gi tract infections quiz - microbio (cls 532)

upper GI tract organs vs lower GI tract

upper GI:

• Mouth ; esophagus ; stomach

lower GI:

• Duodenum/jejunum

• Small intestine—most of infections are happening in bottom of pili (regenerating all the time)

• Ileum ; Colon

normal flora of upper GI tract

• Upper GI tract is sterile

• Acid kills most organisms w/in 30 minutes

food poisoning (general)

• Organism forms toxins while growing in food

• Toxins and bacteria are ingested with food

• Toxins are absorbed by the body and cause disease

• Bacteria are generally shed from the body without colonization

• Most common agents

  • Staphylococcus aureus

  • Bacillus cereus

  • Clostridium botulinum

what is food poisoning classified as?

INTOXICATIONS

staph aueus food poisoning

• Most common intoxication in the US

  • Not sure for other countries due to sanitation & dietary practices

• Heat stable enterotoxin

  • Found in warm foods--processed meats and dairy products

• Food becomes contaminated from exposure to skin and nasal secretions of food handlers

symptoms of s aureus food poisoning

• Explosive onset of symptoms 1-6 hours after ingestion

  • Vomiting

  • Nausea

  • Abdominal cramps

  • Often followed by diarrhea

• Lasts 8-10 hours

• Recovery is usually complete in 24-48 hours

(s aureus food poisoning) staphylococcal enterotoxins

• are superantigens!!!

• Several different serotypes have been identified: SE A, B, C (1,2, & 3), D, E, etc

• Heat stable toxin still present in food after thorough cooking

• One strain can produce more than one type of toxin

• Mode of action

  • Superantigens cause the release of cytokines (IL-2) which induce the symptoms of food poisoning

  • Thought to stimulate the nerve ending in the stomach lining (vagus nerve)

incubation period for s aureus food poisoning

30 min - 8 hours; usually 2-4 hours

bacillus cereus food poisoning type I

• aka diarrheal type

• characterized by abdominal pain with profuse watery diarrhea, nausea, tenesmus, lower abdominal cramps

• 8-16 hours after ingestion of contaminated food

  • meats, vegetable dishes, cakes, sauces, dairy products

• Symptoms abate 12-36 hours later

toxins associated with b cereus food poisoning type I

• 4 heat labile toxins associated with this type

  • Hemolysin BL

    • Dermonecrotic & increases vascular permeability

  • Non-hemolytic enterotoxin

  • Enterotoxin T

  • Cytotoxin K

b cereus food poisoning type II

• aka emetic type

• Characterized by nausea and vomiting 1-6 hours after eating the offending food

• Associated with rice dishes, cream and milk products, pastas

• Symptoms resolve within 10-24 hours

• Assoc w heat stabile toxin called cereulide

• Endospores can survive normal cooking procedures

• Under conditions of improper storage the spores germinate and the bacteria multiply to produce the toxins that cause the symptoms

clostridium botulinum (bacteria)

• Gram positive spore forming, anaerobic rod

• Found in soil, sediments or lakes and streams, and frequently in intestines of animals

• Over 80 known species of Clostridium--Strains A, E, R, & F are most common

c botulinum intoxication

• Cause by the ingestion of preformed botulinum toxin

• Spores from the organism contaminate meats, vegetables and fish

• Home processed foods are the most common source

  • fruits, chili, stew, spaghetti sauce

• Spores are very heat resistant. Can survive food processing and canning if the temps are not high enough (121 C for 2.5 min or 111 C for 25 min)

• Spores germinate in an anaerobic environment (canned goods)

development of c botulinum intoxication

• Bacteria multiply and produce toxin

• Toxin is formed only during sporulation

• Bacterial growth may cause spoilage, but often the food is unaltered in appearance and taste

• Food is consumed without adequate heating → person gets sick

• Incubation period is 12-36 hours (dose dependent)

• Toxin is inactivated at 80 C (175 F) for 10 minutes

botulism pathogenesis

• Toxin is absorbed through the stomach and enters the blood

• Clinical disease begins within 4-36 hrs after ingestion

  • Time depends on dosage

• Symptoms include:

