Transcript E. coli

Enterobacteriaceae
Microbiology Department KUMS
Dr. Mohajeri
1


a large, heterogeneous group of G-ve rods
natural habitat is the intestinal tract of humans
and animals
 facultative anaerobes or aerobes
 ferment a wide range of carbohydrates (Glc+)
 possess a complex antigenic structure
 produce a variety of toxins and other virulence
factors
 catalase-positive, oxidase-negative
 reduce nitrate to nitrite
 The family includes many genera:
- Escherichia
- Shigella
- Salmonella
- Enterobacter
- Klebsiella
- Serratia
- Proteus and others
2

Some enteric organisms, eg, E.coli, are part of the
normal flora and incidentally cause disease, while
others, the salmonellae and shigellae, are regularly
pathogenic for humans.

coliforms:
- Escherichia
- Enterobacter
- Klebsiella
- Citrobacter
3
Classification

along with staphylococci and streptococci are
among the most common bacteria that cause
disease

More than 25 genera and 110 species
4
5
Tribe I:
Escherichia →
Escherichia
Shigella
Tribe II: Edwardsielleae → Edwardsielleae
Tribe III: Salmonelleae → Salmonella
Tribe IV: Citrobacter →
Citrobacter
Tribe V: Klebsielleae →
Klebsiella
Enterobacter
Hafnia
Pantoea
Serratia
Tribe VI: Proteae →
Proteus
Morganella
Providencia
Tribe VII: Yersinieae → Yersinia
Antigenic Structure

have a complex antigenic structure:
- >150 different heat-stable somatic O (LPS
antigens
- >100 heat-labile K (capsular) antigens
- > 50 H (flagellar) antigens

In S. typhi, the capsular antigens are called Vi
antigens.
8
9
O antigens

cell wall LPS and consist of repeating units of
polysaccharide
 are resistant to heat and alcohol
 usually are detected by bacterial agglutination
 Antibodies to O antigens are predominantly IgM
 While each genus of Enterobacteriaceae is
associated with specific O groups, a single
organism may carry several O antigens.

Thus, most shigellae share one or more O
antigens with E. coli.
 E. coli may cross-react with some Providencia,
Klebsiella and Salmonella species.
10
K antigens


are external antigen but not all Enterobacteriaceae
Some are polysaccharides, including the K
antigens of E. coli; others are proteins

K antigens may interfere with agglutination by O
antisera, and they may be associated with virulence
(eg, E. coli strains producing K1 antigen are
prominent in neonatal meningitis, and K antigens
of E. coli cause attachment of the bacteria to
epithelial cells prior to gastrointestinal or urinary tract
invasion).
11

Klebsiellae form large capsules consisting of
polysaccharides (K antigens) covering the somatic
(O or H) antigens and can be identified by capsular
swelling tests with specific antisera.
- capsular types 1 and 2
→ human respiratory tract infections
- types 8, 9, 10 and 24
→ UTI
12
H antigens

are located on flagella and are denatured or
removed by heat or alcohol
 They are preserved by treating motile bacterial
variants with formalin
 Such H antigens agglutinate with anti-H antibodies,
mainly IgG


Subunite name: flagellin
Within a single serotype, flagellar antigens may be
present in either or both of two forms, called phase 1
(conventionally designated by lower-case letters) and
phase 2 (conventionally designated by Arabic
numerals)
13
14

The organism tends to change from one phase to
the other; this is called phase variation
 H antigens on the bacterial surface may interfere
with agglutination by anti-O antibody.
 There are many examples of overlapping
antigenic structures between Enterobacteriaceae
and other bacteria:
- Most Enterobacteriaceae share the O14
antigen of E. coli
- The type 2 capsular polysaccharide of
klebsiellae is very similar to the
polysaccharide of type 2 pneumococci
- Some K antigens cross-react with capsular
polysaccharides of H.influenzae or N.
meningitidis
- Thus, E. coli O75:K100:H5 can induce
antibodies that react with H. influenzae type b.
15

antigenic formula:
- E. coli O55:K5:H21
- Salmonella schottmülleri O1,4,5,12:Hb:1,2
Colicins (Bacteriocins)


