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Gram-Negative Rods Related

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• Second level
To the Enteric Tract
• Third level  
• Fourth level
THE ENTEROBACTERIACEAE
• Fifth level

By:

Dr. Rania Ahmed

Assistant professor of Medical Microbiology and Immunology
Ain Shams University
• It is a large family of Gram-negative rods.

• Enterobacteriacae family includes many genera as:

Escherichia
Klebsiella, Enterobacter, Serratia
Proteus, Providencia, Morganella
Salmonella
Shigella
Yersinia.
Natural Habitat:
1. The majority are present as the normal flora in the colon of both
man and animals (e.g. E. coli).
2. Some are saprophytes in water, soil and plants (e.g. Proteus) .
3. Few of them are primarily intestinal pathogens (e.g. Salmonella &
Shigella )
General Characteristics of
Enterobacteriaceae Family:
• They are Gram-negative non spore forming,
non-capsulate with few exceptions.

• They are motile with peritrichate flagellae

with few exceptions.

• They can grow on ordinary media as well as

on selective and differential media e.g.
MacConkey’s agar
 General Characteristics of
Enterobacteriaceae Family:
• According to growth on
MacConkey’s agar
They are classified into:
Lactose fermenting e.g. E coli
and Klebsiella
Non- lactose fermenting e.g.
Proteus, Salmonella and
Shigella
Late lactose fermenters
 General Characteristics of
Enterobacteriaceae Family:
 

• They have 4 common characteristics:

• Facultative anaerobe.
• Ferment glucose
• Oxidase negative but catalase positive.
• Reduce nitrate to nitrite.

• Differentiated by biochemical reactions & antigenic structure.

 

 
Antigenic structure:
• Three surface antigens (O, H & K):
• O antigen (somatic antigen) is the outer
polysaccharide portion of the
lipopolysaccharide.
• H antigen is the flagellar antigen.
• K antigen is the capsular antigen.
 ESCHERICHIA
• This genus contains five species, the most important of which is
Escherichia coli ([Link]).

• Important Properties:
• E. coli is a straight Gram negative bacilli, motile, may be capsulated.
• 
• E. coli ferments lactose, a property that distinguishes it from the two
major intestinal pathogens, Shigella and Salmonella.
Normal habitat:
• Gut of humans and animals; it is the most
abundant facultative anaerobe in the colon and
feces.
• It may colonize lower end of urethra and vagina.
 The antigenic structure:

Virulence Factors:
• Pili. • Exotoxins (enterotoxins).
• Capsule. • Motility.
• Endotoxin.
Diseases caused by [Link] :
1. Urinary tract infection (UTI) :caused by uropathogenic E. coli
[Link] is the most common cause of UTI.
 
2. Neonatal meningitis: caused by [Link] strains having K1 capsular antigens
 
3. Different types of healthcare associated infections (HAIs) e.g. surgical site infections (SSI),
catheter associated UTI (CAUTI), ventilator associated pneumonia (VAP), and intravascular
device associated infections.
 
4. Diarrhea: caused by certain strains known as diarrheagenic E. coli.
 
Pathogenesis of [Link] infections:
Source of the E. coli

• Diarrhea  is acquired by ingestion of food or water contaminated

with human feces.
• Urinary tract infections  the patient’s own colonic flora that
colonizes the urogenital area.
• Neonatal meningitis  the mother’s birth canal; the infection is
acquired during birth.
 Pathogenesis of Diarrhea:
1. Enterotoxigenic E. coli
(ETEC):
Produces two enterotoxins: The heat-
labile & heat stable toxin (LT):
 
The heat-labile toxin (LT)  stimulate
adenylate cyclase  ↑intracellular
cAMP  outpouring of fluid, K+ , Cl- from
the enterocytes into the lumen of the gut
 Watery diarrhea.
 
heat-stable toxin (ST)  stimulate
guanylate cyclase ↑ intracellular cGMP
 Watery diarrhea.
 
