BACTERIAL
PATHOGENS
OF
HUMANS
INTRODUCTION
Medically important bacteria may be
classified into five main groups that
include gram-positive, gram-negative,
acid fast, spiral and cell wall deficient
bacteria.
Note:
1. Morphology, Growth characteristics,
Virulence (pathogens' invasiveness,
intoxication
and
1
hypersensitivity
owing to genetic or biochemical or
structural features), infective dosages,
Pathogenicity (the ability of bacteria
to
cause
disease
colonization
characteristics
in
a
and
relating
host),
disease
to
each
organism discussed.
2. Also note the overlapping causative
agents of typical infectious diseases
and
the
organs
or
body
parts
commonly affected.
3. The most common sites of microbial
entry are: (1) mucosal surfaces
2
comprising the respiratory, ear canal,
alimentary and genitourinary tracts;
(2) the skin or the conjunctiva in the
case of eye infections.
4. Aetiology of bacterial diseases is
compounded
by
the
need
to
differentiate between the the “good”
and the “bad” bacteria. Diseases such
as:
Bacterial
meningitis,
Urinary
vaginosis,
Bacterial
tract
Bacterial
pneumonia,
infection
(UTI),
Bacterial gastroenteritis, and Bacterial
skin infections (Impetigo, Erysipelas,
3
and
Cellulitis)
have
multiple
aetilogies. Also note that bacteria can
cause multiple aetilogies.
5. Avoidance of innate host defence
mechanisms including but not limited
to barriers such as mucous, secretions
(lysozyme,
interferons
e.t.c.),
complement
system,
acidity,
Phagocytic
and
inflammatory
responses.
Note: Complement is a set of proteins
circulating in the blood stream which,
4
on activation by the presence of
microbes
complexes
or
antibody-antigen
attract
phagocytes,
enhance phagocytic ability and form a
membrane attack complex which can
kill gram-negative bacteria.
GRAM POSITIVE AND NEGATIVE
COCCI
5
Pyogenic Cocci (various pus-producing
spherical bacteria)
Gram-positive cocci
Staphylococcus aureus, Streptococcus
pyogenes
and
Streptococcus
pneumoniae,
Gram-negative cocci
Neisseria
gonorrhoeae
meningitidis.
STAPHYLOCOCCUS
6
and
N.
Staphylococcus aureus, S. epidermidis
or S. albus and S. saprophyticus are
three clinically important members of
staphylococcus species.
S.aureus is the most
staphylococcal
virulent of
species
It
characteristically produces coagulase
enzyme which enables it to coagulate
plasma. S. saprophyticus is a pathogen
of the urinary tract.
Staphylococcus epidermidis lives on
the
skin
and
mucous
7
membranes
(normal flora). S. epidermidis is rarely a
pathogen and probably benefits its host
by producing acids on the skin that
retard the growth of dermatophytic
fungi.
Staphylococcus aureus occur normally
on mucous membranes. S. aureus cause:
Boils (pimples), wound infections,
pneumonia, osteomyelitis, septicemia,
food intoxication, and toxic shock
syndrome. S. aureus is the leading
cause of nosocomial infections by
8
Gram-positive bacteria. Also, it is
usually resistant to penicillin and many
other antibiotics.
Streptococcus and Enterococcus
Streptococci are gram-positive cocci
often seen growing in pairs or chains.
They
are
non-sporing
facultative
aerobes which may occasionally have
capsules. Enterococci, have similar
characteristics as streptococci and were
formerly classified as Streptococci.
Enterococci differ from Streptococci in
9
their ability to grow on bile salt
containing media.
Streptococci
can
be
described
as
haemolytic or non haemolytic. The
haemolytic streptococci may have α
(green colouration) or β haemolysis
(colourless) haemolysis.
Streptococci also have carbohydrate
antigens in their cell envelops that give
different reactions to antibodies in
agglutination tests, and provide a basis
for
classification
known
as the
Lancefield system of classification,
10
such as Lancefield Groups A, B, C, D
up to G.
Streptococcus
pyogenes
cause
suppurative diseases and toxinoses,
autoimmune or allergic diseases. S.
pyogenes is the main streptococcal
pathogen causes tonsillitis or strep
throat. Streptococci also invade the
skin to cause localized infections and
lesions, and produce toxins that cause
scarlet
fever
and
toxic
shock.