Many G-ve organisms produce bacteriocins
These virus-like bactericidal substances are
produced by certain strains of bacteria active
against some other strains of the same or closely
related species
 Their production is controlled by plasmids.
16

e.g:
- Colicins by E. coli
- Marcescens by serratia
- Pyocins by pseudomonas
 Bacteriocin-producing strains are resistant to their
own bacteriocin; thus, bacteriocins can be used for
"typing" of organisms.
Toxins & Enzymes
 LPS (endotoxins), have a variety of
pathophysiologic effects
 Many G-ve enteric bacteria also produce
exotoxins of clinical importance.
17
18
Diseases Caused by Enterobacteriaceae
Other Than Salmonella & Shigella
Causative Organisms
 E. coli is a member of the normal intestinal flora.
 Proteus, Enterobacter, Klebsiella, Morganella,
Providencia, Citrobacter and Serratia are also
found as members of the normal intestinal flora but
are considerably less common than E. coli
 The enteric bacteria generally do not cause
disease.
 hospital-acquired infections and occasionally
cause community-acquired infections
 The bacteria become pathogenic only when they
reach tissues outside of their normal intestinal or
other less common normal flora sites.
19
 The most frequent sites of clinically important
infection are:
- the urinary tract
- biliary tract
- other sites in the abdominal cavity
but any anatomic site (eg, bacteremia, prostate
gland, lung, bone, meninges) can be the site of
disease.
 Some of the enteric bacteria (eg, Serratia
marcescens, Enterobacter aerogenes) are
opportunistic pathogens.
Pathogenesis & Clinical Findings
 depend on the site of the infection
20
E. coli
Urinary Tract Infection (UTI)
 E. coli is the most common cause of UTI (90% of
first UTIs in young women)
 The symptoms and signs include urinary
frequency, dysuria, hematuria and pyuria. Flank pain
is associated with upper tract infection.
 UTI can result in bacteremia with clinical signs of
sepsis.
 Nephro (Uro) pathogenic E. coli typically
produce a hemolysin.
 Most of the infections are caused by E. coli of a
small number of O antigen types.
21
 K antigen appears to be important in the
pathogenesis of UTI.
 Pyelonephritis is associated with a specific type
of pilus, P pilus, which binds to the P blood group
substance.
E. coli - Associated Diarrheal Diseases
 are classified by the characteristics of their
virulence properties
 each group causes disease by a different
mechanism
 The small or large bowel epithelial cell adherence
properties are encoded by genes on plasmids
 The toxins often are plasmid- or phage-mediated.
22
E. coli virutypes
Enteropathogenic E. coli (EPEC)
 is an important cause of diarrhea in infants,
especially in developing countries
 adhere to the mucosal cells of the small bowel
 Chromosomally mediated factors promote tight
adherence
 There is loss of microvilli (effacement), formation
of filamentous actin pedestals or cup-like
structures and, occasionally, entry of the EPEC
into the mucosal cells.
 The result of EPEC infection is watery
diarrhea, which is usually self-limited but can be
chronic
 EPEC diarrhea has been associated with multiple
specific serotypes of E. coli
23
Enterotoxigenic E. coli (ETEC)
 is a common cause of "traveler's diarrhea“
 cause of a very important cause of diarrhea in
infants
 ETEC adhere to epithelial cells of the small bowel
 Some strains of ETEC produce a heat-labile
exotoxin (LT) that is under the genetic control of a
plasmid:
→ its subunit B attaches to the GM1
ganglioside at the brush border of epithelial
cells of the small intestine
→ facilitates the entry of subunit A into the
cell
24
→ activates adenylyl cyclase
→ increases the local concentration of cAMP
→ intense and prolonged hypersecretion
of water and chlorides
→ inhibits the reabsorption of Na+
→ diarrhea for several days
 LT is antigenic and cross-reacts with the
enterotoxin of V. cholerae
25
Assays for LT detection:
1) fluid accumulation in the intestine of laboratory
animals
2) typical cytologic changes in cultured Chinese
hamster ovary cells or other cell lines
3) stimulation of steroid production in cultured
adrenal tumor cells
4) binding and immunologic assays with
standardized antisera to LT
26
 Some strains of ETEC produce the heat-stable
enterotoxin Sta, which is under the genetic control
of a heterogeneous group of plasmids.
 STa activates guanylyl cyclase in enteric
epithelial cells
→ stimulates fluid secretion
 Many STa - positive strains also produce LT
 The strains with both toxins produce a more
severe diarrhea
 The plasmids carrying the genes for enterotoxins
(LT, ST) also may carry genes for the colonization
factors that facilitate the attachment to intestinal
epithelium
27
Enterohemorrhagic E. coli (EHEC)
 produces verotoxin: named for its cytotoxic
effect on Vero cells (a line of African green monkey
kidney cells)
 There are at least two antigenic forms of the toxin
 EHEC has been associated with:
- hemorrhagic colitis (HC),
a severe form of diarrhea
- hemolytic uremic syndrome (HUS),
a disease resulting in acute renal failure
 Verotoxin are similar to the Shiga toxin produced
by Shigella dysenteriae type 1
 cooking ground beef
28
 E. coli O157:H7 is the most common
- does not use sorbitol, unlike most other E. coli
- is negative on sorbitol MacConkey agar (sMAC)
- are negative on MUG tests
- Specific antisera are used to identify
Enteroinvasive E. coli (EIEC)
 produces a disease very similar to shigellosis
 occurs most commonly in children in developing
countries and in travelers to these countries
 Like shigella, EIEC strains are nonlactose or late
lactose fermenters and are nonmotile
 produce disease by invading intestinal mucosal
epithelial cells
29
Enteroaggregative E. coli (EAEC)
 causes acute and chronic diarrhea (> 14 days in
duration)
 cause of food-borne disease (FBD) in
industrialized countries
 Characterization: pattern of adherence to human
cells
 produce ST-like toxin and a hemolysin
30
Sepsis

