Microbiology of the Lower GI - Zimmer Flashcards

1
Q

What are the GI system defenses of the intestines?

A
  • Normal flora
  • Peyer’s Patches
    • M cell: conduit to PP, capable of transporting large antigens
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2
Q

What is the normal flora of the large intestines?

A
  • Microbe rich, “microbiome” studied here
  • Anaerobes
  • Gram-negative rods
  • Enterococcus – can survive wide range of stressors and environmental conditions
  • Spirochetes
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3
Q

What are the first colonizers of breast-fed infants?

A
  • facultative anaerobic bacterial groups such as:
    • streptococci
    • staphylococci
    • enterococci
    • lactobacilli
    • enterobacteria
    • together with some strictly anaerobic ones
      • especially bifidobacteria
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4
Q

What are the first colonizers of formula-fed infants?

A
  • microbiota → more diverse and prone to changes
  • contains higher counts of:
    • Bacteroides
    • Clostridium
    • Enterobacteriaceae
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5
Q

Why is the normal flora of the lower GI tract beneficial?

A
  • Generate vitamins, help in digestion
  • Stimulate the development of immunological tissues
  • Prevent establishment and infection of alien microbes
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6
Q

What are the four mechanisms that microorganisms cause disease?

A
  1. Toxin production – bacteria release toxin that causes illness.
  2. Host immune response – response of host to microbe that causes illness.
  3. Microbial proliferation and invasion – growth and spread of microbes that causes damage that is significant in illness.
  4. Cancer – Microbe promotes uncontrolled proliferation of cells of host organism
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7
Q

When does true “food poisoning” occur?

A
  • True food poisoning occurs after consumption of food containing toxins
    • Symptoms begin almost immediately after ingesting the food with toxin in it
      • 30 min to 6 hr incubation period
    • Toxin is pre-formed
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8
Q

How are food-associated infections different from food poisoning?

A
  • Symptoms begin with a longer incubation period
  • Organisms produce toxin in the GI tract or invade mucosal epithelium
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9
Q

What is a bacterial exotoxin when it targests the intestines?

A

Enterotoxin

(something bacteria excretes)

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10
Q

What three bacteria cause food poisoning by generating pre-formed toxins in food?

A
  1. Staphylococcus aureus
  2. Bacillus cereus
  3. Clostridium botulinum
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11
Q

What are the symptoms when S. aureus causes food poisoning?

A
  • Nausea, vomiting, stomach cramps, and diarrhea for 1-3 days
  • Appear 1-7 hrs following ingestion of food
  • Self-limiting, once toxin is gone, illness is gone
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12
Q

How do you get a positive diagnosis of S. aureus causing food poisoning?

A
  • Toxin-producing S. aureus can be identified in stool or vomit
  • Most conclusive test is the linking of an illness with a specific food, or in cases in which multiple vehicles exist, detection of pre-formed enterotoxin in food sample(s).
    • Only necessary when tracking outbreaks
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13
Q

How does S. aureus cause food poisoning?

A
  • Can generate 7 different toxins
  • Ingestion of toxin, not the bacterium, is what causes the illness
  • Toxin can survive high temperatures, although S. aureus cannot.
    • However it is one of the most resistant non-spore forming human pathogens, survives in dry state for extended periods.
  • S. aureus temperature range of 15°-45°C and NaCl concentrations as high as 15 percent for growth
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14
Q

Is antibiotic treatment a good option for S. aureus food poisoning?

A

No, antibiotics don’t target the toxin.

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15
Q

Bacillus cereus

Gm +/-

Spore forming?

Aerobe/Anaerobe

Hemolysis?

A
  • Gram +
  • Large Bacilli
  • endospore-forming
  • Facultative anaerobe
  • Mostly motile
  • Β hemolytic
  • Box-car shaped gram positive rods
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16
Q

What is the Bacillus cereus reservoir?

A

Spores can survive rice cooking process

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17
Q

Where are Bacillus cereus spores commonly found?

A

B. Cereus spores are commonly found in the soil and sometimes in plant foods that are grown close to the ground – such legumes, cereals, spices etc..

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18
Q

What are the two forms of Bacillus cereus Food Poisoning?

A
  • Emetic (vomiting):
    • 1 to 6 hours incubation
    • Nausea and vomiting
    • resembles the vomiting illness caused by Staphylococcus aureus enterotoxins
  • Diarrheal:
    • 6-15 hours incubation
    • Watery diarrhea and abdominal cramps
    • clinically similar to the symptoms of Clostridium perfringens infection
  • Duration for both only about 24 hrs
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19
Q

What is the mechanism of Bacillus cereus Food Poisoning Emetic (vomiting) type?