Sometimes, as a result of an acute
11
streptococcal
infection,
anomalous
immune responses are started that lead
to diseases like rheumatic fever and
glomerulonephritis, which are called
post-streptococcal
sequelae.
Streptococci are sensitive to penicillin
and the other beta lactam antibiotics.
Streptococcus pneumoniae is the most
frequent cause of bacterial pneumonia
in humans. It is also a frequent cause of
otitis media (infection of the middle
ear) and meningitis. The bacterium
12
colonizes the nasopharynx and from
there gains access to the lung or to the
eustachian tube. If the bacteria descend
into the lung they evade engulfment by
alveolar macrophages if they possess a
capsule which somehow prevents the
engulfment
process.
Encapsulated
strains are able to invade the lung and
noncapsulated strains, which are readily
removed
by
phagocytes,
nonvirulent.
13
are
Note that pneumonia may be caused by
various bacteria as shown in the Table
below
Organism Predisposing
factor
Symptoms
to
infection
Streptococ Older patients Sudden
cus
or
patients onset
pneumoni with various pleuritic
ae
underlying
diseases
prior
pain, fever,
or rusty
sputum, cold
14
hospitali-
sores;
or
sation of any Pneumonia
kind.
in
the
chronic
bronchitic
Staphyloc Long
term
occi
use
of
aureus
glucocorticoi
ds
or
pneumonia
following
influenza
15
Haemophi Acute
lus
or
chronic
influenzae inflammation
of the airways
i.e. chronic or
acute
bronchitis
Klebsiella Predisposing
Thick
pneumoni disease eg
viscous
ae
alcoholism,
purulent red
diabetics;
sputum,
hospitalisatio pneumothor
16
n, Mechanical ax on X-ray
ventilation
Moraxella Associated
catarrhali with
s
pneumonia in
older adults,
long
of
history
cigarette
smoking,
underlying
chronic
obstructive
17
pulmonary
disease
lung
or
cancer
and
malnutrition.
Mycoplas Associated
ma
with
Non
productive
pneumoni pneumonia in cough,
ae
older adults
pharyngitis
in
young
adult,
ambulant
18
despite
positive
chest X-ray
Legionella Being
a Non
pneumoph middle
ila
aged productive
male,
cough,
smoking,
confusion,
exposure
to diarrhoea,
air
conditioning
or
hotel
shower
19
Mycobacte Immunosuppr Upper lobe
rium
ession
consolidatio
tuberculos
n,
is
lymphadeno
pathy,
Chlamydi Associated
a
with
pneumoni pneumonia in
ae
older persons
Chlamydi Association
a psittaci
with birds
20
hilar
Group B streptococci (S. agalactiae)
are a frequent cause of peripartum
fever. The organisms easily colonise
infants delivered vaginally by mothers
are carriers of the bacteria. They are
major causes of neonatal sepsis and
meningitis. In neonatal sepsis the
neonate
patients
demonstrate
may
typically
respiratory
distress,
lethargy, and hypotension as symptoms.
21
Groups C and G streptococci cause
infections similar those of Group A.
These include pharyngitis, cellulitis and
soft
tissue
infections,
pneumonia,
bacteraemia, endocarditis and septic
arthritis
Group D streptococci (Enterococci)
E. faecalis and E. faecium, the most
significant pathogens of the enterococci
are more associated with infections in
patients who are elderly or debilitated,
patients in whom the balance of normal
22
flora has been altered by antibiotic
treatment or patients in whom the
mucosal or epithelial barrier has been
disrupted
for
example
by
catheterization. In these patients they
may be causative agents for urinary
tract
infections
and
nosocomial
bacteraemia. They are also frequent
causes of endocarditis, liver abscesses,
infectious complications of biliary
surgery, and diabetic foot ulcers
23
Anaerobic
streptococci
(Peptostreptococci)
Peptostreptococci
(P.
magnus,
P.
micros, P. asacharolyticus) are normal
commensals of mucosal surfaces of
mouth,
lower
gastrointestinal
and
female genital tract. They cause mixed
infections with these other anaerobic
organisms when a mucosal barrier of
the skin is compromised by surgery,
trauma,
tumour
and
necrosis.