When normal host defenses are inadequate, E.
coli may reach the bloodstream and cause sepsis
 Newborns may be highly susceptible to E. coli
sepsis because they lack IgM antibodies
 Sepsis may occur secondary to UTI
Meningitis
 E. coli and group B streptococci are the leading
causes of meningitis in infants
 Approximately 75% of E. coli from meningitis
cases have the K1 antigen
 This antigen cross-reacts with the group B
capsular polysaccharide of N. meningitidis
31
Klebsiella
 K. pneumoniae is present in the respiratory tract
and feces of about 5% of normal individuals
 causes 1% of bacterial pneumonias
 can produce extensive hemorrhagic necrotizing
consolidation of the lung
 occasionally produces UTI and bacteremia with
focal lesions in debilitated patients
 K. pneumoniae, K.oxytoca
→ cause hospital-acquired infections
 K. ozaenae
→ causes ozena
 K. rhinoscleromatis
→ causes rhinoscleroma
32
Enterobacter aerogenes
 has small capsules
 free-living as well as in the intestinal tract
 causes UTI and sepsis
Serratia
o S. marcescens is a common opportunistic
pathogen in hospitalized patients
o Serratia (usually nonpigmented) causes
pneumonia, bacteremia and endocarditis-especially
in narcotics addicts and hospitalized patients
o Only about 10% of isolates form the red pigment
(prodigiosin) that has long characterized Serratia
marcescens
33
Proteus
 produce infections in humans only when the
bacteria leave the intestinal tract
 Produce UTI, bacteremia, pneumonia and focal
lesions in debilitated patients or those receiving
intravenous infusions
 P. mirabilis causes UTI and occasionally other
infections.
 P. vulgaris and Morganella morganii are
important nosocomial pathogens.
34
 Proteus species produce urease, resulting in
rapid hydrolysis of urea with liberation of ammonia
 Thus, in UTI with proteus, the urine becomes
alkaline, promoting stone formation
 The rapid motility of proteus may contribute to its
invasion of the urinary tract
 Strains of proteus vary greatly in antibiotic
sensitivity
35
Providencia
 Providencia species (P. rettgeri, P. alcalifaciens,
and P. Stuartii ) are members of the normal
intestinal flora
 All cause UTI and occasionally other infections
and are often resistant to antimicrobial therapy.
Citrobacter
cause UTI and sepsis
36
Diagnostic Laboratory Tests
Specimens
 Specimens included urine, blood, pus, spinal
fluid, sputum
Culture
 Specimens are plated on both blood agar and
differential media. With differential media, rapid
preliminary identification of G-ve bacteria is often
possible.
37
Treatment
 sulfonamides, ampicillin, cephalosporins,
fluoroquinolones and aminoglycosides
 Multiple drug resistance is common and is under
the control of transmissible plasmids.
Epidemiology, Prevention & Control
 The enteric bacteria establish themselves in the
normal intestinal tract within a few days after birth.
 Enterics found in water or milk are accepted as
proof of fecal contamination from sewage or other
sources.
38

