PATHOLOGY

1. BY
M S . J I GI S H A P A N C H O L I
H E A D
D E P T . O F B I O C H E M I S T R Y & M I C R O B I O L O G
Y I N D I A N I N S T I T U T E O F A Y U R V E D I C
P H A R M A C E U T I C A L S C I E N C E S
GU J A R A T A Y U R V E D U N I V E R S I T
Y J A M N A GA R
Mechanism of Bacterial
Pathogenesis

2. Introduction

3. Introduction
⚫ Humans and animals have abundant bacterial flora that are
usually harmless.
⚫ A general balance exists between host and his environment.
⚫ The host- parasite interaction is influenced by host factors as
well as the infecting microbe.
⚫ The outcome of this interaction can range from no
demonstrable effect to death.
⚫ Majority of the free living organisms are saprophytes.

4. Definitions

5. Commensal
⚫Commensals live in complete harmony with the
animal body (host) without causing any harm to it.
⚫The commensals constitute the normal bacterial
flora of the body, such as S. epidermidis of skin and
E. coli of gastrointestinal tract.
⚫They subsist on secretions, food residues or waste
products of the body.
⚫They serve important functions in their hosts, like
production of vitamins, protection of host from
colonisation with pathogenic organism etc.

6. Opportunistic Pathogen
⚫These are the commensals or saprophytes which can
produce disease when the body resistance is lowered.
⚫Example:
⚫Candida albicans – a causal agent of opportunistic
oral and genital infections in humans
⚫Staphylococcus aureus- occurs as commensal on
human skin but may cause Staph infections

7. Pathogen
⚫A micro organism capable of producing disease is
called as pathogen.
⚫Pathogenicity is the ability of a class of bacteria
(Pathogen) to produce disease.
⚫Examples:
⚫Bacillus anthracis causes anthrax
⚫Clostridium tetani causes tetanus
⚫Salmonella typhi causes typhoid

8. Virulence
⚫Virulence is
pathogenicity
the measure
and depends
of the degree of
on invasiveness and
toxigenecity of the organism.
⚫The ability of a bacteria to cause disease is described
in terms of the number of infecting bacteria, the
route of entry into the body, the effects of host
defense mechanisms and intrinsic characteristics of
the bacteria called as virulence factors.

9. Infection
⚫Infection may be defined as lodgement and
multiplication of an infectious agent in the body.
⚫All infections do not invariably result in disease.
symptoms (disease) after break down
others may lead to development of signs
of
⚫Some infections may remain asymptomatic and
and
host-
parasite relationship in favour of the parasite.

10. Portal of Entry
⚫The infectious agent enters the body by one of the
following routes:
⚫Oral
⚫Respiratory
⚫Genitourinary
⚫Conjunctiva
⚫Cutaneous

11. Incubation Period
⚫The time interval between the entry of the infectious
agent and the onset of clinical manifestations of
disease is called incubation period.
⚫The infective agent, after reaching the selective
tissue, undergoes multiplication during this period.
⚫The period may be as short as minutes to as long as
thirty years in the case of variant Creutzfeldt- Jakob
disease

12. Clinical Manifestation
⚫ An infection that does not cause any detectable
manifestation is known as in apparent or subclinical
infection.
⚫ A person with symptomless infection is called as carrier.
⚫ In some diseases, either because of inadequate treatment
or immune response, the infectious agent us not
eliminated, leading to carrier state.
⚫ Carriers may be temporary or chronic.

13. ⚫ Temporary carrier state lasts for less than six months,
whereas the chronic carrier is the one who excretes
the disease producing organisms for indefinite period of
several years or throughout life.
⚫ Examples: Cholera, polio, diphtheria, meningitis, typhoid
etc.
⚫ Following infection, some pathogens may remain in
latent or dormant form in host tissues and proliferate
when host resistance is lowered producing clinical
disease. This is called as Latent infection. Example:
HIV

14. ⚫ Primary infection is referred to the first or initial
infection caused by an infecting organism.
⚫ Subsequent infections by the same parasite in the host is
called as re infection.
⚫ When the body resistance of a patient is lowered by a pre
existing infectious disease or during some treatment, a
new micro organism sets up an infection which is called
as secondary infection. Example: A vaginal yeast
infection after taking antibiotics to remove bacterial
infection.