24
ischemia
or
NEISSERIAE
The Neisseriae cause gonorrhea and
meningitis. Neisseriaceae is a family of
Gram-negative bacteria which are small
cocci usually seen in pairs. Most
neisseriae are normal flora or harmless
commensals of mammals living on
mucous membranes. In humans they are
common residents of the throat and
upper respiratory tract. Two species are
primary pathogens of man, Neisseria
gonorrhoeae
and
meningitidis.
25
Neisseria
Neisseria gonorrhoeae causes sexuallytransmitted
disease
and
may
be
asymptomatic such that an infected
mother can give birth and unknowingly
transmit the bacterium to the infant
during its passage through the birth
canal resulting in neonatal ophthalmia,
which may cause blindness. For this
reason an antimicrobial agent is usually
added to the newborn eye at the time of
birth.
26
Neisseria meningitidis is an important
cause
of
bacterial
meningitis,
an
inflammation of the meninges of the
brain and spinal cord. Other bacteria
that
cause
meningitis
Haemophilus
include
influenzae,
Staphylococcus aureus and Escherichia
coli. Meningococcal meningitis differs
from other causes in that it is often
responsible for epidemics of meningitis.
It occurs most often in children aged 6
to 11 months, but it also occurs in older
children and in adults.
27
LISTERIA MONOCYTOGENES
Listeria monocytogenes is a Grampositive rod-shaped bacterium. It is the
agent of listeriosis, a serious infection
caused by eating food contaminated
with the bacteria. The disease affects
primarily pregnant women, newborns,
and adults with weakened immune
systems.
The two main clinical manifestations
are sepsis and meningitis. Meningitis is
often complicated by encephalitis.
28
Microscopically, Listeria species appear
as small, Gram-positive rods, which are
sometimes arranged in short chains.
Flagella
are
produced
at
room
temperature but not at 37°C.
Pathogenesis
Listeria monocytogenes is presumably
ingested with raw, contaminated food.
An invasin secreted by the bacteria
enables the listeriae to penetrate host
cells of the epithelial lining if the
immune
system
is
29
compromised.
Listeria monocytogenes multiplies not
only
extracellularly
intracellularly,
after
but
within
also
macrophages
phagocytosis,
or
within
parenchymal cells which are entered by
induced phagocytosis.
The
bacteria
macrophages
first
and
appear
then
spread
in
to
hepatocytes in the liver. The bacteria
stimulate a CMI response that includes
the
production
interferon,
of
TNF,
macrophage
gamma
activating
factors and a cytotoxic T cell response.
30
Listeria are able to penetrate the
endothelial layer of the placenta and
thereby infect the fetus.
Haemophilus influenzae.
Haemophilus influenzae is a small, nonmotile
Gram-negative
Haemophilus
influenzae
bacteria.
requires
preformed growth factors that are
present in blood, specifically X factor
(i.e., hemin) and V factor (NAD or
NADP). In the laboratory, it is usually
31
grown on chocolate blood agar which is
prepared by adding blood to an agar
base at 80oC.
Pseudomonas aeruginosa.
P. aeruginosa strains produce two types
of soluble pigments, the fluorescent
pigment
pyoverdin
and
the
blue
pigment
pyocyanin.
The
latter
is
produced abundantly in media of lowiron content and functions in iron
metabolism in the bacterium. Pyocyanin
(from "pyocyaneus") refers to "blue
32
pus", which is a characteristic of
suppurative
infections
caused
by
Pseudomonas aeruginosa.
Resistance to Antibiotics
The bacterium is naturally resistant to
many antibiotics. It can create biofilms
which are impervious to therapeutic
concentrations
of
Pseudomonas
carries
antibiotics.
antibiotic
resistance plasmids.
Only a few antibiotics are effective
33
against
Pseudomonas
aeruginosa,
including fluoroquinolones, gentamycin
and imipenem. Cystic fibrosis patients
eventually
become
infected
with
Pseudomonas aeruginosa.