E. coli serotypes should be controlled like
salmonellae.
 many enteric bacteria are "opportunists" that
cause illness in debilitated patients
39
The Shigellae

The natural habitat of shigellae is limited to the
intestinal tracts of humans and other primates,
where they produce bacillary dysentery.
 With the exception of Shigella sonnei, they do
not ferment lactose
40
Antigenic Structure
 The somatic O antigens are more than 40
serotypes.
Pathogenesis & Pathology
 Shigella infections are almost always limited to
the gastrointestinal tract.

bloodstream invasion is quite rare.
Shigellae are highly communicable; the infective
dose (ID) is on the order of 103 organisms (whereas
it usually is 105–108 for salmonellae and vibrios)

41

The essential pathologic process:
- invasion of the mucosal epithelial cells (eg,
M cells) by induced phagocytosis
- escape from the phagocytic vacuole
- multiplication and spread within the epithelial
cell cytoplasm
- passage to adjacent cells
- Microabscesses in large intestine and
terminal ileum → necrosis of the mucous
membrane, superficial ulceration, bleeding,
and formation of a "pseudomembrane" on the
ulcerated area.
42
Toxins
- Endotoxin
 all shigellae release their toxic LPS (endotoxin)
- Shigella dysenteriae Exotoxin
 S. dysenteriae type 1 (Shiga bacillus) produces a
heat-labile exotoxin that affects both the gut and the
central nervous system (CNS).
 Acting as an enterotoxin, it produces diarrhea as
does the E. coli verotoxin, perhaps by the same
mechanism.
 In humans, the exotoxin also inhibits sugar and
amino acid absorption in the small intestine. Acting
as a "neurotoxin"
43
Patients with S. flexneri or S. sonnei infections
develop antitoxin that neutralizes S. dysenteriae
exotoxin in vitro.

Clinical Findings
 The illness due to S. dysenteriae may be
particularly severe.
Diagnostic Laboratory Tests
 Specimens include fresh stool, mucus flecks and
rectal swabs for culture.
 salmonella-shigella (SS) agar → suppress other
Enterobacteriaceae and G+ve organisms
 are nonmotile
44
Immunity
 IgA antibodies in the gut may be important in
limiting reinfection; these may be stimulated by live
attenuated strains given orally as experimental
vaccines.
 Serum antibodies to somatic shigella antigens are
IgM.
Treatment
 Ciprofloxacin, ampicillin, doxycycline and
trimethoprim-sulfamethoxazole (SXT)
 Multiple drug resistance can be transmitted by
plasmids
 Many cases are self-limited
45
Epidemiology, Prevention & Control
 4F: Shigellae are transmitted by "food, fingers,
feces and flies" from person to person.
Most cases of shigella infection occur in children
under 10 years of age.


