BAHAN KULIAH ENTERIK

7/28/2019 BAHAN KULIAH ENTERIK

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Enterobacteriaceae


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Enterobacteriaceae Small gram-negative rods (2-5 by 0.5 microns) Most motile with peritrichous flagella

Shigella and Klebsiella are nonmotile Oxidase-negative facultative anaerobes Reduce nitrate Ferment glucose and other carbohydrates

Lactose fermenting strains (e.g. Escherichia, Klebsiella,

Non-lactose fermenting (e.g. Salmonella, Shigella, andYersinia)

Many generaEscherichia, Salmonella, Shigella, Klebsiella, Proteus,

Enterobacter, Yersinia, etc. Some strains opportunistic pathogens Some strains true pathogens

Salmonella, Shigella, Yersinia, some strains ofE. coli


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Enterobacteriaceae

Opportunistic pathogensEscherichia coli

Klebsiella pneumoniae

Enterobacter aerogenes

Serratia marcescens

Proteus spp.

Sepsis

Meningitis

Diarrhea

Pneumonia

Providencia spp.

Citrobacterspp.

Obligate pathogens

Salmonella spp.

Shigella spp.

Yersinia spp.

Some E. colistrains

UTI


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Enterobacteriaceae is characterized biochemically by the

ability to reduce nitrates to nitrites and to ferment glucose.

Cytochrome oxidase-negative.

Enterobacteriaceae species differ in their ability to ferment

lactose. Some ferment lactose rapidly, some does it slowly

and the others (e.g., Salmonella and Shigella) do not

ferment lactose at all.

Some Enterobacteriaceae pathogens (e.g., Salmonella and

Shigella) are resistant to bile salts, and this property can be

used to select them from commensal organisms that are

inhibited by bile salts.


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Antigenic Structure

O antigens

O-specific polysaccharides located in LPS. Heat-stable andresistant to alcohol. A single organism may carry several O

antigens.

(Core polysaccharide of LPS: enterobacterial common antigen,

ECA.)

an gens

External to O antigens in some strains. Mostly are capsular

antigens (polysaccharides). K antigens ofKlebsiella can be

identified by capsular swelling test.

H antigen

Flagellin. Heat-labile and denatured by alcohol. May be absent

or undergo phase variation in different species.


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ECA


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Toll-like

receptor 4(TLR-4)

Pathogenesis of sepsis causedby gram-negative bacteria


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Pathophysiological effects of LPS

Activation of complement, release of cytokines,

fever, leukocytosis, thrombocytopenia, impairedorgan per us on an ac os s, ssem na e

intravascular coagulation (DIC), hypotension,

shock and death, premature labor and abortion.


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ENDOTOXIN

1. Integral part of cell wall

2. Endotoxin is LPS; Lipid A is

toxic component

3. Heat stable

EXOTOXIN

1. Released from the cell before

or after lysis

2. Protein

3. Heat labile

4. Antigenic; ??immunogenicity

5. Toxoids cannot be produced

6. Many effects on host7. Produced by gram-negative

organisms only

4. Antigenic and immunogenic

5. Toxoids can be produced

6. Specific in effect on host7. Produced by gram-positive

and gram-negative

organisms


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Escherichia

10


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Biological properties Shape and structure

Motile

pili

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Biological properties Chemical reactioncarbohydrate fermentation, producegas and acid

lactose fermentation positive

12

IMViC ++--


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Escherichia coli

Serology ofE.coli:

According to the cell wall (O antigen)

over 160 types recognized.

According to the flagellar (H antigen) 55

types.

Making over 8000 possible O-H seotypes.

Some E.colitypes are capsulated


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Escherichia coli

Sepsis

For people with inadequate host defenses, e.g. the newborns.

Usually originates from UT or GI infections. Some infections

may be endogenous.

Pathogenesis and clinical diseases

E. coli (particularly

K1 strains) and

S. agalactiae are

the leading causes

of meningitis in

infants.

Bacteremia


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Urinary tract infection

E. coliis the most common cause of urinary tract infection.

Community- vs. hospital-acquired UT infection

Most infections originate from colon; the bacteria

Escherichia coli


contaminate the urethra, ascend into the bladder, and may

migrate into the kidney or prostate.

Symptoms: urinary frequency, dysuria, hematuria, and

pyuria. Can result in bacteremia and sepsis.