Bordetella pertussis and Whooping
Cough
B. pertussis produces a variety of
substances with toxic activity in the
class of exotoxins and endotoxins. It
produces the pertussis toxin which
mediates both the colonization and
34
toxemic stages of the disease. PTx is an
A-B exotoxin. The A subunit is an ADP
ribosyl transferase. The B component
binds to specific carbohydrates on cell
surfaces. PTx is transported from the
site of growth of the Bordetella to
various susceptible cells and tissues of
the host. Following binding of the B
component to host cells, the A subunit
is inserted through the membrane and
released into the cytoplasm. The A
subunit then transfers the ADP ribosyl
moiety of NAD to the membrane-bound
35
regulatory protein Gi that normally
inhibits adenylate cyclase resulting in
cough paroxysm.
Lipopolysaccharide:
Bordetella
pertussis possesses lipopolysaccharide
(endotoxin) in its outer membrane. The
lipopolysaccharide is alternative form of
Lipid A which is called Lipid X. Lipid
X causes activation of complement,
fever and hypotension. Lipid X, but not
Lipid A, is pyrogenic.
36
E. coli Diseases
Neonatal Meningitis
E. coli strains invade the blood stream
of infants from the nasopharynx or GI
tract and are carried to the meninges.
Intestinal Diseases Caused by E. coli
As a pathogen, E. coli is best known for
its ability to cause intestinal diseases.
Five classes (virotypes) of E. coli that
cause
diarrheal
diseases
37
are
now
recognized: enterotoxigenic E. coli
(ETEC),
enteroinvasive
E.
coli
(EIEC), enterohemorrhagic E. coli
(EHEC), enteropathogenic E. coli
(EPEC), and enteroaggregative E.
coli (EAEC). Each class falls within a
serological subgroup and manifests
distinct features in pathogenesis.
Enterotoxigenic E. coli (ETEC)
38
ETEC
may
produce
a
heat-labile
enterotoxin (LT) that is similar to
cholera toxin.
Enteroinvasive E. coli (EIEC)
EIEC closely resemble Shigella in their
pathogenic mechanisms and the kind of
clinical illness they produce.
Enteropathogenic E. coli (EPEC)
39
EPEC
induce
a
profuse
watery,
sometimes bloody, diarrhea.
Enteroaggregative E. coli (EAEC)
The distinguishing feature of EAEC
strains is their ability to attach to tissue
culture cells in an aggregative manner.
These
strains
are
associated
with
persistent diarrhea in young children.
They resemble ETEC strains in that the
bacteria adhere to the intestinal mucosa
40
and cause non-bloody diarrhea without
invading or causing inflammation.
Enterohemorrhagic E. coli (EHEC)
EHEC are recognized as the primary
cause of hemorrhagic colitis (HC) or
bloody diarrhea, which can progress to
the potentially fatal hemolytic uremic
syndrome (HUS.
There are many serotypes of this E. coli
strain but only those that have been
41
clinically
associated
designated
as
with
EHEC.
HC are
Of
these,
O157:H7 is the prototypic EHEC and
most
often
implicated
in
illness
worldwide. EHEC infections are mostly
food or water borne and have implicated
undercooked ground beef, raw milk,
cold sandwiches, water, unpasteurized
apple juice and vegetables
Vibrio cholerae
42
Cholera is a severe diarrheal disease.
Transmission to humans is by water or
food.
The clinical description of cholera
begins with sudden onset of massive
diarrhea. The patient may lose gallons
of protein-free fluid and associated
electrolytes,
bicarbonates
and
ions
within a day or two. This results from
the activity of the cholera enterotoxin
which activates the adenylate cyclase
enzyme
in
the
intestinal
cells,
converting them into pumps which
43
extract water and electrolytes from
blood and tissues and pump it into the
lumen of the intestine. This loss of fluid
leads to dehydration, anuria, acidosis
and shock. The watery diarrhea is
speckled with flakes of mucus and
epithelial cells ("rice-water ") and
contains enormous numbers of vibrios.
The loss of potassium ions may result in
cardiac complications and circulatory
failure. Untreated cholera frequently
results in high mortality rates.
44
Treatment of cholera involves the
rapid intravenous replacement of the
lost fluid and ions. Following this
replacement, administration of isotonic
maintenance solution should continue
until the diarrhea ceases. If glucose is
added to the maintenance solution it
may be administered orally, thereby
eliminating the need for sterility and iv.
administration. By this simple treatment
regimen, patients on the brink of death
seem to be miraculously cured and the
45
mortality rate of cholera can be reduced
more than ten-fold.