A
  • Mechanism:
    • Caused by preformed enterotoxin that forms holes in membranes:
      • Cereulide = an ionophoric low molecular-weight peptide that is pH-stable and heat- and protease- resistant
    • Self limiting
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20
Q

What is the mechanism of Bacillus cereus Food Poisoning Diarrheal type?

A
  • Mechanism:
    • Caused by large molecular weight enterotoxin that causes intestinal fluid secretion, probably by several mechanisms
    • This toxin is not likely pre-formed!
  • Ingestion of large amounts of bacteria cause it to generate the toxin in the small intestine
  • Vulnerable populations might get sicker and require antibiotics
  • Poor outcomes for systemic infection
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21
Q

How do you positively diagnose Bacillus cereus?

A
  • Because of its ubiquity, B. cereus often is ignored or dismissed as a contaminant when found in a culture specimen.
  • B. cereus in food and vomitus or feces of same serotype
  • Large numbers of B. cereus of serotype known to produce endotoxin
  • Only necessary when tracking outbreaks
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22
Q

Clostridium botulinum

Gm +/-

Shape

Aerobe/Anaerobe

A
  • Gram +
  • Bacilli (Rods with terminal spores)
  • Spore-forming
  • Obligate anaerobe
  • Motile
  • Clostridium
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23
Q

What are the three illnesses associated with C. botulinum?

A
  • Foodborne botulism
    • ingesting toxin in food
  • Wound botulism
    • generating toxic in wound
  • Infant botulism
    • ingesting spores

Not really a GI illness, diarrhea not prominent

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24
Q

How do you diagnose C. botulinum infection?