15. ⚫ When a new infection from patient or healthy staff
carrier is set up in an already diseased person, it is called
as cross infection.
⚫ Cross infections acquired in hospitals are called as
hospital acquired or nosocomial infections.
⚫ Infection where the typical or characteristic
manifestations of a particular disease is lacking, it is
called as atypical infection. Eg: Atypical mycobacterial
infections in HIV patients
⚫ An iatrogenic infection is defined as physician
induced infection resulting from drug therapy or
diagnostic procedure, eg. Hepatitis B following blood
transfusion.

16. Evolution of Infection
⚫ From the portal entry the parasites may directly invade the
tissue or may pass through lymphatic channels into blood
stream for dissemination into internal organs.
⚫ In majority of the instances, the parasites get destroyed by
the host defense mechanisms.
⚫ When the host resistance fails, an acute inflammatory
response is developed which is characterized by vascular
dilatation, marked exudation of plasma and accumulation
of leucocytes with the formation of pus.
⚫ The pus forming bacteria are termed pyogenic, eg. S.
aureus, S. pyogenes.

17. CAPSULE
ADHESINS
INVASIVENESS
EXOENZYMES
TOXINS
Bacterial Virulence factors

18. Capsule
⚫ Capsule is one of the most
important virulence
factors.
⚫ They surround many
bacterial cells which shield
the bacteria from immune
and phagocytic response.
⚫ They are made up of either
carbohydrates or proteins

19. ⚫ Capsule inhibits
phagocytosis by means of
several ways:
⚫ 1. Capsule prevents
interaction between
antibody and C3 bound to
outer
bacteria
membrane
and
respective receptors
of
their
on
phagocytic cells.
⚫ Complement activation is
inhibited by the capsule.
⚫

20. Adhesins
⚫The pathogenesis of many bacteria depend on the
ability to adhere to mucosal cells as a first step.
⚫With adhesion factors, many bacteria adhere to
epithelial or endothelial cell linings of bladder,
intestine and blood vessels.
⚫Types: Pili
Lipopolysaccharide
M proteins

21. ⚫ Pili: in most cases pili serve
as adhesion factor. Many of
the adhesin proteins are
present at the tip of pili and
binds tightly to the target
tissue.
of bacteria
pili as adhesion
⚫ Examples
producing
factor:
⚫ E.coli
⚫ Neisseria gonorrhoeae
⚫ Lipopolysaccharides: They
are present in the outer
membrane of gram –ve
bacteria.

22. ⚫ M protein: the
expression of M proteins
on the cell membrane of
bacteria mediates their
adherence to epithelial
cells as
pyogenes
seen
that
pharyngitis,
appears to be
in S.
causes
which
directly
related to the production
of M proteins.

23. Invasiveness
⚫ Invasiveness of bacteria appears to be multifactorial and
complex process. Invasive bacteria either destroy the
barrier or penetrate into the cells of the barrier.
⚫ Examples:
⚫ 1. Shigella: a series of invasive proteins are involved:
a. Proteins called as “invasion plasmid antigens
(IPA)” expressed on outer membrane permit the
bacterium to bind to the luminal surface of mucosal M
occurs
cells of intestine then endocytosis
followed by rapid exit of the
which is
bacterium from the
endosome into the cytoplasm.

24. b. Another protein, known as
“intracellular spread protein
(ICS)” expressed on the outer
membrane of the bacterium,
allows to interact with the
host cell integrins.
Following interaction, the
bacterium travels towards the
cell membrane which forms a
protrusion and fuses with cell
membranes of adjacent cells,
thereby enabling Shigella to
diffuse from cell to cell.

25. ⚫2. Enteropathogenic Yersinia: they secrete an
invasion protein which promotes binding of bacteria
to the host cells, which in turn stimulates the cell to
invaginate and take in the bacteria.
⚫3. Neisseria gonorrhoea: with its pili adhere to
mucosal cells. The bacteria also contains an enzyme
that dissolves mucosal cell lining and thereby
enables the organism to penetrate submucosal
tissues.