control efforts:
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,
particularly food handlers
4) antibiotic treatment of infected individuals
46
The Salmonella-Arizona Group
 Salmonellae are often pathogenic for humans or
animals when acquired by the oral route
 cause enteritis, systemic infection and enteric
fever
 Most isolates are motile with peritrichous flagella
 They usually produce H2S
 They survive freezing in water for long periods
 Salmonellae are resistant to certain chemicals
(eg, brilliant green, sodium tetrathionate, sodium
deoxycholate) that inhibit other enteric bacteria
 The classification of salmonellae is complex.
47
 The members of the genus Salmonella were
originally classified on the basis of epidemiology,
host range, biochemical reactions and structures of
the O, H and Vi (when present) antigens.
 DNA-DNA hybridization studies:
- seven groups
** Nearly all of the salmonella serotypes that infect
humans are in DNA hybridization group I
there are rare human infections with groups IIIa and
IIIb.
48
e.g:
S. enterica subspecies enterica serotype
Typhimurium = can be shortened to S. typhimurium
 There are >2500 serotypes of salmonellae,
including >1400 in DNA hybridization group I that
can infect humans.
49
 Four serotypes of salmonellae that cause enteric
fever can be identified in the clinical laboratory by
biochemical and serologic tests.
 These serotypes should be routinely identified
because of their clinical significance.
 They are as follows:
- Salmonella Paratyphi A
- Salmonella Paratyphi B
- Salmonella Choleraesuis
- Salmonella typhi
(serogroup A)
(serogroup B)
(serogroup C1)
(serogroup D)
50
 The more than 1400 other salmonellae that are
isolated in clinical laboratories are serogrouped by
their O antigens as A, B, C1, C2, D and E
 Variation:
- Organisms may lose H antigens and become
nonmotile.
- Loss of O antigen is associated with a change
from smooth to rough colony form.
- Vi antigen may be lost partially or completely.
51
Pathogenesis & Clinical Findings
 Salmonella typhi, Salmonella Choleraesuis and
perhaps Salmonella Paratyphi A and Salmonella
Paratyphi B are primarily infective for humans
(human source)
 The vast majority of salmonellae, however, are
chiefly pathogenic in animals that constitute the
reservoir for human infection: poultry, pigs,
rodents, cattle, pets (from turtles to parrots) and
many others.
 The organisms almost always enter via the oral
route, usually with contaminated food or drink.
52
The mean infective dose to produce clinical or
subclinical infection in humans is 105–108
salmonellae (but perhaps as few as 103 Salmonella
typhi organisms)

Among the host factors that contribute to
resistance to salmonella infection are gastric acidity,
normal intestinal microbial flora and local intestinal
immunity.

53
Salmonellae produce three main types of disease
in humans, but mixed forms are frequent:
54
The "Enteric Fevers" (Typhoid Fever)
 This syndrome is produced by only a few of the
salmonellae, of which Salmonella typhi (typhoid
fever) is the most important.
 The ingested salmonellae:
→ reach the small intestine
→ enter the lymphatics
→ enter the bloodstream
→ carried by the blood to many organs,
including the intestine
→ multiply in intestinal lymphoid tissue
→ are excreted in stools
55
 mortality rate was 10–15%
 Treatment with antibiotics has reduced the
mortality rate to less than 1%.
 The principal lesions are hyperplasia and
necrosis of lymphoid tissue (eg, Peyer's patches),
hepatitis, focal necrosis of the liver and inflammation
of the gallbladder, periosteum, lungs and other
organs.
56
Bacteremia with Focal Lesions
 This is associated commonly with S. choleraesuis
but may be caused by any salmonella serotype.
Following oral infection, there is early invasion of
the bloodstream (with possible focal lesions in
lungs, bones, meninges, etc) but intestinal
manifestations are often absent.


