Lecture 4

Pathogenesis of
Bacterial Infection
 Pathogenesis

A microorganism is a pathogen if it is capable of

causing disease; however, some organisms are
frequently pathogens, whereas others cause disease
rarely.

Opportunistic pathogens are those that rarely if ever

cause disease in immunocompetent people but can
cause serious infections in immunocompromised
patients.
 Pathogenesis

These opportunists are frequently members of the body’s

normal flora.

Virulence is a quantitative measure of pathogenicity and is

measured by the number of organisms required to cause
disease.

50% lethal dose (LD50) is the number of organisms needed

to kill half the hosts and the 50% infectious dose (ID) is
the number needed to cause infection in half the hosts.
 Pathogenesis

The infectious dose of an organism required to cause

disease varies greatly among the pathogenic
bacteria.

For example:
Shigella and Salmonella both cause diarrhea by
infecting the gastrointestinal tract but the infectious
dose of Shigella is less than 100 organisms whereas
the infectious dose of Salmonella is on the order of
100,000 organisms.
 Pathogenesis

The infectious dose of bacteria depends primarily on

their “virulence factors.”

For example:
Whether their pili allow them to adhere well to
mucous membranes, whether they produce
exotoxins or endotoxins, whether they possess a
capsule to protect them from phagocytosis and
whether they can survive various nonspecific host
defense such as acid in the stomach.
 Pathogenesis

Parasite refers to the parasitic relationship of the

bacteria to the host cells; that is, the presence of the
bacteria are detrimental to the host cells.

Bacteria that are human pathogens can be thought of,

therefore, as parasites.
 Pathogenesis

Some bacterial pathogens are obligate intracellular

parasites, e.g. Chlamydia and Rickettsiae, because
they can grow only within host cells.

Many bacteria are facultative parasites because they

can grow within cells, outside cells, or on
bacteriologic media.
 Types of Bacterial Infections

Bacteria cause disease by two major mechanisms:

1) Toxin production
2) Invasion and inflammation
 Disease Bacterium Mechanism

Gas gangrene C. perfringens One exotoxin (cytotoxin)

& food & other causes massive red blood cell
poisoning species of destructions (hemolysis);
Clostridium another exotoxin
(enterotoxin) is related to
food poisoning and causes
diarrhea

Diphtheria C. diphtheriae Cytotoxin inhibits protein

synthesis, especially in nerve,
heart, and kidney cells
Cholera V. cholerae Enterotoxin causes secretion
of large amounts of fluids
and electrolytes that result in
diarrhea
 Disease Bacterium Mechanism
Botulism C. botulinum Neurotoxin prevents the
transmission of nerve
impulses, flaccid paralysis
results

Tetanus C. tetani Neurotoxin blocks nerve

impulses to muscle
relaxation that results in
uncontrollable muscle
contractions

Scarlet fever S. pyogenes Cytotoxins causes

vasodilation that result in the
characteristic rash
 Disease Bacterium Mechanism
Scalded skin S. aureus One exotoxin causes skin
syndrome, layers to separate and slough
food poisoning, off (scalded skin); another
and toxic shock exotoxin (enterotoxin)
syndrome produces diarrhea and
vomiting; still another
exotoxin produces symptoms
associated with TSS

Traveller’s ETEC and Enterotoxin causes secretion

diarrhea Shigella of large amounts of fluids
species and electrolytes that result in
diarrhea
 Enzymes

Coagulase Leukocidins
(Panton-Valentine)

Kinases

Hyaluronidase Collagenase
 Diseases

Microorganism establishes itself and multiplies.

Infections spread directly through the tissues or

through the lymphatic system into the blood.
 Diseases

Infectious disease refers to an infection with functional

and structural harm to the host that is usually
accompanied by signs and symptoms.

Infection – entrance and multiplication of a

microorganism in or on a host.

Microorganism may enter the host through many

routes. Including the RT, GIT, or breaks in the skin.
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Severity or Duration of a Disease
 Severity or Duration of a Disease

Subacute disease – disease that is intermediate

between acute and chronic (SSPE)

Latent disease – is one in which the causative agent

remains inactive for a time but then becomes active
to produce symptoms of the disease (shingles)
Occurrence of a Disease (Sporadic)

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Occurrence of a Disease (Endemic)

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Occurrence of a Disease (Epidemic)

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Occurrence of a Disease (Pandemic)

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 Extent of Host Involvement

Local infection is one in which the invading microorganisms

are limited to a relatively small area of the body. (boils)

Focal infection, agents of local infection enter a blood or

lymphatic vessel and spread to other specific parts of the
body, where they are confined to specific areas of the body.

Systemic (generalized) infection, microorganisms or their

products are spread throughout the body by the blood or
lymph. (measles)
 Extent of Host Involvement

Septicemia –presence of actively multiplying bacteria

in the blood

Bacteremia – presence of bacteria in the blood and if

the bacteria actually multiply in the blood – sepsis.

Toxemia refers to presence of toxins in the blood.

Viremia refers to the presence of viruses in the blood.

 Extent of Host Involvement

Primary infection is an acute infection that causes the

initial illness.