A
  • Symptoms and history, results of physical exam indicate botulism
  • Tests to exclude other causes of the illness
  • Organism or toxin in stool sample only indirect evidence
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25
What is the treatment for foodbourne C. botulinum infection?
* Ventilator if respiratory failure and paralysis * Antitoxin if paralysis is not yet complete * Remove contaminated food if still likely in gut
26
What kind of toxin does C. botulinum produce?
* **Neurotoxin** * irreversibly blocks the release of acetylcholine from the motoric end plate which results in muscle weakness and paralysis
27
What are the symptoms of Botulism?
* Toxin is absorbed from GI tract to bloodstream * Symptoms * Toxin already produced, symptoms can begin when toxin hits GI tract * double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness
28
What are the symptoms of infant botulism?
* Incubation period, spores have to produce toxin-forming bacteria * Sx: * lethargic, feed poorly, are constipated, and have a weak cry and poor muscle tone * Can lead to paralysis of respiratory system and other muscles
29
What foods reservoirs contain C. botulinum?
* Canned foods that have not been properly heat treated * Honey
30
What are the five bacterias that cause food borne bacterial illness?
1. *Clostridium perfringens* 2. *Salmonella enterica ssp.* 3. *Campylobacter jejuni* 4. *Listeria monocytogenes* 5. *Vibrio parahaemolyticus*
31
What are the mechanisms that food borne illness pathogens cause disease?
* Toxin production – bacteria release toxin that causes illness. * Secretion of exotoxin * Host immune response – response of host to microbe that causes illness. * Microbial proliferation and invasion – growth and spread of microbes that causes damage that is significant in illness. * Direct cellular invasion * Sometimes replicate in cells, sometimes not
32
What are the big 3 (for the US) Bacterial sources of food borne illness?
* Campylobacter jejuni * Intestinal cell invasion * Salmonella enterica * Intestinal cell invasion * Clostridium perfringens * Enterotoxin
33
Clostridium perfringens Gm +/- Shape Aerobe/Anaerobe Motility Toxin
* Gram + * Bacilli * Spore-forming * Obligate anaerobe * Non-motile * Enterotoxin binds to receptors in endothelial cell junctions, then generates pores in host mucosa cells.
34
What are the symptoms of Clostridium perfringens Food Associated Illness?
* Diarrhea and abdominal cramps * Incubation 6 to 24 hours (typically 8-12) * Symptoms last for less than 24 hours * Usually NO fever or vomiting * The illness is not passed from one person to another
35
How do you positively diagnose Clostridium perfringens Food Associated Illness?
* Detection of toxin or high amounts of bacteria in feces * C. perfringens normally present in the GI tract, the problem is when you ingest a C. perfringens load high enough to produce enough toxin to generate symptoms * Commonly acquired in CAFETERIAS * often occurs when foods are prepared in large quantities and kept warm for a long time before serving
36
Campylobacter jejuni Gm +/- Shape Aerobe/Anaerobe Motility
* Gram - * Bacilli (Spirilli) * microaerophilic * Motile * Cold sensitive * Sensitive, sometimes killed before it can be cultured!
37
What agar is used to grow Campylobacter jejuni?
* Karmali agar is a selective medium: * Charcoal-based. * Because it is difficult to grow → must eliminate competing microorganisms * Contains vancomycin active against the gram-positive organisms, cefoperazone active against many normal flora, cycloheximide active against yeasts
38
What are the symptoms in Campylobacteriosis caused by Campylobacter jejuni?
* Diarrhea, cramping, abdominal pain, and fever * 2-5 day incubation * Symptoms can last a week * Can have vomiting * Diarrhea can be bloody!
39
What is the mechanism of Campylobacter jejuni causing Campylobacteriosis?
Symptoms are an inflammatory response to cell invasion
40
How do you positively diagnose Campylobacteriosis?
stool culture
41
What is a possible complication of Campylobacteriosis?
Guillain-Barré syndrome
42
Salmonella Gm +/- Shape Spore formation Motility
* Gram - * Bacilli * Non spore forming * H2S positive * Lactose negative * Motile, flagellated
43
What are the subspecies of Salmonella that cause food borne illnesses/gastroenteritis?
* S. Enteritidis * S. Typhimurium
44
What agar is used to identify Salmonella?
* Salmonella Shigella (SS) agar: * has bile salts that inhibit gram-positive and coliform organisms * contains indicator * lactose fermenting organisms would appear red from the acid produced * Ferric citrate added for indication of H2S production * black color is the produced iron sulfide precipitate
45
What are the symptoms of Salmonellosis?
* Symptoms caused by invasion mechanism! * replicates in host cells as well as invades * Diarrhea, fever, and abdominal cramps * 12 hr to 3 day incubation * Symptoms typically last 4 to 7 days * Most persons recover without treatment * Remember: reactive arthritis as a possible complication
46
What are the food reservoirs for Salmonella?
* Eggs * Dairy * Ice cream * Human transmission
47
How is Salmonellosis positively diagnosed?
Stool culture
48
What is the treatment for Salmonellosis?
Hydration. Antibiotics only necessary if infection spreads beyond gut.
49
Vibrio spp. Gm +/- Shape Aerobe/Anaerobe Motility
* Gram (-) * Vibrio (curved rod) * facultative anaerobes * Flagellated, motile * Oxidase + * Gram-negative rod with single flagellum, water loving
50