Uropathogenic E. colistrains produce P (Pyelonephritis-

associated) pili, which is associated with renal colonization

and may induce protective immunity, and hemolysin HlyA.


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Pathogenic strains

1. EPEC ( Enteropathogenic )

2. ETEC ( Enterotoxigenic ).

4. EHEC( Enterohaemorrhagic )

5. EAEC ( Enteroadherent )


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Escherichia coli


Enterotoxigenic E. coli(ETEC): major causal agent of Traveler's

diarrhea.

These strains express:

a) Heat-labile (LT-1) enterotoxins: an A-B toxin. Subunit A causesn ense an pro onge yper secre on o c or e ons an n s

the reabsorption of sodium and chloride. The gut lumen is distended

with fluid, and hypermotility and secretory diarrhea occur, lasting for

several days. It stimulates the production of neutralizing antibodies,

and cross-reacts with the enterotoxin ofVibrio cholerae.

b) Heat-stable (STa) enterotoxin: also stimulates fluid secretion;

poorly immunogenic; short onset.

c) Colonization factors (CFAs): facilitate the attachment ofE. coli

strains to intestinal epithelium. Usually are pili in nature.


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Enterotoxigenic E. coli (ETEC)Produced Enterotoxin.

Plasmid mediated enterotoxin production.

There are 2 kind of Toxins :

Lt ( Labile toxin )

St ( Stable toxin)


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Lt ( Labile toxin )

Big Molecule.

Antigenic.

Cross reaction with Cholera toxin.

Cascade reaction-end product cyclic -5-AMP ( Adenosine Mono Phosphate )

Profuse watery diarrhea.DehydrationElectrolyte and Acid-Base

derangementmetabolic acidosis renalfailure death.


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Stable toxin (St)

Smaller molecule

Non Antigenic.

Activate Guanylate cyclase

enzyme systemcascadereac onen pro uc cyc c GMP (Guadenosin Mono Phosphate )Low quality energy resouces mild

diarrhea.


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Enteropathogenic E coli (EPEC)

Causes infant diarrhea in poor countries.

Attachment to immature intestinal mucosalcells Destruction of mucosal villi

Watery diarrhea results from malabsorptiondue to microvilli destruction. Spread by person-to-person contact

Causing diarrhea followed by fever and icteric

Fatal infection especially on neglected labor.


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Enteroinvasive Escherichia coli(EIEC)

Site of infection mucosal cells layer of Colon.

Shigella like infection.

Closely related to Shigella in pathogenic

properties.

Shiga like toxin toxic to colonic mucosal

cells- necrosisulcersbleeding ( Bloodeddiarrhea), fever tenesmus ani ( TriasBacillar Dysentery)


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Escherichia coli

Pathogenesis and clinical diseasesEnterohemorrhagic E. coli(EHEC)

The most common strains producing disease in developed countries.

These strains are associated with hemorrhagic colitis and hemolytic

uremic syndrome (HUS: acute renal failure, microangiopathic- .

Serotpe O157:H7 is most commonly isolated.

Cattle is a reservoir, and hamburger, unpasteurized milk, fruit juices,

and uncooked vegetables are common sources of human infection.

Induces A/E lesions on enterocytes. Diarrhea and HUS may be

associated with the Shiga toxins, which are A-B toxins that bind to

28S rRNA and disrupt protein synthesis.


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Enteroadherent E coli

Multilayer colonization on intestinalmucose.

Biofilm formation

.

Malabsorbtion syndrome.

Enteroaggregative E. coli(EAEC):causes chronic diarrhea and growthretardation in infants in developingcountries.


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KlebsiellaK. pneumoniae and K. oxytoca are the most commonly isolated.

Can cause community-acquired primary lobar pneumonia

(frequently involves necrotic destruction of alveolar space), and

infections of wound, soft tissue, and urinary tract.

Risk factors for pneumonia: alcoholism; compromised pulmonary

Other opportunistic Enterobacteriaceae

function.

*In Taiwan: liver abscess is commonly seen in infection by K.

pneumoniae.

K. granulomatis may cuase granuloma inguinale, a sexuallytransmitted disease, in some countries.

K. rhinoscleromatis: granulomatous disease of the nose.

K. ozaenae: chronic atrophic rhinitis.


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ProteusMost common isolates: P. mirabilis.

Cause urinary tract infections and bacteremia.

Produce urease, making the urine of the patients ofUT

infection with Proteus alkaline, promoting stone formation

by precipitating Mg and Ca.