Secondary infection is one caused by an opportunistic

pathogen after the primary infection has weakened
the body’s defenses.

Pneumocystis pneumonia as a consequence of AIDS –

example of secondary infection
 Extent of Host Involvement

Subclinical (inapparent) infection is one that does not

cause any noticeable illness.

Poliovirus and hepatitis A virus, for example, can

be carried by people who never develop the illness.
 Type of Bacterial Infections

Chronic carrier state, in

which the organisms
continue to grow with or
without producing
symptoms in the host.

Chronic carriers, eg. Typhoid

Mary – important source
of infection of others –
public health hazard.
 Occurrence of a Disease

Prevalence of a disease is the number of people in a

population who develop a disease at a specified
time, regardless of when it first appeared.

Takes into account both old and new cases, an indicator

of how seriously and how long a disease affects a
population.
 Occurrence of a Disease

Incidence of a disease is the number of people in a

population who develop a disease during a particular
time of period, an indicator of the spread of the
disease
 Types of Bacterial Infections

The determination of whether an organism recovered

from a patient is actually the cause of the disease
involves an awareness of two phenomena:
1. Normal flora are permanent residents of the
body and vary in type according to anatomic site.

When an organism is obtained from a patient’s

specimen, the question of whether it is a member of
the normal flora is important in interpreting the
finding.
 Types of Bacterial Infections

2. Colonization refers to the presence of a new

organism that is neither a member of the normal
flora nor the cause of symptoms.

It can be a difficult clinical dilemma to distinguish

between a pathogen and a colonizer, especially in
specimens obtained from the respiratory tract, such
as throat cultures and sputum cultures.
 Stages of Bacterial Pathogenesis

A generalized sequence of the stages of infection

1) Transmission from an external source

2) Evasion of primary host defenses such as skin or

stomach acid

3) Adherence to mucous membranes, usually by

bacterial pili
 Stages of Bacterial Pathogenesis

4) Colonization by growth of the bacteria at the site of

adherence

5) Disease symptoms caused by toxin production or

invasion accompanied by inflammation
 Stages of Bacterial Pathogenesis

6) Host responses, both nonspecific and specific

immunity, during steps 3, 4 and 5

7) Progression or resolution of the disease

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 Clinical Microbiology

Patient’s medical history, physical examination, results

of x-rays, laboratory tests and epidemiological
information (previous infections, travel and illness in
the family)
 Clinical Microbiology
Begins when the patient
presents signs of
infection to the
physician. Initial
diagnosis is made and
the physician then
orders diagnostic
medical and laboratory
procedures.
 Culture
Direct stain Antibiotic Susceptibility
 Clinical Microbiology

Early diagnosis is associated with early treatment and a

better prognosis for the patient.

Presumptive identification … antibiotic therapy

can be initiated
Final definitive identification …. update the report
 Clinical Microbiology

All pathogens in a specimen must be identified and

reported.

Pathogen (bacteria, viruses, fungi and parasites)

capable of causing infectious disease.

Normal flora – microorganisms normally residing in a

particular body site, generally do not cause disease.
 Status of the hosts’ immune system
Protection from microbial invasion
Inherent microbial factors

Disease
 Host-Microbes Relationships

The normal microbiota can prevent pathogens from

causing an infection; this phenomenon is known as
microbial antagonism.

Normal microbiota and the host exist in symbiosis

(living together)
 Host – Microbes Relationships

Three types of symbiosis are commensalism (one

organism benefits and the other is unaffected)

Mutualism (both organisms benefit)

Parasitism one organism benefits and one is harmed)

Pathogenesis of Infectious Disease
Some species of the usual microbial flora may be
opportunists, capable of causing disease in an
immunocompromised host
Pathogenesis of Infectious Disease

Immune response may be reduced or altered

* Suppression by immunosuppresive drugs,
chemotherapy or radiation
*Individuals with lymphoma, leukemia or
blood disorders
*With chronic illnesses such as diabetes or
severe hepatic disease (cirrhosis)
Host defense against Infectious
Disease
The usual microbial flora benefits the normal
host by
*priming the immune system
*out-competing potential pathogens for
nutrients, and
*creating a hostile environment for other
microbes
 Predisposing Factors

Make the body more susceptible to a disease &

may alter the course of the disease

Gender, age, fatigue, environment, habits, lifestyle,

preexisting illness, chemotherapy & emotional
disturbances

Females have a higher incidence of urinary tract

infections than males; whereas males have higher rates
of pneumonia and meningitis.
 Pat t e r n s of Dis e as e

I n c u bat io n per io d Pr o dr o mal I l n es s Dec lin e Conv a le s c e nc e

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 Host Resistance Factors

• Physical, mechanical and chemical barriers

• Components of the Immune System
Phagocytes, complement, cytokines, and the
products of inflammation
• Components of the adaptive immune response
Antibodies & the Lymphocytes
Microbes’ mechanisms to evade the
host’s defenses
• Evasion of phagocytosis
• Production of enzymes & endotoxins
• Induction of tolerance in the adaptive immune
system or suppression of the adaptive immune
system
• Avoid recognition by the adaptive immune system
by varying the antigens