26. Exoenzymes
⚫ Many bacteria release enzymes that can damage host tissue in
a variety of mechanisms:
⚫ 1. Enzymes that break down collagen (eg.: collagenase,
hyaluronidase) and fibrin (eg: fibrinolysins) allows better
penetration of microbes into tissues.
⚫ 2. Enzymes that break down cellular material (Eg: proteases,
lecithinases) are associated with many Clostridia
⚫ 3. Enzymes that modify and inactivate antibiotics (eg. Beta
lactamase) hydrolyses the beta lactum ring of the antibiotics.
The beta lactamase for penicillin and cephalosporin are called
penicillinase and cephalosporinase respectively.

28. Toxins
⚫Bacterial toxins directly harm tissue or trigger
destructive biological activities.
⚫They are classified into two categories: Exotoxins
and Endotoxins

29. Exotoxins
⚫They are proteins produced and released extra
cellularly from the bacterial cell to cause toxicity.
⚫They are produced by both Gram +ve and Gram –ve
bacteria.
⚫In many cases the toxin is encoded by the plasmid,
eg: LT and ST toxins of E.coli, tetanus toxin of Cl.
tetani or a lysogenic phage, eg: C. diphtheriae, Cl.
botulinum

31. ⚫ Most exotoxins have two
structural domains, “A”
subunit (active
domain)that causes cell
cytotoxicity and “B”
domain (binding domain)
subunit that binds the A
domain to specific cellular
receptors.
⚫ “A “subunit is transferred
to the interior of the cell,
where the cell injury is
induced

32. Functional types of Exotoxins
⚫Enterotoxins: Affect gastrointestinal tract and
include cholera toxin, E.coli toxin
⚫Neurotoxins: Affect nervous system and include
botulinum toxin, tetanus toxin
⚫Cytotoxin: Affect cells in a variety of tissues and
include diphtheria toxin, pseudomonas toxin A

33. Identification of exotoxins
⚫ Ileal loop test: Ligated loops
of ileum are inoculated with
enterotoxin producing bacteria
(V. cholerae, Enterotoxigenic
E.coli), accumulation of fluid
occur in the lumen in the
organism is toxigenic.
⚫ Cell culture test: to
monolayers of sensitive cells
(eg: Vero cells) bacteria free
culture filtrate is added and
incubated. The monolayer will
be disrupted if the filtrate
contains toxin (eg Vero
cytotoxin of E.coli)

34. ⚫ Serological test (Immunoassay): Since the enterotoxin
are immunogenic, antisera can be used to detect the
presence of toxin in specimens (eg: faecal material) or in
culture media
⚫ Molecular method: for detection of DNA of toxin
producing organism in specimens are now being developed.

35. Endotoxins
⚫ They are lipopolysaccharides (LPS) present on Gram –ve bacterial
cell wall.
⚫ The lipid A portion of LPS is responsible for endotoxin activity.
⚫ They are the integral part of the bacteria and are released as
bacteria lyse.
⚫ They are primarily responsible for sepsis and septic shock.
⚫ Endotoxin mediated toxicity include: Fever, activation of
complement, thrombocytopenia, disseminated intra vascular
coagulation, decreased peripheral circulation and perfusion of
organs, shock and death

37. Infecting Dose
⚫ Adequate number of bacteria is needed for successful infections
⚫ The dose of infection depends on virulence of bacteria,
organisms of high virulence can produce severe infection in small
numbers
⚫ Bacterial virulence is the sum total od invasiveness to tissues,
capacity of multiplication in tissues and production of toxin
⚫ Minimum lethal dose (MLD) is the minimum number or
weight of organisms or toxin in micrograms needed to kill a
particular species of animal when administered by a certain
route.

38. ⚫ Minimum infecting dose (MID) is the minimum
number of bacteria required to produce clinical evidence of
infection in a susceptible animal when administered under
standard condition.
⚫ LD 50 and ID 50
⚫ Organisms like S. typhi can infect in small doses while S.
typhimurium require large number of organisms to make
infection

39. ⚫ Enhancement in virulence is called exaltation which can
be achieved by serial passage in susceptible hosts.
⚫ Reduction of virulence is termed are attenuation which
can be attained by serial passage of the organism through
un favourable hosts, prolonged storage, growth under high
temperature, repeated cultures in artificial media and in
presence of weak antiseptic substances.