  • Nausea and vomiting

  • Double and blurred vision

  • Difficulty with swallowing and speaking

  • Weakness of neck and extremities

  • Difficulty with breathing

  • Acute flaccid paralysis of muscles – descends from the head downward

    • face, eyelids, thorax, diaphragm, extremities

• Death usually occurs due to paralysis and respiratory failure

botulinum toxins

• Simple AB toxin that interacts with other bacterial proteins that may protect the AB toxin from stomach acid and proteases, and help it transit the stomach wall

• Once in the bloodstream, it is transported to neuromuscular junctions where it binds to glycolipids on the ends of the peripheral nerves

• A-portion prevents the release of acetylcholine at peripheral nerve synapses

• Nerve impulses can’t be transmitted, no muscle stimulation

• Doesn’t kill neurons, just prevents them from functioning

infant botulism

• First recognized in 1976

• Now the most common form of Botulism in the USA

• Seen most often in infants <20 weeks old

• Spores ingested by infant

  • honey has been implicated in many cases of this

• Spores germinate in gut

• Lack of adult-like normal flora prevents microbial antagonism, thus no natural protection

symptoms of infant botulism

• Colonizes the gut and produces toxin

• Toxin is absorbed and causes disease

• Symptoms

  • Constipation

  • Listlessness

  • Difficulty sucking and swallowing

  • Altered cry

  • Hypotonia

  • Muscle weakness--floppy baby

wound botulism (RARE)

• Spores introduced into deep wounds

• Host tissue consume oxygen

• Spores germinate produce toxin

• Typically seen in black tar heroin and other IV drug users

treatment of botulism

• Antitoxin therapy effective if begun early

• Life support for those severely affected

• Antibiotic therapy to eliminate organism

  • Wound & Gut colonization

• Prevention is the best way to avoid this food poisoning

  • If a can sprays you when you open it, don’t use it

  • Discolored contents

  • Bad odor

clostridium perfringens food poisoning

• Patient ingests organism from contaminated food:

  • Beef, turkey, chicken, pork, gravy

  • Org grows and produces toxin once in the body

• Needs 10^8 viable orgs to reach the small intestine to form toxin

• Toxin A produced

symptoms of c perfringens food poisoning

• Crampy abdominal pain develops 7-15 hours after ingestion

  • Diarrhea w foamy, foul-smelling stools

  • Little vomiting

  • No fever

• Mild, self-limited, 2-3 days to recover

peptic ulcer disease (PUD)

• Caused by Helicobacter pylori

• Associated with stomach cancer, atrophic gastritis, & peptic ulcer disease

• Responsible for 65-90% of gastric ulcers

• Robin Warren & Barry Marshall proved that ulcers were bacterial in nature & won the 2005 Nobel Prize

reservoir for h pylori

• Humans are probably the primary reservoir

  • Org infects stomach epithelium and duodenal epithelium

• Infection rates increases with age

  • In developing countries nearly all adults are infected due to childhood acquisition

  • Percent infected corresponds to age: 10% of 10 yr olds are infected; 20% of 20 yr olds etc

  • In developed countries, infection rates lower but infection still occurs in childhood

(h pylori) transmission/infection

• Fecal-oral is primary route

• Oral-oral transmission may occur

• Transient oral colonization appear to result from either route

• Successful infection appears to require at least a transient low stomach acidity

• Initial survival in the stomach requires bacterial urease

  • Converts urea to ammonia and carbon dioxide

  • Urease negative mutants do not cause disease

• H pylori is a rapid urease producer

(h pylori) damage to gastric mucosa

• Ammonia--toxic to gastric mucosa

• Vacuolating toxin

  • Lethal to epithelial cells

  • Causes acidified vacuoles to form in epithelial cells

  • Unknown mechanism of toxicity

  • Gastric mucosa cells are destroyed

• Urease itself damages the mucosa

(h pylori) host response & symptoms

• Tissue damage stimulates inflammation

• Inflammatory stimuli include tissue damage from ammonia and vacuolating toxin, LPS, and urease