Cholera Toxin
Cholera toxin activates the adenylate
cyclase enzyme in cells of the intestinal
mucosa leading to increased levels of
intracellular cAMP, and the secretion of
H20, Na+, K+, Cl-, and HCO3- into the
lumen of the small intestine.
The net effect of the toxin is to cause
cAMP to be produced at an abnormally
high rate which stimulates mucosal cells
46
to pump large amounts of Cl- into the
intestinal contents. H2O, Na+ and other
electrolytes follow due to the osmotic
and electrical gradients caused by the
loss
of
Cl-.
electrolytes
in
The
lost
H 2O
and
mucosal
cells
are
replaced from the blood. Thus, the
toxin-damaged cells become pumps for
water and electrolytes causing the
diarrhea,
loss of
electrolytes, and
dehydration that are characteristic of
cholera.
47
Salmonella and Salmonellosis
Salmonella are the cause of two
diseases
called
salmonellosis,
and
enteric fever (typhoid), resulting from
bacterial invasion of the bloodstream,
and acute gastroenteritis, resulting
from a foodborne infection/intoxication.
Antigenic Structure
Somatic (O) or Cell Wall Antigens
Surface (Envelope) Antigens
48
Flagellar (H) Antigens
Shigella and Shigellosis
Shigellae
are
Gram-negative,
nonmotile, non-spore forming, rodshaped bacteria, very closely related to
Escherichia coli.
Shigellosis
Shigellosis is an infectious disease
caused by various species of Shigella.
People infected with Shigella develop
diarrhea, fever and stomach cramps
49
starting a day or two after they are
exposed to the bacterium. The diarrhea
is often bloody. Shigellosis usually
resolves in 5 to 7 days, but in some
persons, especially young children and
the elderly, the diarrhea can be so
severe that the patient needs to be
hospitalized.
Reiter's syndrome
Persons with diarrhea usually recover
completely, although it may be several
months before their bowel habits are
50
entirely normal. About 3% of persons
who are infected with Shigella flexneri
may subsequently develop pains in their
joints, irritation of the eyes, and painful
urination. This condition is called
Reiter's syndrome.
Hemolytic Uremic Syndrome (HUS)
Hemolytic uremic syndrome (HUS) can
occur after S. dysenteriae type 1
infection. Convulsions may occur in
children; the mechanism may be related
to a rapid rate of temperature elevation
51
or
metabolic
alterations,
and
is
associated with the production of the
Shiga toxin.
The Shiga Toxin
The Shiga toxin, also called the
verotoxin, is produced by Shigella
dysenteriae
and
enterohemorrhagic
Escherichia
coli
(EHEC), of which the strain O157:H7
has become the best known.
Mechanism of Action
52
The toxin acts on the lining of the blood
vessels, the vascular endothelium. The
B subunits of the toxin bind to the cell
membrane. The A subunit interacts with
the ribosomes to inactivate them. The A
subunit of Shiga toxin is an Nglycosidase that modifies the RNA
component of the ribosome to inactivate
it and so bring a halt to protein
synthesis leading to the death of the
cell. The vascular endothelium has to
continually renew itself, so this killing
of cells leads to a breakdown of the
53
lining and to hemorrhage. The first
response
is
commonly
a
bloody
diarrhea. This is because Shiga toxin is
usually taken in with contaminated food
or water.
Clostridium perfringens
C. perfringens
54
Clostridium
perfringens,
which
produces a huge array of invasins and
exotoxins, causes wound and surgical
infections that lead to gas gangrene, in
addition to severe uterine infections.
Clostridial hemolysins and extracellular
enzymes such as proteases, lipases,
collagenase
and
hyaluronidase,
contribute to the invasive process.
Clostridium perfringens also produces
an enterotoxin and is an important cause
of food poisoning. Usually the organism
is encountered in improperly sterilized
55
(canned) foods in which endospores
have germinated.
Gas gangrene
Gas gangrene generally occurs at the
site of trauma or a recent surgical
wound. The onset of gas gangrene is
sudden and dramatic. About a third of
cases occur on their own. Patients who
develop this disease in this manner
often have underlying blood vessel
disease (atherosclerosis or hardening of
the arteries), diabetes, or colon cancer.
56
Gas gangrene is marked by a high fever,
brownish pus, gas bubbles under the
skin, skin discoloration, and a foul odor.
It
can
be
fatal
if
not
treated
immediately.