Enterobacter, Citrobacter, Morganella, Serratia

Opportunistic pathogens causing nosocomial infections in

neonates and immunocompromised patients.

These genera, particularly Enterobacter, are resistant to

multiple antibiotics.


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Yersinia

Y. pestis: plague ("black death")

Y. pseudotuberculosis and Y. enterocolitica: gastroenteritis

Grows more rapidly in media containing blood or tissue fluids

and fastest at 30 oC. Some species (e.g. Y. enterocolitica) can

grow in refrigerated food.

Patho enesis

The Yersinia pathogens are able to resist phagocytic killing by

secreting proteins into the phagocyte and result in inhibition of

killing by phagocyte, apoptosis of macrophage, and suppression

of cytokine production.

Y. pestis produces a protein capsule (Fraction 1), and Pla

(plasminogen activator protease) that degrades C3b and C5a,

and fibrin clot (enhances spread of bacteria into blood stream).


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Yersinia pestis

Causes zoonotic infections; humans are accidental hosts.Three major pandemics have occurred in 541 AD, 1320s and 1860s.

Two forms of infections:

Urban plague

Rats as natural reservoirs.Spread among rats or between rats and humans by infected flea.

Can be eliminated by effective control of rats and better hygiene.

Sylvatic plague: infections of rodents and domestic cats.

Y. pestis are widely distributed in mammalian reservoirs and fleavectors and produces fatal infections in animal reservoirs.

Human infections are acquired by contacting the reservoir

population.


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Yersinia pestis

Pathogenesis

Bubonic plague

Y. pestis enters a flea when it feeds on an infected animal the

bacteria multiply in the gut of the flea flea becomes hungry and

bites ferociously Y. pestis passes from the flea into the bite

wound the bacteria are phagocytised, but can multiply,

intense hemorrhagic inflammation develops in the enlarged lymph

nodes, which may undergo necrosis Y. pestis may reach the

bloodstream and become widely disseminated. Hemorrhagic and

necrotic lesions may develop in all organs.Primary pneumonic plague

Results from inhalation of infective droplets (usually from a

coughing patient), with hemorrhagic consolidation of the lung,

sepsis and death.


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Yersinia pestis

Clinical Diseases

Bubonic plague

Incubation period: 2-7 days.

High fever and painful lymphoadenopathy with greatly

enlarged, tender lymph nodes (buboes) in the groin and axilla

hypotension, renal and cardiac failure; terminal stage:

pneumonia and meningitis). Mortality: 75% if untreated.

Pneumonic plague

Incubation time: 2-3 days.

Fever and malaise, pulmonary signs develop within 1 day.

Patients are highly infectious. Mortality: 90% if untreated.


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Yersinia pestis

TreatmentPatients have to be promptly treated with antibiotics (drug of

choice: streptomycin).

Epidemiology and control

Plague is an infection of wild rodents that still occurs in many

parts of the world (enzootic areas: India, Southeast Asia, Africa,

and North and South America).

Control of plague requires surveys of infected animals, vectors,

and human contacts, and by destruction of infected animals.

All patients with suspected plague should be isolated.

Contacts of patients with suspected pneumonic plague should

receive tetracycline as chemoprophylaxis.


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Salmonella

Epidemiology

S. Typhi and S. Paratyphi are primarily infective for humans.

Other salmonellae are chiefly pathogenic in animals (poultry, pigs,

rodents, cattle, pets etc.) that constitute the reservoir for human

infection.

or drink (mean infective dose: 106-108, but that ofS. typhiis lower).

In children, infections can result from direct fecal-oral spread.

The most common sources of human infections: poultry, eggs, dairy

products, and foods prepared on contaminated work surfaces.

However, the major source of infection for enteric fever is the

carriers (convalescent or healthy permanent).


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Salmonella

Salmonella spp. do not ferment lactose.

Most species ofSalmonella are motile with peritrichous flagella.

Some Salmonellae have capsular antigens; that ofS. Typhi is

referred to as Vi antigen.

Grou s and s ecies ofSalmonella are identified b serolo ic

analysis of O and H antigens (> 2,500 serotypes). Classification of

salmonellae is traditionally based on serogrouping and serotyping

(e.g. S. typhimurium, which is reclassified as S. enterica together

with most human pathogens by analysis of DNA homology). Thecorrect name forS. typhiis S. enterica, serovar. Typhi orS. Typhi.