• 50% of cases have bloating, stomach pain, vomiting

• Symptoms develop 3-7 days after infection and resolve within 2 weeks

(h pylori) ulcers & cancer

• Progression to ulcers is dependent upon host genetic factors, bacterial exotoxin, and environmental factors

• Chronic inflammation may damage epithelial and subepithelial tissues to allow penetration of organism into mucosa, leads to gastric ulcer

• Chronic inflammation leads to cancer through cell proliferation and oxidative burst products

  • Cause DNA damage

• These factors increase the likelihood of mutation and hence cancer

treatment for h pylori

• Antibiotics

  • Amoxicillin and metronidazole

  • Drugs must survive the stomach acidity

    • Proton pump inhibitors (PPIs)

    • Bismuth subsalicylate

    • Histamine (H-2) blockers if PPI's cannot be used

  • Also drugs must permeate mucin layer

normal flora of the lower GI tract

• Anaerobes (predominant type found)

• E coli & other enteric GNRs

• Pseudomonas sp and other non-fermenting GNRs

• CNS

• Enterococci

• Yeast

bacillary dysentery

• caused by Shigella species

• Most communicable of the bacterial diarrheal diseases

• Humans and primates are only hosts

• Obligate pathogen

• Uncommon in developed countries

• Endemic in underdeveloped countries

• Does not survive in the environment

• Not NF, although carrier states exist

• Very low dosage, 10-100 orgs required for infection

order of virulence for shigella sp

1. S. dysentariae

2. S. flexneri (found in USA)

3. S. boydii

4. S. sonnei (most common in USA)

disease process of dysentery (shigella)

• Starts as a moderate watery diarrhea with a low-grade fever

• Symptoms change after 24 hours of diarrhea

  • Severe abdominal pain and cramping

  • High fever

  • Low-volume (several hundred mL) that is bright red (from blood) and mucoid (sloughing of intestinal epis)

  • Headache, convulsion, and possible kidney failure

• Generally self-limiting with 5-7 days

incubation period for shigella sp dysentery

12 hours - 6 days; usually 2-4 days

(shigella dysentery) transmission & colonization

• Ingestion of contaminated food or water by direct contact--fecal oral route

• Highly communicable

  • Only need to ingest 10-100 organisms

  • Can survive the stomach acid

• Colonizes the lower small intestine and the colon

• Specific colonization factors are unknown

(shigella dysentery) penetration of bacteria in GI tract

• Organism penetrate the intestinal wall through M-cells of Peyers patches

  • enter cells within an endosome or phagosome

  • M cell translocates organism to underlying macrophage

• Organism can replicate inside the macrophage

  • Trigger apoptosis of the macrophage

  • Bacteria are liberated into lamina propria

(shigella dysentery) SPREAD of bacteria in GI tract

• Liberated organisms invade the basolateral surface of epis

  • Active invasion requires Ipa B and Ipa C proteins

  • Insertion leads to cytoskeleton rearrangements, forms pseudopods

  • Pseudopods engulf organisms forming an endosome

  • Endosome lysed by Ipa B and C

  • Bugs grow free in host cytoplasm

• Bacteria spread from the M cell (cell-cell spread)

  • Ipa and Ics proteins are expressed by organisms growing in the cytoplasm of the cells

• process of cell to cell spread and invasion allows vast sections of the intestinal epithelium to be infected ; this intracellular multiplication causes epithelial cell death

(shigella) Ipa protein function

• Made by Shigella and some E coli allow penetration & spread or organisms through the intestinal epithelium

  1. Ipa proteins (IpaA, B, C) direct reorganization of the epithelial cell cytoskeleton, allowing uptake of the bacterium within a membrane-bound vacuole

  2. IpaB/C directs lysis of the vacuole, allowing organism to enter cytoplasm

(shigella) Ics protein function

1. IcsA directs actin polymerization that push orgs into adjacent cell, where it is surrounded by a double layered vacuole