Clostridium difficile
C. difficile
Clostridium difficile causes antibioticassociated diarrhea (AAD) and more
serious intestinal conditions such as
57
colitis and pseudomembranous colitis
in humans. These conditions generally
result from overgrowth of Clostridium
difficile in the colon, usually after the
normal intestinal microbiota flora has
been
disturbed
by
antimicrobial
chemotherapy.
In the hospital and nursing home
setting, C. difficile infections can be
minimized by careful use of antibiotics,
use of contact precautions with patients
with known or suspected cases of
disease, and by implementation of an
58
effective environmental and disinfection
strategy.
Clostridium tetani
C. tetani
Clostridium tetani is the causative agent
of tetanus. The organism is found in
soil, especially heavily-manured soils,
and in the intestinal tracts and feces of
various animals. The organism produces
59
terminal
spores
within
a
swollen
sporangium giving it a distinctive
drumstick appearance. Although the
bacterium has a typical Gram-positive
cell wall, it may stain Gram-negative or
Gram-variable, especially in older cells.
Tetanus is a highly fatal disease of
humans.The disease stems not from
invasive infection but from a potent
neurotoxin
(tetanus
toxin
or
tetanospasmin) produced when spores
germinate and vegetative cells grow
after gaining access to wounds. The
60
organism
multiplies
locally
and
symptoms appear remote from the
infection site.
Pathogenesis of tetanus
Most cases of tetanus result from small
puncture wounds or lacerations which
become contaminated with C. tetani
spores that germinate and produce
toxin. The infection remains localized,
often with only minimal inflammatory
damage. The toxin is produced during
61
cell growth, sporulation and lysis. It
migrates along neural paths from a local
wound to sites of action in the central
nervous system. The clinical pattern of
generalized tetanus consists of severe
painful spasms and rigidity of the
voluntary muscles. The characteristic
symptom of "lockjaw" involves spasms
of the masseter muscle. It is an early
symptom
which
is
followed
by
progressive rigidity and violent spasms
of the trunk and limb muscles. Spasms
of
the
pharyngeal
62
muscles
cause
difficulty in swallowing. Death usually
results from interference with the
mechanics of respiration.
Clostridium botulinum
C. botulinum
C. botulinum is a large anaerobic
bacillus
that
forms
subterminal
endospores. It is widely distributed in
63
soil, sediments of lakes and ponds, and
decaying vegetation.
Pathogenesis of Food-borne Botulism
In food-borne botulism, the botulinum
toxin is ingested with food in which
spores
have
germinated
and
the
organism has grown. The toxin is
absorbed by the upper part of the GI
tract in the duodenum and jejunum and
passes into the blood stream by which it
64
reaches the peripheral neuromuscular
synapses. The toxin binds to the
presynaptic stimulatory terminals and
blocks
the
release
of
the
neurotransmitter acetylcholine which is
required for a nerve to simulate the
muscle.
Bacillus anthracis and Anthrax
The
anthrax
bacillus,
Bacillus
anthracis, was the first bacterium
shown to be the cause of a disease. In
65
1877, Robert Koch grew the organism
in pure culture, demonstrated its ability
to form endospores, and produced
experimental anthrax by injecting it into
animals.
Bacillus anthracis is Gram-positive,
sporeforming rod. The bacterium can be
cultivated in ordinary nutrient medium
under aerobic or anaerobic conditions.
Genotypically and phenotypically it is
very similar to Bacillus cereus.
Anthrax
66
Gastrointestinal anthrax is similar to
cutaneous anthrax but occurs on the
intestinal mucosa. As in cutaneous
anthrax, the organisms probably invade
the mucosa through a preexisting lesion.
The bacteria spread from the mucosal
lesion
to
the
lymphatic
system.
Intestinal anthrax results from the
ingestion of poorly cooked meat from
infected
animals.
Gastrointestinal
anthrax is rare but may occur as
explosive outbreaks associated with
ingestion of infected animals. Intestinal
67
anthrax has an extremely high mortality
rate.
Bacillus cereus is a normal inhabitant
of the soil, but it can be regularly
isolated from foods such as grains and
spices. B. cereus causes two types of
food-borne intoxications (as opposed to
infections). One type is characterized by
nausea and vomiting and abdominal
cramps and has an incubation period of
1 to 6 hours. It resembles
Staphylococcus aureus food poisoning
in its symptoms and incubation period.