Blood cultures are positive.
57
Enterocolitis
 This is the most common manifestation of
salmonella infection.
 In the United States, Salmonella typhimurium
and Salmonella enteritidis are prominent, but
enterocolitis can be caused by any of the more than
1400 group I serotypes of salmonellae.
 Bacteremia is rare (2–4%) except in
immunodeficient persons.
 Blood cultures are usually negative, but stool
cultures are positive for salmonellae and may
remain positive for several weeks after clinical
recovery.
58
Diagnostic Laboratory Tests
 Blood for culture must be taken repeatedly.
 In enteric fevers and septicemias, blood cultures
are often positive in the first week of the disease.
 Bone marrow cultures may be useful.
 Urine cultures may be positive after the second
week.
 Stool specimens also must be taken repeatedly.
 A positive culture of duodenal drainage
establishes the presence of salmonellae in the
biliary tract in carriers.
59
Bacteriologic Methods for Isolation of
Salmonellae
 Many salmonellae produce H2S
 Selective Medium Cultures:
- salmonella-shigella (SS) agar
 The specimen (usually stool) also is put into
selenite F or tetrathionate broth, both of which
inhibit replication of normal intestinal bacteria and
permit multiplication of salmonellae.
 After incubation for 1–2 days, this is plated on
differential and selective media.
 biochemical reaction patterns
 There are commercial kits available to agglutinate
and serogroup salmonellae by their O antigens: A,
B, C1, C2, D and E.
60
Serologic Methods
 Tube Dilution Agglutination Test (Widal Test)
 Serum agglutinins rise sharply during the second
and third weeks of Salmonella typhi infection.
 The Widal test to detect these antibodies against
the O and H antigens has been in use for decades.
 The interpretive criteria when single serum
specimens are tested vary, but a titer against the O
antigen of >1:320 and against the H antigen of
>1:640 is considered positive.
 High titer of antibody to the Vi antigen occurs in
some carriers.
 The test is not useful in diagnosis of enteric
fevers caused by salmonella other than S. typhi.
61
Treatment
 Antimicrobial therapy of invasive salmonella
infections is with ampicillin, SXT or a thirdgeneration cephalosporin.
Multiple drug resistance transmitted genetically by
plasmids among enteric bacteria is a problem in
salmonella infections.

In most carriers, the organisms persist in the
gallbladder (particularly if gallstones are present)
and in the biliary tract.

62
Epidemiology
 carriers working as food handlers are "shedding"
organisms
 Many animals, including cattle, rodents, and fowl,
are naturally infected with a variety of salmonellae
and have the bacteria in their tissues (meat),
excreta or eggs
 The high incidence of salmonellae in
commercially prepared chickens has been widely
publicized.
63
Carriers
3% of survivors of typhoid become permanent
carriers.
 harboring the organisms in the gallbladder, biliary
tract, or, rarely, the intestine or urinary tract.

Sources of Infection
 Water
 Milk and Other Dairy Products (Ice Cream,
Cheese, Custard)
 Shellfish
 Eggs
 Meats and Meat Products
 From infected animals (poultry) or contamination
with feces by rodents or humans.
64
Marijuana and other drugs
Animal Dyes: eg, carmine, used in drugs, foods,
and cosmetics.
 Household Pets
 Turtles, dogs, cats, etc.


Prevention & Control
 Infected poultry, meats, and eggs must be
thoroughly cooked.
 Carriers must not be allowed to work as food
handlers and should observe strict hygienic
precautions.
65
66
Yersinieae
 pleomorphic G-ve rods, bipolar staining,
catalase-positive, oxidase-negative and
microaerophilic or facultatively anaerobic
 Most have animals as their natural hosts, but they
can produce serious disease in humans.
 The genus Yersinia includes:
- Y. pestis → plague
- Y. pseudotuberculosis and
Yersinia enterocolitica → important causes
of human diarrheal diseases
67
Yersinia pestis & Plague
Plague is an infection of wild rodents, transmitted
from one rodent to another and occasionally from
rodents to humans by the bites of fleas.