2. IcsB & IpaB/C lyse the first & second layers of the vacuole respectively, allowing access to adjacent cell's cytoplasm

host response to shigella dysentery

• develops strong inflammatory response due to tissue damage, proinflammatory cytokines released by infected host cells, and presence of bacteria

• Dramatic influx of phagocytes to infection sites damage cohesion of the epithelium and allows more extensive invasion of the epithelium by the org

• Sheets of epithelial cells are sloughed from the intestinal wall due to inflammatory response and microbial action

• Loss of epithelium damages lamina propria and associated blood vessels hemorrhage leading to bloody diarrhea

• Inflammation limits infection to the epithelium and lamina propria

(shigella dysentery) infection clearance

• Tissue and blood defenses

  • Complelement—shigella sensitive to complement except for S dysenteriae

  • Activated macros—orgs don't survive in them

  • Natural killer cells recognize foreign peptides on host cells

• Immune response

  • Antigenicity of orgs--O antigen, Ipa proteins are good antigens

  • Infection is not protective

• Usually lethal to those <5 yrs

• Death from dehydration and septic shock induced by endotoxins

treatment for shigella dysentery

• Provide supportive therapy

  • Hydration

• Antibiotics increase the rate of clearance by reducing the bacterial load

  • Ciprofloxacin

  • Ceftriaxone or azithromycin (2nd line)

• Antibiotics often induced a carrier state

• No effective vaccine against Shigella

(shigella toxins) shigella enterotoxin

• Found in S dysenteriae and S flexneri

• Appear to be pore forming toxins

• Leads to water loss through disruption of ion channels and electrolyte movement into lumen

(shigella toxins) cytolethal distending toxin

• Not present in S sonnei

• Compound AB toxin

• Binds to many cell types

• Causes changes in cytoskeletal structure and inhibition of cell proliferation

• May contribute to diarrhea through loss of tight junction stability

(shigella toxins) shiga toxin (ST)

• Compound AB toxin ; produced by S dysenteriae

• Not required for dysentery; more severe if present

• Released after cell death and lysis

• Attracted to a glycolipid receptor located on certain intestinal epi and endothelial cells, kidney cells, B cells

• Inflammation increases the number of receptors (G3b) due to induction of synthesis of the receptor

• Action is an irreversible inhibition of protein synthesis due to inactivation of 60S ribosomal unit—fatal for the cell

role of shiga toxin in disease

• Toxin lethal for intestinal epithelial cells expressing G3b receptor

• Sections of the intestinal tract not infected with S dysenteriae will still be damaged by the toxin

• Toxin entering bloodstream will damage the intestinal blood vessel

  • damage leads to formation of blood clots which further damages the tissue due to lack of blood

• Toxin is not necessary for the diarrhea, but increases bleeding & abdominal pain/cramping experienced

shigella species bacteria info

• Genetically identical to Escherichia ; DOESN’T WORK ON MALDI

• Kept separate due to diseases each genus causes

• 4 groups--43 serotypes--grouped based on O antigen

• Group A--S dysenteriae

  • Least isolated in the US

  • Most common in developing countries

  • Most virulent

  • 15 serotypes

  • 1 serotype produces Shiga toxin

groups and serotypes of shigella sp

• Group A --S dysentariae

• Group B – S. flexneri

  • 8 serotypes and 9 subtypes

  • Found in US

• Group C – S. boydii

  • 19 serotypes

• Group D – S. sonnei

  • Most common species isolated in the US

  • Has the mildest symptoms

  • 1 serotype

hemolytic uremic syndrome (HUS)

• Rare complication most commonly occurring in children

• Form of acute kidney failure

• Toxin binds to G3b receptor in kidney endothelial cells

  • damages cells triggering clot formation by attracting plts

  • increases number of plt receptors on endothelial cells so more clots keep forming

• Extracellular compounds from NF organisms suppress Shiga toxin production

  • Bacteriodes thetaiotaomicron produces these compounds

• Thus, an imbalance in bowel flora may predispose people to HUS

what is HUS characterized by?