68
This is the "short-incubation" or emetic
form of the disease. The second type is
manifested primarily by abdominal
cramps and diarrhea with an incubation
period of 8 to 16 hours. Diarrhea may
be a small volume or profuse and
watery. This type is referred to as the
"long-incubation" or diarrheal form of
the disease, and it resembles food
poisoning caused by Clostridium
perfringens. In either type, the illness
usually lasts less than 24 hours after
onset.
69
The short-incubation form is caused by
a preformed, heat-stable emetic toxin,
ETE. The mechanism and site of action
of this toxin are unknown, although the
small molecule forms ion channels and
holes in membranes. The longincubation form of illness is mediated
by the heat-labile diarrheagenic
enterotoxin Nhe and/or hemolytic
enterotoxin HBL, which cause
intestinal fluid secretion, probably by
several mechanisms, including pore
70
formation and activation of adenylate
cyclase enzymes.
Corynebacterium diphtheriae
Diphtheria is an upper respiratory tract
illness characterized by sore throat, low
fever, and an adherent membrane
(called a pseudomembrane on the
tonsils, pharynx, and/or nasal cavity.
Diphtheria toxin produced by C.
diphtheriae, can cause myocarditis,
polyneuritis, and other systemic toxic
71
effects. A milder form of diphtheria can
be restricted to the skin.
Pathogenicity
1. Invasion of the local tissues of the
throat, which requires colonization and
subsequent bacterial proliferation. The
bacteria produce several types of pili.
2. Toxigenesis:The diphtheria toxin
causes the death eucaryotic cells and
tissues by inhibition protein synthesis in
the cells.
72
Toxigenicity
Two factors have great influence on the
ability of Corynebacterium diphtheriae
to produce the diphtheria toxin: (1) low
extracellular concentrations of iron and
(2) the presence of a lysogenic prophage
in the bacterial chromosome. The
repressor is activated by iron, and it is
in this way that iron influences toxin
production. High yields of toxin are
73
synthesized only by lysogenicbacteria
under conditions of iron deficiency.
Mycobacterium tuberculosis and
Tuberculosis
Tuberculosis
TB infection means that MTB is in the
body, but the immune system is keeping
the bacteria under control. The immune
system
does
this
by
producing
macrophages that surround the tubercle
bacilli. The cells form a hard shell that
74
keeps the bacilli contained and under
control. Most people with TB infection
have
a
positive
reaction
to
the
tuberculin skin test. People who have
TB infection but not TB disease are
NOT infectious, i.e., they cannot spread
the infection to other people. These
people usually have a normal chest xray. TB infection is not considered a
case of TB disease.
Mycobacterium bovis is the etiologic
agent of TB in cows and rarely in
75
humans. Humans can also be infected
by the consumption of unpasteurized
milk.
Atypical mycobacteria which include
mycobacteria
demonstrating
unique
properties like growth temperatures,
pigment production when grown in
either
light
(photochromogens)
or
darkness (scotochromogens) or rapidity
of
growth.
Examples
include
M.
kansasii, (photochromogenic) M. avium
and M. intracellulare, (non pigmented
76
mycobacteria
commonly
associated
with pulmonary and extrapulmonary
infections in HIV patients) and M.
chelonei, which are fast growing.
Cell Wall Structure
The
cell
wall
structure
of
Mycobacterium tuberculosis deserves
special attention because it is unique
among procaryotes, and it is a major
determinant
of
virulence
for
the
bacterium. The cell wall complex
contains peptidoglycan, but otherwise it
77
is composed of complex lipids. Over
60% of the mycobacterial cell wall is
lipid. The lipid fraction of MTB's cell
wall
consists
of
three
major
components, mycolic acids, cord factor,
and wax-D.
Resistance to anti-TB drugs can occur
when these drugs are misused or
mismanaged. Examples include when
patients do not complete their full
course of treatment; when health-care
providers prescribe the wrong
78
treatment, the wrong dose, or length of
time for taking the drugs; when the
supply of drugs is not always available;
or when the drugs are of poor quality.
Multidrug-resistant tuberculosis
(MDR TB) is TB that is resistant to at
least two of the best anti-TB drugs,
isoniazid and rifampicin. These drugs
are considered first-line drugs and are
used to treat all persons with TB
disease.