 Pathogenesis of Diarrhea:
2. Enterohaemorrhagic E. coli (EHEC):
Produce Shiga- like toxins called
verocytotoxins (VT) similar in action to Shiga
toxin: Inhibit protein synthesis.  Bloody
diarrhea.
 Pathogenesis of Diarrhea:
3. Enterpathogenic E. coli (EPEC):
EPEC adhere to the mucosal cells of small intestine by pili, resulting in
destruction of the microvilli  electrolyte imbalance and watery diarrhea.
Pathogenesis of Diarrhea:
4. Enteroinvasive E. coli (EIEC):

EIEC cause disease dysentery –like

syndrome.
Virulence factors are nearly identical
to Shigella species; that allow the
invasion of mucosal epithelial cells of
the large intestine and intracellular
spread Tissue destruction
diarrhea, blood, mucous, and painful
abdominal cramps
 Pathogenesis of Diarrhea:
5. Enteroaggregative E. coli (EAEC): they are characterized by specific pattern of adherenc to
intestinal cells in an aggregative manner by aggregative adherence fimbriae and production of
heat stable (ST)-like toxin.
EAEC causes traveler's diarrhea and persistent diarrhea in children.
Pathogenesis of Neonatal meningitis &
sepsis:
• [Link] strains with K1 capsular antigen acquired by neonate
through passage in birth canal invade the blood stream of
infants from the nasopharynx or gastrointestinal tract
causing sepsis and meningitis.
Pathogenesis of Urinary Tract Infections:
The bacteria colonize the periurethral area then ascend the urinary
tract to cause UTI.
• Pili  bind to specific receptors on the urinary tract epithelium.
• Motility aids to ascend from:
• Urethra into the bladder.
• Ureter into the kidney.
 KLEBSIELLA
Important Properties:
• Short Gram-negative rods, facultative anaerobes,
non-motile, with very large polysaccharide capsule.
• They can be found in water, soil, plants, insects,
animals and humans.
• Habitat: is the human large intestine and upper
respiratory tract.

Antigenic Structure:
• O antigen. K antigen.
 KLEBSIELLA
Species:
• Two species produce diseases in man; can be differentiated by their
capsular antigens.

1. Klebsiella pneumoniae:
• The most common species responsible for majority of Klebsiella
infections.
• Includes 4 subspecies (they are sometimes called K. pneumoniae, K.
aerogenes, K. ozanae, K. rhinoscleromatis).
2. Klebsiella oxytoca
Diseases caused by Klebsiella :
1. Community-acquired pneumonia: Necrosis, inflammation, and hemorrhage
occur within lung tissue, sometimes producing thick, bloody, mucoid sputum
described as currant jelly sputum (Fried-Lander pneumonia)

The illness typically affects middle-aged and older men with debilitating
diseases such as alcoholism, diabetes, or chronic bronchopulmonary disease.

2. Health care associated infections (majority of Klebsiella infections) e.g.

pneumonia, UTI, and SSI

3. Neonatal bacteremia & septicemia especially among premature infants and in

neonatal intensive care units.
Transmission of Klebsiella causing
infections:
• Organism is transmitted to the lungs by aspiration from upper
respiratory tract or by inhalation of respiratory droplets.

• It is transmitted to urinary tract by ascending spread of fecal flora.

• It is transmitted in hospitals by contact by contaminated hands of

surrounded people in the hospitals or contact with contaminated
equipment in hospitals e.g. catheters, respiratory devices.
 Virulence factors of Klebsiella:
1. The huge polysaccharide capsule: It is the main virulence
factor. It is antiphagocytic.

2. Lipopolysaccharides (LPS): fever and shock associated with

sepsis.

3. Adhesins: These may be fimbrial or non-fimbrial. These

help the microorganism to adhere to host cells.
 PROTEUS SPECIES
Important properties:

Short Gram-negative rods, highly motile.

High motility produces a striking swarming effect on some culture
media as blood agar.
They produce the enzyme urease, which cleaves urea to form
ammonia & CO2.

These organisms are found in soil, water and human colon.

 PROTEUS SPECIES
Virulence factors:

The flagellum: vigorous motility of Proteus organisms

may contribute to their ability to invade the urinary
tract.
Pili: responsible for adhesion.
Endotoxins: responsible for induction of the
inflammatory response.
 PROTEUS SPECIES
Mode of transmission:
• Proteus spp. are part of the human intestinal flora and can cause
infection upon leaving this location.
• They may also be transmitted through contaminated catheters
(particularly urinary catheters).

Diseases:
• These organisms primarily cause urinary tract infections, both
community- and hospital-acquired.
• Other infections: septicemia and wound infections.
 SALMONELLA
Important characters:

• Gram-negative, motile non-sporing rods, non capsulated

except Salmonella typhi (S. typhi) and [Link] C
which possess Vi antigen.
 SALMONELLA
Natural Habitat:
• All salmonellae are obligate parasites.

• S. typhi: Man is the only reservoir.