• Thrombocytopenia

• Hemolytic anemia

• Kidney failure

enterohemorrhagic e coli (EHEC)

• Aka E coli O157:H7 based on its serotype

  • Shiga toxin producing E coli (STEC)

• Causes hemorrhagic colitis and HUS

  • O104:H4 also causes HUS

• O157:H7 grows as non-sorbitol fermenter on MAC a sorbitol agar

EHEC symptoms & reservoir

• Get from cows

• Hemorrhagic colitis--bloody diarrhea somewhat similar to dysentery

  • Intense abdominal pain

  • Moderate watery diarrhea that turns bloody

  • NO fever or MUCUS in stool (distinguishes it from dysentery)

transmission of EHEC

• During processing, external surface of meat becomes contamination--when ground up it spreads through the meat

• Orgs are killed by heating to 175 F, if not heated enough live orgs will be ingested

• EHEC are resistant to stomach acid--100 orgs is enough to infect a person

• Can also be transmitted by contact w fomites (diapers), water, improperly cured dried meats, apple cider and unpasteurized milk

(EHEC) colonization/penetration/spread

• Orgs transit to intestine and adhere

  • Loose adherence is mediated by a pilus, called bundle forming pilus (Bfp)

  • Intimate adherence is mediated by the protein Initimin

  • Causes morphological changes in the host cell; deform the microvilli of the cell

  • Loose adherence is required for intimate adherence

  • Intimate adherence is required for diarrhea

• Organisms invade epithelial cells, but not very efficiently

• Does not spread cell to cell like Shigella

EHEC toxins

• Shiga-like toxin (SLT)

  • Structure & action similar to shiga toxin

• Blood in stool appears as a result from toxin production

• Toxin mediated killing damages epithelium and leads to bleeding

• Bleeding occurs mainly in the cecum and ascending colon

• Thrombosis and microvasculature in the lamina propria w necrosis of mucosal villi

• Damage leads to superficial ulceration and pseudomembrane formation

treatment of EHEC

• Antibiotics shorten duration of symptoms and decrease transmission

• Can treat with anti-shiga-like toxin (SLT) antibody is HUS is suspected

non-O157 E coli and HUS

• Other strains of STECs have been shown to cause HUS

  • O26

  • O103

  • O111

  • O128

• Problem bc they are sorbitol positive

cholera (general info)

• Caused by vibrio cholerae

• Several serotypes used to differentiate the strains

  • O antigens composition → O1 and O139 are the most virulent strains

• Caused the 7th (O1) and 8th (O139) pandemics in the 1990s

• Other serogroups are considered avirulent or cause less severe diarrhea

  • Dissimilarity in pathogenic and epidemic potential

  • No cholera toxin produced, but other endotoxins cause the symptoms

cholera in america

• Foci along gulf coast

• Serotype O1 Inaba

• Associated w undercooked crabs and raw oysters

cholera symptoms

• High volume diarrhea

  • Severa liters per day in mild cases; over 20 L/day in severe cases

• Clear to opaque gray-white color –"rice water stool”

• Intestinal contents are washed out, diarrhea consists of water and mucus

• Muscle cramps and dizziness due to loss of electrolytes

• Vomiting may occur but usually no fever

death from cholera occurs from what?

• dehydration (!!)

  • Low blood volume leads to circulatory collapse

  • Fatalities highest in kids under 5

  • Worldwide estimated 100,000 deaths/year

what happens if cholera if non-fatal?