They can be identified by biochemical tests and serogrouping, with

follow-up serotyping confirmation.


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Salmonella

Pathogenesis and Immunity

Invasion

Acid tolerance response (ATR) gene protects the organism

from gastric acid.

The bacteria invade into (by inducing membrane ruffling)

and multi l in the M cells of the small intestine.

Inflammatory response confines the infection to the GI tract.

Survival in macrophages

Salmonellae are facultative intracellular pathogen.


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Salmonella

Clinical diseases

1. Enteritis

Incubation period: 6-48 hours.

, , ,

profuse diarrhea, with few leukocytes in the stools. Low-

grade fever, abdominal cramp, myalgia, and headache

are also common. Episode resolves in 2-7 days.

Inflammatory lesions of the small and large intestine are

present. Stool cultures remain positive for several weeks

after clinical recovery.


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Salmonella

Clinical diseases

3. Enteric fever (typhoid fever)

Causal species: S. Typhi, S. ParatyphiA, S. Schttmuelleri,

and S. Hirschfeldii.

Mouth small intestine lymphatics and bloodstream

infect liver, spleen and bone marrow multiply and

pass into the blood second and heavier bacteremia

onset of clinical illness colonization of gallbladder

invasion of the intestine typhoid ulcers and severe

illness.

Chronic carriers (1%-5% of patients): bacteria persist in the

gallbladder and the biliary tract for more than one year.


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Symptoms: incubation time: 10-14 days.

Gradually increasing fever, malaise, headache,

myalgias, and anorexia, which persist for a week

or longer.

perforation.

Principal lesions: hyperplasia and necrosis of

lymphoid tissue, hepatitis, focal necrosis of the

liver, and inflammation of the gallbladder,

periosteum, lungs and other organs.


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Salmonella

TreatmentEnteric fever and bacteremia require antibiotic treatment:

chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole.

Surgical drainage of metastatic abscesses may be required.

Salmonella enterocolitis needs only supportive therapy

excretion of the salmonellae). Drugs to control hypermotility

of the gut should be avoided because it is easy to transform

a trivial gastroenteritis into a life-threatening bacteremia by

paralyzing the bowel.

Chronic carriers ofS. Typhi may be cured by antibiotics alone

or combined with cholecystectomy.


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SalmonellaPrevention and control

Sanitary measures.

Carriers must not be allowed to work as food

handlers.

Strict hygienic precautions for food handling.

Vaccines against S. Typhi:

Purified Vi antigenOral, live attenuated vaccine.


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ShigellaS. dysenteriae, S. flexneri, S. sonnei, & S. boydii: bacillary dysentery

> 45 O serotypes; have no H antigen; do not ferment lactose.

Pathogenesis and Immunity

Shigellosis is primarily a pediatric disease, and is restricted to the GI

tract.

Mean infective dose: 103.

Mouth colon invade M cells and subsequently spread to

mucosal epithelial cells cause microabscess in the wall of colon

and terminal ileum necrosis of the mucous membrane,

superficial ulceration, bleeding, and formation of pseudomembrane.

Shiga toxin

An A-B toxin inhibiting protein synthesis.

Damages intestinal epithelium and glomerular endothelial cells

(associated with HUS) .


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Destablize the

intestinal wall

Activates the invasion genes

on the virulence plasmid

M cell

Internalized shigellae induce

apoptosis of macrophage

and release of the bacteria

Attracted by

the cytokines

released by

macrophage


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Shigella

Clinical diseases

Incubation period: 1-3 days

Sudden onset of abdominal pain, fever and watery diarrhea

number of stools increase, less liquid, often contain mucus

,

(tenesmus) symptoms subside spontaneously in 2-5 days

in adult cases, but loss of water and electrolytes frequently

occur in children and the elderly a small number of

patients remain chronic carriers.

Some cases were accompanied by hemolytic uremic

syndrome (HUS).


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Shigella

Prevention and control

Humans are the only reservoir for shigellae.

Transmission of shigellae: water, food, fingers, feces,

and flies.

Most cases occur in children under 10 ears of a e.

Prevention and control of dysentery:

1. Sanitary control of water, food and milk; sewage

disposal; and fly control.

2. Isolation of patients and disinfection of excreta.

3. Detection of subclinical cases and carriers.

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BAHAN KULIAH ENTERIK