical diseases Gastric Helicobacters: Enterohepatic Helicobacters:
Clinical outcome depends on site of colonization Gastric Helicobacters: H. pylori; gastritis, peptic ulcer, gastric adenocarcinoma, gastric mucosa-associated lymphoid tissue (MALT) B-cell lymphomas Enterohepatic Helicobacters: Isolates from homosexual men with procititis, proctocolitis, or enteritis
70
A chronic inflammatory response to Helicobacter may contribute to the development of ______
cancer
71
Helicobacter - Laboratory Diagnosis
1. Urea breathing test 2. Histologic examination of gastric biopsy 3. Biochemical detection of urease activity from gastric biopsy 4. Detection of H. pylori antigens from stool samples
72
Helicobacter - Treatment, Prevention and Control
Recommended treatment: Proton pump inhibitor + macrolide + β-lactam NO vaccine - not sure whether eradication is good
73
Vibrio Structure: Important human pathogens:
Structure: Gram negative curved rods Important human pathogens: - Vibrio cholerae serogroups 01 and 0139 - produce cholera toxin - Vibrio vilnificus - associated with wound infections and septicemia - Vibrio parahaemolyticus - gastroenteritis, wound infection, septicemia
74
Vibrio - Physiology and structure
``` Curved rods with single polar flagella Require NaCl for growth Oxidase positive Toxin co-regulated pili Serogroups are based on LPS ```
75
Vibrio serotypes
Serotypes O1 and O139 produce cholera toxin and are associated with epidemic disease Serotype O1 is subdivided into Classical and El Tor biotypes - Current pandemic is due to El Tor
76
Vibrio pathogenisis (Cholera toxin)
Cholera Toxin is an A:5B protein Cholera toxin and Labile toxin (ETEC) are structurally and functionally similar Toxins bind ganglioside receptors on intestinal epithelial cells = GM1 The A subunit ADP-ribosylates the G protein and induces cAMP production Camp stimulates the CFTR inducing Cl- secretion, inhibiting NaCl absorption and causing water efflux - tremendous loss of water
77
Other factors encoded on Vibrio phage
TCP = Toxin coregulated pilus; used by bactera to adhere to the mucosal epithelium and used by the phage to infect the bacteria Chemotaxis proteins - also used for adherence to host epithelial cells Zona Occludens toxin (ZOT) - disrupts tight junctions Accessory cholera enterotoxin (Ace) - increases fluid secretion
78
Why is Vibrio pathogenesis hard to prevent?
The expression of toxins prevents the development of live attenuated vaccines
79
Vibrio epidemiology
Vibrio grows in nature in estuarine and marine environments Pathogenic vibrios infect shellfish Asymptomatic individuals can shed the organism Cholera is transmitted by contaminated water and food Infectious dose = approximately 10^8 with normal stomach acid levels
80
Vibrio clinical diseases: V. Parahaemolyticus: V. Vulnificus:
2-3 days after ingestion, abrupt onset of watery diarrhea and vomiting DIarrhea becomes colorless and odorless and contains small specks of mucous = rice water stool Dehydration, cramps, metabolic acidosis Mortality rate can be 60% if untreated V. Parahaemolyticus: gastritis ranging from mild to severe V. Vulnificus: wound infection/septicemia
81
Vibrio laboratory diagnosis
Microscopy - curved gram-negative rods in large numbers in stool material from wound infections Culture - Relatively easy to isolate in the laboratory; confirmation by a relatively small number of biochemical tests
82
Vibrio treatment, prevention and control
1. Fluid electrolyte replacement 2. Antibiotics can reduce toxin production and decrease transmission 3. Improvements in sanitation 4. Vaccines - Formalin inactivated whole cell vaccine (IM) - Dukoral given PO - also given for travelers diarrhea due to ETEC
83
Dukoral
Heat and formalin killed O1 classical and El Tor strains - IgA response prevents colonization Non-toxic B subunits - IgA response prevents toxin binding
84
Klebsiella Pneumonia Resistant to Carbapenems (CRKP) and Carbapenem resistant Enterobacteriaceae (CRE)
Cephalosporins and Carbapenems are antibiotics usually reserved to treat the sickest patients Difficult to control, can be fatal in up to 40% of cases
85
Family of Pathogenic E.Coli (5):
1. Enterotoxigenic E. coli (ETEC) - Labile toxin (LT‐1) and stable toxin (STa) 2. Enteropathogenic E. coli (EPEC) - attaching and effacing lesion 3. Enteroinvasive E. coli (EIEC) - like Shigella, invasive, inflammatory 4. Enteroaggregative E. coli (EAEC) - adherence, colonization 5. Uropathogenic E. coli (UPEC) - fimbrial adherence, UTI