• disease is self-limiting

  • Diarrhea subsides in about 48 hours

  • Mild symptoms may persist for another day

  • Organisms are flushed from the intestine with the diarrhea

  • Toxin poisoned intestinal cells must be sloughed from the mucosa

reservoir of cholera

ubiquitous in nature, found in seawater, colonizes shellfish, esp oysters, crabs, shrimp

transmission & colonization of cholera

• Transmission

  • Organisms ingested with contaminated food or water

  • Contamination could be from infected individuals

  • Organism is sensitive to stomach acid so large quantities are needed → 10^9 to 10^10 orgs

• Colonization

  • Organisms transit to small intestine where they colonize using pili

  • Organism adheres to gastric and intestinal mucosal cells

  • Secretes mucinase – aids in penetration of protective mucin layer

(cholera) cholera toxin

• Compound A-B Toxin

  • Permanently activates ACase, which increases cellular cAMP concentration

  • cAMP activates a protein kinase –A-Kinase

  • A-kinase regulates the activity of ion channels in the membrane

  • Causes ions to move into the lumen of intestine, gradient cause water to move into lumen

  • Efflux overwhelms the water absorptive capacity of the intestine resulting in diarrhea

• **evolutionary link between CF and cholera bc of the CFTR

(cholera) ZOT toxin

• Disrupts the tight junction between intestinal epithelial cells (zona occludens)

• Allows ions to flow into lumen

• Single polypeptide

(cholera) ACE toxin

• Enterotoxin shown to cause diarrhea in animals

• Single polypeptide

• Mechanism is unknown

treatment of cholera

• Rehydration therapy most effective

  • Oral - water, salts, glucose (stimulates uptake in areas least affected by toxin)

  • IV – physiological saline

• Antibiotics – aid in removal of colonized bacteria

• Several brands of Cholera vaccine are available around the world

speciation of vibrio

• Need to speciate vibrio due to variable pathogenicity of each species

• Commercial systems: don’t work bc of the need for salt for all but V cholerae and V mimicus

• Need to use traditional media supplemented w 1% NaCl

• MALDI-Tof

gastroenteritis

• Form of food poisoning

  • Acquired by oral fecal route

  • Bacteria must multiply in host to cause symptoms

  • Most common form of food poisoning

• Campylobacter is most common cause

• Salmonella sp is second most common cause

  • In the US only

symptoms of gastroenteritis

• Initial symptoms develop 12-36 hours after ingestion

• Nausea and vomiting lasting a few hours

• Mild to high fever

• Abdominal pain and diarrhea follow, can last for several days, stool may contain blood

• Severity of abdominal pain depends on host susceptibility/virulence of organism

(gastroenteritis) vibrio parahemolyticus

• Follows ingestion of contaminated seafood

• Produces a hemolysin that is both cytotoxic and cardiotoxic

• Mild to moderate disease

  • Usually, self-limiting 2-3 day duration

• Symptoms

  • Watery, sometimes bloody diarrhea

  • Cramps, nausea

  • Vomiting

  • Headache

  • Low grade fever, chills

(gastroenteritis) aeromonas hydrophilia

• Strong evidence supporting Aeromonas as causative agent of diarrhea, although the data is not absolute

• Produces a cholera like extractable toxin that causes watery diarrhea

• 20% of those w Aeromonas infection had symptoms

(gastroenteritis) plesiomonas shigelloides

• Mild, watery, diarrhea, no blood or mucous

• Often associated with shellfish, oyster or untreated water consumption

• Pathogenicity associated w enteropathogenic enterotoxin

(gastroenteritis) campylobacter jejuni

• Slender, spirally curving to s-shaped or gull wing shaped GNRs

• Microaerophilic and capnophilic

• C jejuni is the most important species and most commonly isolated

  • Worldwide distribution

  • Recovered 2-7x more frequently than S&S (salmonella & shigella) in industrialized countries

(gastroenteritis) campylobacter coli

• Occasional cause of gastroenteritis

• Prefers pigs as hosts

• 5-10% of Campylobacter infections are C coli

• Difference is just the hippurate hydrolysis reaction (neg)

• MALDI-Tof

(campylobacter enteritis) signs & symptoms

• Crampy abdominal pain

• Bloody diarrhea

• Chills, fever

(campylobacter enteritis) reservoir & transmission

• Reservoir: cattle, swine, poultry, waterfowl, house pets

• Transmission

  • Contaminated food--improperly cooked meat; unpasteurized milk

  • Low dosage--about 500 organisms

  • Direct contact with human carriers

    • Infected people may excrete the org for up to a month after symptoms have disappeared