Serious infection often results, which in previous
centuries produced pandemics of "black death"
with millions of fatalities.

Morphology & Identification
 G-ve rod with bipolar staining ends, nonmotile
 Growth is more rapid in media containing blood or
tissue fluids and fastest at 30 °C
 In cultures on blood agar at 37 °C, colonies may
be very small at 24 hours
68
A virulent inoculum, derived from infected tissue,
produces gray and viscous colonies, but after
passage in the laboratory the colonies become
irregular and rough.

The organism has little biochemical activity and
this is somewhat variable.

69
Yersinia pestis (arrows) in blood
70
Antigenic Structure
 All yersiniae possess LPS that have endotoxic
activity when released.
The three pathogenic species produce antigens
and toxins that act as virulence factors.

They have type III secretion systems that consist
of a membrane-spanning complex that allows the
bacteria to inject proteins directly into cytoplasm of
the host cells.

71
The virulent yersiniae produce V and W
antigens, which are encoded by genes on a
plasmid of approximately 70 kb.


This is essential for virulence
the V and W antigens yield the requirement for
calcium for growth at 37 °C.

In Y. pestis there is a capsular protein (fraction
I) that is produced mainly at 37 °C and confers
antiphagocytic properties

the gene for this protein is on a plasmid of
approximately 110 kb.

72

Y. pestis has a 9.6-kb plasmid that yields a:
- plasminogen-activating protease
- temperature-dependent coagulase
activity (20-28 °C, the temperature of the flea)
- fibrinolytic activity (35-37 °C, the
temperature of the host).
The three pathogenic yersiniae have a
pathogenecity island (PAI) that encodes for an ironscavenging siderophore.

73
Among several exotoxins produced, one is lethal
for mice in amounts of 1 µg. This homogeneous
protein produces beta-adrenergic blockade and is
cardiotoxic in animals. Its role in human infection is
unknown.

74
Pathogenesis & Pathology
 When a flea feeds on a rodent infected with Y.
pestis
→ the ingested organisms multiply in the gut of the
flea (helped by the coagulase)
→ block its proventriculus so that no food can pass
through
→ Subsequently, the "blocked" and hungry flea bites
ferociously and the aspirated blood, contaminated
with Y. pestis from the flea
→ The inoculated organisms may be phagocytosed
by PMNs and monocytes.
75
→ The Y. pestis organisms are killed by the PMNs
but multiply in the monocytes; because the bacteria
are multiplying at 37 °C
→ They produce the antiphagocytic protein and
subsequently are able to resist phagocytosis
→ The pathogens rapidly reach the lymphatics and
an intense hemorrhagic inflammation develops in
the enlarged lymph nodes
→ Hemorrhagic and necrotic lesions may develop in
all organs; meningitis, pneumonia.
76
Primary pneumonic plague results from
inhalation of infective droplets (usually from a
coughing patient), with hemorrhagic consolidation,
sepsis, and death.

77
Clinical Findings
 2–7 days incubation period
→ high fever
→ painful lymphadenopathy
→ greatly enlarged, tender nodes ("buboes")
in the groin or axillae
→ Vomiting and diarrhea may develop with
early sepsis
→ disseminated intravascular coagulation
(DIC)
→ hypotension, altered mental status, and
renal and cardiac failure
→ pneumonia and meningitis
→ Y. pestis multiplies intravascularly and can
be seen in blood smears.
78
Diagnostic Laboratory Tests
Blood is taken for culture and aspirates of
enlarged lymph nodes for smear and culture.
 In pneumonia, sputum is cultured
 in possible meningitis, CSF is taken for smear
and culture.