Other species of salmonellae have a significant animal as well as
human reservoir:
• The most frequent animal source is poultry and eggs of animals.
 SALMONELLA
Antigenic structure:
It displays 3 antigens cell wall O, flagellar H, and
capsular Vi.
Salmonellae are divided into serogroups according to O
(somatic) antigens and then into serotypes according to
specific H (flagellar) antigens.

Some possess Vi (capsular) antigens.

 SALMONELLA
Virulence factors:
• Fimbriae: attachment to host cells.
• Intracellular pathogen: can survive & multiply within
macrophages.
• Capsule (Vi): of S. typhi and [Link] C, which is
antiphagocytic.
 SALMONELLA
Virulence factors:
• Phase variation of H antigens, which varies from group
specific (phase II) to species specific (phase I).
• This variation helps the organism to evade the immune
system.
 Infections caused by Salmonella:
• Enteric fever caused by Salmonella typhi (typhoid fever) & S. paratyphi A,
B and C (paratyphoid fever).

• Salmonella food poisoning (Salmonella enterocolitis) is caused by S.

typhimurium and S. enteritidis.

• Bacteremia with focal lesions in lungs, meninges, and bones is caused by

S. choleraesuis.
Pathogenesis Of Enteric Fever:

Mode of transmission

• Ingestion of contaminated food or water by the excreta of a case or a carrier

(fecal or urinary carrier).

• Occasionally through direct contact with patients or carriers.

Pathogenesis Of Enteric Fever:

Onset of
disease
Pathogenesis Of Enteric Fever:

Carrier
Salmonella Food Poisoning "Salmonella Enterocolitis"

Transmission:

• Inadequately cooked poultry and eggs (common source) or meat

products.

• Contaminated food by excreta of animals e.g. rats.

• Human sources: patient during enterocolitis attack or chronic carriers.

Salmonella Food Poisoning "Salmonella Enterocolitis"
Pathogenesis:
• Invasion of the small and large intestines.

• Resulting in inflammation and diarrhea.

• Neutrophils limit the infection to the gut and the adjacent mesenteric
lymph nodes; bacteremia is infrequent in enterocolitis.
Salmonella Bacteremia with Focal Lesions
• Transient or persistent bacteremia.

• Mode of transmission of focal lesions: by Blood

• Bacteremia with localized foci resulting in persistent infection of many

organs with osteomyelitis, pneumonia, and meningitis as the most
common sequelae.
 SHIGELLA
Important properties:

• Gram-negative rods, Non-motile, Non-capsulate& Facultative anaerobe.

• Shigella is a true human pathogen, for which there is no animal
reservoir.
 SHIGELLA
Classification:

• The genus Shigella has 4 species or subgroups (A, B, C, and D) & several
serotypes.
• Subgroups and serotypes are differentiated from each other by their
biochemical characteristics and antigenic properties.
• 1. Group A = Shigella (Sh.) dysenteriae
• 2. Group B (Sh. flexneri)
• 3. Group C (Sh. boydii)
• 4. Group D (Sh. sonnei)
 SHIGELLA
Virulence:

1. Attachment & penetration of mucosal epithelial cells of large

intestine.

2. Intracellular spread proteins: facilitate transfer of bacteria to adjacent

cells.

3. Shiga Toxin:
 Pathogenesis:
Infection is limited tointestinal tract.
Epithelial cell M cell

Macrophages shigella

The bacteria enter epithelial cells

Shigella pass through M cells to from their basolateral aspect by
reach the submucosa. Macrophages endocytosis.
take up the bacilli, die and release the
bacteria.
The endocytotic vacuoles lyse
releasing the bacteria into the
cytoplasm.

The bacteria move intracellularly and

spread to adjacent cells.

Infected cells die leading to an acute

inflammatory response with migration of neutrophils to the
epithelial side
 SHIGELLA
Virulence:
Shiga Toxin:

1. It is produced by Shigella dysenteriae type 1.

2. It has the following characters:
3. Enterotoxic, neurotoxic and cytotoxic activity.
4. Encoded by chromosomal genes.
5. Similar to the Shiga-like toxin of enterohemorrhagic E. coli (EHEC)
0157:H7 strain except that Shiga-like toxin is encoded by lysogenic
bacteriophage.
 SHIGELLA
Virulence:
Shiga toxin cytotoxic activity:
Damage to epithelial cells of intestine:
 Inhibit protein synthesis, causing cell death
 vascular damage to the intestine, and hemorrhage (blood and fecal
leukocytes in stool).

• Damage to glomerular endothelial cells, leading to haemolytic uremic

syndrome (HUS).
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