What type of culture is used to diagnose Vibrio spp.?
* Mixed culture of oxidase-negative Escherichia coli (colorless) and oxidase-positive Vibrio cholerae (purple) showing how the direct oxidase test differentiates between the two organisms. * Kovács oxidase reagent was added directly to the plate.
51
What are the symptoms of Vibrio parahaemolyticus infection?
* Fairly mild bloody diarrhea, stomach cramps, fever, nausea, and/or vomiting, * Symptoms last less than a week. * In the immunocompromised, it can spread to the blood and cause serious or deadly infections in other parts of the body
52
How is Vibrio infection diagnosed?
Vibrio may be isolated from cultures of stool, wound, or blood.
53
What is the disease causing mechanism in Vibrio parahaemolyticus infection?
* Likely through enterotoxins: * hemolysins TDH (thermostable direct hemolysin) and/or TRH * V. parahaemolyticus lacking these toxins is not pathogenic * Form pores in red blood cells but also in epithelial cells, disrupting gut homeostasis
54
What is the food reservoir of Vibrio parahaemolyticus?
Shellfish
55
Listeria monocytogenes Gm +/- Shape Aerobe/Anaerobe Motility Hemolysis Oxidase +/-
* Gram positive rod-shaped bacteria * Gram (+) * Bacillus * Non-fastidious!!! * able to grow without special nutrition/agar * Flagellated, motile * Non spore forming * Oxidase - * β-hemolytic but zone of discoloration is really only directly under the colonies
56
What are the symptoms of Listeriosis?
* Mild GI infection for most * Fever and muscle aches or stiff neck * More vulnerable are older adults, pregnant women, newborns, and adults with weakened immune systems OPPORTUNISTIC * If you develop while pregnant: fever and chills * Meningitis and sepsis in vulnerable populations
57
How do you diagnose Listeriosis?
* Stool sample ID inappropriate * Positive ID is the bacterium found in a normally sterile site
58
What is the disease causing mechanism of Listeria monocytogenes?
* Invasive mechanism * If you have the classic clinical symptoms, the disease has already reached the invasive stage * Immune cells spread Listeria to other organs * Trojan horse * Liver is a major target
59
What are the food reservoirs for Listeria monocytogenes?
* Foods you don’t cook: * sprouts * deli meats * smoked seafood * soft cheeses * raw milk * Hardy bacterium can hang a long time at food processing facilities
60
How do Shigella spp. cause infection?
* Very closely related to E. coli. * Invasive and produces a toxin * **Transmission**: Mostly bacterium passing from stools or soiled fingers of one person to the mouth of another person.
61
What are the symptoms of infection with Shigella sonnei?
* diarrhea (often bloody) * fever * stomach cramps * Symptoms start 1-2 days following exposure * Usually resolves in 5 to 7 days
62
What are the three types of Shigella species that can cause GI illnesses and diarrhea?
1. Shigella sonnei: most Shigella-caused GI illnesses 2. Shigella flexnori: causes bacillary dysentery 3. Shigella dysenteriae: rarest but most severe dysentery
63
What is dysentery?
* Frequent, small bowel movements with blood and mucus, accompanied by rectal pain and spasms (tenesmus) * Not a synonym for bad diarrhea!
64
What is the difference between Amoebic and Bacillary Dysentery?
* Bacillary → GI illness caused by bacteria * sudden onset fever, chills, pus-containing diarrhea * more prostration (exhaustion) * acute course * Amoebic → GI illness caused by amoeba/protozoa * gradual onset of bloody diarrhea * less prostration (exhaustion) * chronic course
65
Shigella spp. Gm +/- Shape Aerobe/Anaerobe Motility
* Gram (-) * Bacillus * Facultative anaerobe * Nonmotile * Non spore forming * Mainly lactose negative, H2S (-) * “Shigella have no flagella”
66
What is the mechanism of disease Shigella spp.?
* Bacteria gain entry to M-cells in gut * entry mediated by type III secretory system and other effector proteins, and cytoskeletal rearrangements * Macrophages phagocytose bacteria * Macrophage apoptosis occurs * Bacteria survive * Infection of neighboring cell * Shigella actin rockets to move around * Initiation of inflamation
67
What is the treatment for infections caused by Shigella spp.?
* Since Shigella is invasive, if not treated it can spread beyond the GI tract and cause complications * Antibiotics for more severe cases, most usually resolve without antibiotics
68
What is a potential complication of Shigella spp.?
* Possible complication: hemolytic uremic syndrome (HUS) * S. flexnori also a cause of reactive arthritis
69
What is so scary about Shigella dysenteriae?
* **Invasive**, plus has a phage-borne toxin * **Shiga toxin**, also called the **verotoxin** * Toxin acts on vascular endothelial cells * inactivates ribosome =\> dead cell * Most severe dysentery!
70
What are the diseases caused by E.coli?
* **D**iarrhea * **U**rinary tract infection * **N**eonatal sepsis * **G**ram-negative sepsis
71
What makes E.coli pathogenic?
* They acquire a toxin! * **Shiga toxin**-producing E. coli (STEC)—Also known as VTEC or enterohemorrhagic E. coli (EHEC) * *Outbreaks in U.S. O157:H7* * Enterotoxigenic E. coli (ETEC) * Traveler’s Diarrhea, diarrhea in children
72
What is the difference between toxin delivery in ETEC and STEC E.coli strains?
* ETEC * delivery of enterotoxin from lumen * STEC * intimate attachment of bacteria * actin condensation * microvillous effacement * delivery of shiga toxin
73
What are the symptoms of E.coli ETEC and STEC strains?