79
Extensively drug resistant TB (XDR
TB) is a relatively rare type of MDR
TB. XDR TB is defined as TB which is
resistant to isoniazid and rifampin, plus
resistant to any fluoroquinolone and at
least one of three injectable second-line
drugs (i.e., amikacin, kanamycin, or
capreomycin). Because XDR TB is
resistant to first-line and second-line
drugs, patients are left with less
effective treatment options, and cases
often have worse treatment outcomes.
80
Both MDR TB and XDR TB are more
common in TB patients that do not take
their
medicines
prescribed,
regularly
or
who
or
as
experience
reactivation of TB disease after having
taken TB medicine in the past.
Persons with HIV infection or other
conditions that can compromise the
immune system are at highest risk for
MDR TB and XDR TB. They are more
likely to develop TB disease once
infected and have a higher risk of death
from disease.
81
Actinomycetes and related bacteria
The actinomycetes are relatives of
tuberculosis and diphtheria but are
not pathogenic. Actinomycetes show
branching
and
filament
formation.
Many of the organisms can form spores,
but they are not the same as endospores.
Branched
forms
resemble
molds.
Actinomycetes such as Streptomyces
have a world-wide distribution in soils.
They
are
important
in
aerobic
decomposition of organic compounds
82
and
have
an
important
role
in
biodegradation and the carbon cycle.
Actinomycetes are the main producers
of antibiotics in industrial settings,
being the source of most tetracyclines,
macrolides (e.g. erythromycin), and
aminoglycosides
(e.g.
gentamicin, etc.).
83
streptomycin,
Spirochaetes (Spiral bacteria)
These are spiral shaped bacilli. With the
exception of a few, they generally
cannot be cultivated in the laboratory.
They are classified into three clinically
important classes.
84
Borrellia, which are relatively large
motile spirochaetes exemplified by B.
vicenti and Leptotrichia buccalis and B
recurrentis. B. vicenti and Leptotrichia
buccalis are known causative agents for
Vincents angina while B recurrentis is
associated with relapsing fever.
Lyme disease was first recognized in
the US. Lyme outbreak and the onset of
illness occur during summer and early
fall suggested that the transmission of
the disease was by an arthropod vector.
85
The
etiologic
agent
is
Borrelia
burgdorferi.
Treponema, which are relatively thinner
and more tightly coiled than Borrelia.
Typical
pallidum
examples
and
T.
are
Treponema
pertenue,
which
respectively cause syphilis and yaws.
Leptospira: These are finer and more
tightly coiled than the Treponemes.
They are classified as a single species of
86
Leptospira interrogans. Many of its
available serotypes (over 130) are
pathogenic
and
include
icterohaemorrhagiae
which
L.
causes
Weil’s disease and L. canicola which
causes lymphocytic meningitis.
Obligate Intracellular Gram-negative
bacteria
Small bacteria that require intracellular
environment
easily
for
growth and are not
cultured
in
87
diagnostic
laboratories. Important members of the
group include:
Clamydias
of
which
Clamydia
trachomatis, (causative agents for eye
disease, urethritis and cervicitis and
lymphogranuloma venereum).
C.
psittaci
(causative
agent
for
psittacosis – an uncommon respiratory
infection) and C. pneumoniae (causative
agent for an atypical pneumonia).
88
Rickettsiae and coxiellae:
Rickettsiae are obligate intracellular
gram negative bacteria with preference
for vascular endothelium. Rickettsial
diseases are associated with petechial
(vasculitic
rash)
and
multi-organ
disease.
Coxiella is a related genus that causes
acute disease (atypical pneumonia), and
chronic disease (infective endocarditis)
89
Cell-wall deficient bacteria
Mycoplasmas are a group of bacteria
that lack a cell wall. Pathogenic
important
typically
pneumoniae
species
of
mycoplasmas
include
Mycoplasma
and
Ureaplasma
urealyticum. They are not stained by
gram stain reagents and are also
resistant to the effects of β-lactam
antibiotics because of their lack of cell
wall. They cause atypical pneumonia,
upper respiratory tract infections and
central nervous system complications.
90
Most
isolates
are
sensitive
Erythromycin and Tetracycline.
91
to