  • Contaminated water

(campylobacter enteritis) colonization

• Infects ileum and colon

• Unknown adherence factors, but functional flagella are required

• Org produces an enterotoxin that is responsible for the diarrhea

  • Enterotoxin activates host adenylate cyclase

(campylobacter enteritis) invasion & spread

• Invade the intestinal mucosa

• Multiply in lamina propria

• Infections restricted to intestinal tract

• Occasional septicemia will occur

(gastroenteritis) clearance of campylobacter

• Inflammatory response kills orgs (phagocytes)

  • Inflammation is responsible for symptoms

• Infection is usually self-limiting (resolves in 3-7 days)

• Antibiotics are administered only if patient becomes septic

• Org can be excreted for up to 1 month following abatement of symptoms

salmonella gastroenteritis

• Common cause of gastroenteritis in the US

• Causes enteric disease ranging from self-limited gastroenteritis w mild symptoms to typhoid fever, infections are usually not fatal

• Moderate to severe GI symptoms

• Diarrhea may be bloody

• Symptoms appear 7-72 hours after ingestion of organism

(salmonella gastroenteritis) reservoir & transmission

• In many animals, fowl, particularly poultry; farm animals

• Direct transmission can occur from symptomatic individuals or carriers or animals (pet turtles)

• Transmitted by contaminated food & water

• Dairy products

  • Salmonella colonizes intestines of chickens

  • Eggs can become contaminated either via transovarian spread or on the surface after laying

  • Meat becomes contaminated during processing

• Human disease results from ingesting uncooked meat or raw eggs

  • can occur from cross contamination of cutting boards, bowls etc

(salmonella gastroenteritis) colonization & invasion

• Not resistant to stomach acid thus needs 10^6-10^8 orgs for disease

  • MUCH more than Shigella sp

• Organisms transit to large and small intestine

• Actively invade the intestinal epithelium thru columnar absorptive cells and M cells

  • Multiplication leads to death of the cells

• Bugs released at the basolateral surface into lamina propria

• Encounter complement and phagocytic cells

(salmonella gastroenteritis) resistance in salmonella

• long LPS chain confers complement resistance

  • MAC forms too far from the bacterial surface

  • Absent LPS strains are avirulent; short LPS strains are less virulent

• Can survive in macros by inducing a set of proteins for survival

  • EnvZ--sensor kinase that response to intracellular osmotic stress, phosphorylated OmpR

  • OmpR--a DNA binding protein that regulates protein expression

• These proteins helps the organism survive both the O2 dependent and O2 independent mechanisms

• Allows the bacteria to multiply in the macrophages

(salmonella gastroenteritis) spread and clearance

• Bacteria usually stay within the lamina propria and epithelium

• Can cause systemic infections if they invade the bloodstream

  • Infants / Immunocompromised

  • Mortality only 2% in treated cases

• Organisms stimulate a strong inflammatory response and strong induced immune response

• Responses limit the spread of infection

• The org can't survive inside activated macrophages

• Inflammatory response is responsible for abdominal pain

(salmonella gastroenteritis) treatment of salmonella

• Usually self-limiting, and only requires antibiotic treatment in certain situations:

  • If infection becomes systemic

  • Carrier state develops

• Site of carriage is unknown (gallbladder?)

• 35-40% of those infected become short term carriers (months)

• 1-4% of those infected become long term carriers (up to a year)

(salmonella gastroenteritis) prevention

• Proper food handling

• Salmonella is killed at temps high enough to denature proteins

• Vaccines and treatments for chickens to prevent colonization

• Improved meat processing techniques at processing plants

tribe salmonelleae

• Most complex tribe even though there is only one genus and two species

  • S enterica (USA) and S bongori

• Most ID systems just indicate that you have isolated a Salmonella species

• clinical lab will perform limited serotyping for the O antigens

  • Organism is reported as Salmonella, Group B, or C1 or C2, or D, or E (NOT typhi, can be added)