* Profuse watery diarrhea and abdominal cramping * Can progress to bloody diarrhea for STEC * Fever, chills, nausea with or without vomiting, loss of appetite * Less common: headache, muscle aches and bloating * Incubation → 1-3 days ETEC, 3-8 for STEC * Illness typically lasts 3-4 days, less than 10.
74
What is a potential complication of E.coli STEC strain infections?
STEC: hemorrhagic colitis (HC) and/or HUS can result as a complication; children more vulnerable
75
What is the treatment for E.coli ETEC and STEC strains?
Treatment: antibiotics generally not recommended
76
Why is it generally not recommended to treat infections caused by E. Ecoli TEC and STEC strains?
Antibiotics → kill bacteria Decaying bacteria release **more** toxin
77
What are the food reservoirs for E.coli STEC and ETEC strains?
* STEC =\> gut of cattle * BEEF * Unwashed fruits or vegetables
78
What are E. coli STEC AB5 toxins?
* Each toxin’s genetic locus must have two open reading frames, encoding an A and B component, encoded on the Open Reading Frame * Genes are stxA. stxB on a lambda bacteriaphage * The E. coli toxins themselves are called Stx1 and Stx2. * Stx1 differs from Shigella dysenteriae verotoxin by a single amino acid * Both can be expressed by a single strain of E. coli
79
What is the proposed model for pathological coagulation response leading to HUS in E.coli STEC strains?
* **Shiga toxin injures endothelial cells** during the first few days of infection * possibly even before bloody diarrhoea occurs * **Endothelial injury generates thrombin** * **Fibrin is deposited** in the microvasculature * Concentrations of PAI-1 rise. * PAI-1 **blocks fibrinolysis**, further accelerating the accumulation of fibrin in vessels, and exacerbating the thrombotic injury.
80
What does the future detection of E.coli STEC strains involve?
* Rapid whole-genome sequencing for near-real-time analysis of an emerging pathogenic E. coli strain * Next-gen sequencing: strains completely sequenced within 1 week of receipt (in 2011)
81
What are the supportive care treatments that are upcoming in the future treatment of E.coli STEC strains?
* Renal function protection: * intravenous volume expansion * Monitor for the development of microangiopathic complications * Anti-Stx antibodies and Mn2+ possibly combined with antibiotics less likely to induce toxin production in in vitro and animal models * not available yet * NO antiperistaltic agents! (Increased risk of HUS)
82
What is the primary reservoir for Vibrio cholerae?
Water
83
What is the mechanism of Vibrio cholerae infections causing cholera?
* Typically only serogroups O1 and O139 produce cholera toxin and thus cause cholera * Activates adenylate cyclase * cAMP → decrease Na+ absorption, ­increase Cl- excretion * Water moves into lumen
84
What are the symptoms of cholera?
* An acute illness: * profuse watery diarrhea, sometimes described as “rice-water stools” * vomiting * rapid heart rate * loss of skin elasticity * dry mucous membranes * low blood pressure * thirst * muscle cramps * restlessness or irritability
85
How is cholera diagnosed?
* Confirmed only by isolation of the causative organism from the diarrheic stools of infected people. * Less reliable methods are available for poor areas where laboratories may not be available.
86
What is the treatment for cholera?
* Antibiotic therapy may help for severe cases * Rehydration therapy is really the biggest factor in treatment
87
What is the source of S. Typhi?
Untreated water is the source. | (Humans are the only carriers)
88
What is Typhoid fever? Sx?
* Infection caused by S. Typhi * Life-threatening illness * In GI tract and then to bloodstream * Sx: * High fevers (103-104 °F) * Weakness and headache * Stomach pains, loss of appetite, diarrhea or constipation * Sometimes, a rash of flat, rose-colored spots * After symptoms clear, person could become a carrier * Antibiotic treatment is recommended
89
What are low inoculum organisms?
* Tens to hundreds of virions/cysts/bacteria will cause disease * Examples: Shigella, Giardia, Entamoeba, Norovirus * STEC E. coli, only 100 organisms
90
What are high inoculum organisms?
* Tens of thousands or more needed * Examples: Vibrio cholerae, C. perfringens
91
How are low incoculum organisms acquired?
* Medium of infection does not need to be grossly infected, transmission through bodily contact or almost-clean water possible * Secondary cases common. * Can be spread in cay-care centers, families * Example: Toddler contracts Cryptosporidosis in wading pool
92
How are high incoculum organisms acquired?
* Medium of infection is highly contaminated: * food that is contaminated then held at permissive temps * grossly contaminated water * Secondary cases rare * Example: traveler gets cholera from seafood carried to U.S. from Ecuador in luggage
93
Clostridium difficile Gm +/- Shape? Spore? Motility? Toxins?
* Gram + * Gram positive but sometimes staining is “gram variable” * Bacilli * Spore-forming * Obligate anaerobe * Motile * Makes exotoxins
94
What damage is caused in Clostridium difficile Antibiotic Associated Diarrhea?
* Exotoxins cause cell death, shallow ulcers, pseudomembranes * Early lesions superficial * May eventually invade * Pseudomembranous colitis
95
How do you diagnose Clostridium difficile Antibiotic Associated Diarrhea?
* Stool smear * Difficult to culture * Obligate anaerobe * Toxin detection (2 tests available) * Scope dangerous
96
What is the treatment for Clostridium difficile Antibiotic Associated Diarrhea?
* Antibiotics (metronidazole, vancomycin) * Severe disease: bowel resection * New therapy: fecal transplant