Smears
 Spinal fluid and sputum smears should also be
stained. (Wayson's stain)
79
Culture
 All materials are cultured on blood agar and
MacConkey's agar plates and in infusion broth.
 All cultures are highly infectious and must be
handled with extreme caution.
Treatment
 Unless promptly treated, plague may have a
mortality rate of nearly 50%; pneumonic plague,
nearly 100%.
 The drug of choice is streptomycin. Tetracycline is
an alternative drug.
 Drug resistance has been noted in Y. pestis.
80
Epidemiology & Control
 Plague is an infection of wild rodents (field mice,
gerbils, moles, skunks and other animals) that
occurs in many parts of the world.
 enzootic areas: India, Southeast Asia (especially
Vietnam), Africa, North and South America
 The commonest vector of plague is the rat flea
(Xenopsylla cheopis), but other fleas may also
transmit the infection.
 The control of plague requires surveys of infected
animals, vectors and human contacts
 All patients with suspected plague should be
isolated
81
Contacts of patients with suspected plague
pneumonia should receive tetracycline, as
chemoprophylaxis.
 A formalin-killed vaccine is available for travelers
to hyperendemic areas and for persons at special
high risk

82
Y. enterocolitica & Y. pseudotuberculosis
Lac-, G-ve rods, urease+, and oxidasegrow best at 25 °C and are motile at 25 °C but
nonmotile at 37 °C
 They are found in the intestinal tract of a variety
of animals, in which they may cause disease and
are transmissible to humans
 > 50 serotypes
 most isolates from human disease: O3, O8, O9
 There are striking geographic differences in the
distribution of serotypes.
 Y. enterocolitica can produce a heat-stable
enterotoxin.


83
Y. enterocolitica has been isolated from rodents
and domestic animals (eg, sheep, cattle, swine,
dogs and cats) and waters contaminated by them.

Transmission to humans probably occurs by
contamination of food, drink or fomites.

84
Y. pseudotuberculosis exists in at least six
serotypes, but serotype O1 accounts for most
human infections.

Y. pseudotuberculosis occurs in domestic and
farm animals and birds, which excrete the
organisms in feces.

Human infection probably results from ingestion
of materials contaminated with animal feces.

Person-to-person transmission with either of
these organisms is probably rare.

85
Pathogenesis & Clinical Findings
 An inoculum of 108–109 yersiniae must enter the
alimentary tract to produce infection.
 During the incubation period of 5–10 days,
yersiniae multiply in the gut mucosa, particularly the
ileum.
 The process may extend to mesenteric lymph
nodes and, rarely, to bacteremia.
 Early symptoms include fever, abdominal pain,
and diarrhea (from watery to bloody)
 develop arthralgia, arthritis and erythema
nodosum, suggesting an immunologic reaction to
the infection.
86
Very rarely, yersinia infection produces
pneumonia, meningitis or sepsis; in most cases, it is
self-limited.

Diagnostic Laboratory Tests
 Specimens may be stool, blood or material
obtained at surgical exploration.
 The number of yersiniae in stool may be small
and can be increased by "cold enrichment":
- a small amount of feces or a rectal swab is placed
in buffered saline, pH 7.6, and kept at 4 °C for 2–4
weeks; many fecal organisms do not survive, but Y
enterocolitica will multiply. Subcultures made at
intervals on MacConkey agar may yield yersiniae.
87
Treatment
 Most yersinia infections with diarrhea are selflimited
 Y. enterocolitica is generally susceptible to
aminoglycosides, chloramphenicol, tetracycline,
SXT, piperacillin, third-generation cephalosporins,
and fluoroquinolones.
Prevention & Control
 Contact with farm and domestic animals, their
feces or materials contaminated by them probably
accounts for most human infections.
 Meat and dairy products have occasionally been
indicated as sources of infection
88
89
90