• Send to state health lab for complete serotyping

salmonella serological typing

• Mainly done in the lab for Salmonella and Shigella; also done on some E coli

• O antigens (somatic) heat stabile

• K antigens (capsular) heat labile

  • Salmonella K antigens are known as Vi AGNs

  • May interfere with expression of O antigens

  • If it doesn't type, boil org and retest the O antigen tests

• H antigens (flagellar) heat labile

e coli gastroenteritis (general)

• Pathogenic and nonpathogenic forms of E coli exist

  • Non-pathogenic forms are NF—predominant species in the gut

  • Pathogenic forms are not NF

• E coli strains are based on serotypes--pathogenicity not associated w specific serotypes

• O antigens [somatic antigens]

• H antigens [flagellar]

• If E coli is suspected of being the cause of the disease, serotyping is often used for diagnosis

list of pathovars of e coli (5)

1. EIEC (entero-invasive)

2. ETEC (toxigenic)

3. EHEC (hemorrhagic)

4. EPEC (pathogenic)

5. EAEC (aggregative)

(e coli gastroenteritis pathovars) EIEC (enteroinvasive)

• Same as shigella flexneri but not acid tolerant

  • transmission same; dosage is 10^6 orgs

  • infection of M cells & spread same

  • identical virulence factors

• Causes disease identical to dysentery

• Humans = only known reservoir

• Colonization is by pili attaching to intestinal tract cells

• EIEC strains do not produce Shiga toxin = no HUS

• EIEC strains are LDC neg and almost all are non-motile

• Treatment same as shigella dysentery

(e coli gastroenteritis pathovars) ETEC (enterotoxigenic)

• Montezuma's revenge

• Disease ranges from mild water diarrhea to severe diarrhea that is nearly identical to cholera

• Reservoir is humans

• Transmission = fecal oral route ; need 10^6 orgs to cause infection

• Small intestine is colonized using pili

ETEC in developed vs developing countries

• Endemic in developing countries

  • Causes 1.5 million deaths/year worldwide

  • 800,000 of those deaths are in children <5 yrs

  • Death due to dehydration

• In developed countries:

  • Associated w limited outbreaks

  • Usually not fatal

  • Aka traveler's diarrhea

ETEC (toxigenic) toxins

• LT toxin—heat labile toxin

  • Structurally and functionally similar to cholera toxin

  • Compound AB toxin

• ST toxin--heat stable toxin

• Because LT and ST recognize different receptors a wider range of host cells will be poisoned

(e coli gastroenteritis pathovars) EPEC (enteropathogenic)

• Serotypes implicated are O35 and O111

• Generally mild to moderate diarrhea, but can be severe, cholera like

• Infant mortality rate as high as 70% in undeveloped countries

• ID’d by serology

• Infections are usually self-limiting but can be treated w antibiotics

• Humans are the only reservoir

• Transmission by fecal-oral route

  • Need 10^6 orgs to cause infection

• Organisms can invade the epithelium, but they really aren't that invasive

• No known enterotoxins

(e coli gastroenteritis pathovars) EAEC/EAggEC (enteroaggregative)

• Recently identified as pathogenic

• Associated with a mild persistent diarrhea in children

• Form dense clumps of bacteria on the surface of the epithelial cells

• Binding is mediated by fimbriae

• Found to produce heat stable toxin—not sure if it has role in the disease

• Does not lead to HUS

(gastroenteritis) yersinia sp

• GNR w 3 pathogenic speicies

  • Y pestis--bubonic and pneumonic plague

  • Y pseudotuberculosis--gastroenteritis (not common is US)

  • Y enterocolitica--gastroenteritis (common in US)

• Both pathogenic and non-pathogenic (lack virulence factors) strains

(gastroenteritis) yersinia enterocolitica

• Most prevalent in Scandanavia, Europe, Canada, and some parts of the USA

• Produce a heat stable toxin

  • Similar to that produced by E. coli

  • Makes it invasive

• 1988 – Outbreak associated with eating chitterlings

  • cleaned/boiled pig intestines

• Assoc w transfusion acquired sepsis because it can tolerate the cold