Module 2.

PATHOGENESIS (HOST-
MICROBE INTERACTION)
MLS 2309 | CLINICAL BACTERIOLOGY
College of Medical Laboratory Science | Central Philippine University

The human gut teems with bacteria,

many of their species still unknown.
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 LEARNING OUTCOMES
REFERENCE At the end of this module, the learner should
BAILEY AND SCOTT’S have been be able to:
DIAGNOSTIC
MICROBIOLOGY 1 Explain properly the pathogenesis of
bacterial infections including mode of
transmission and pathogenic/virulence
factors.
CHAPTER 3
Host-
Microorganism Identify correctly body sites with normal
2 flora
and discuss the predominant normal
Interaction flora in each body site.

3
Explain comprehensively the beneficial
and harmful effects of normal flora.
 PATHOGENESIS
Pathogenesis To understand the
concepts in the
pathogenesis of
• The origination and infectious diseases,
development of a disease understanding of
the host-pathogen
relationship is
important.
Terminologies
Host Parasite
Pathogens Vectors
Carriers Virulence
Fomites Reservoir
 Host-microbe
Relationship
MUTUALISM – host and organism
benefit from one another;
symbiosis

COMMENSALISM – organism
benefits from host without
causing harm

PARASITISM – one organism

ARE BACTERIA PARASITES? benefits at the expense of
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another
 Host-microorganism interactions

Encounter Colonization Invasion and

and entry dissemination Outcome
and entry
Host-microorganism
Pathogen encounters Pathogen multiplies Pathogen invades deeper Pathogen completes interactions and
and colonizes host and breaches host tissues and disseminates, cycle:
surface surface defenses encounters inflammatory — Leaves host stages of infection
and immune responses — Destroys host or disease
— Remains in latent state
— Is destroyed by host

Corresponding infection-disease stages

Incubation Prodromal Clinical Stage of Convalescent

stage stage stage decline stage

No signs or First signs and Peak of Condition of host Full recovery of

symptoms symptoms, characteristic deteriorates surviving host
pathogen may signs and symptoms possibly to death or chronic infection
be highly of infection or or signs and develops, or death
communicable disease symptoms begin to
subside as host
condition improves

Figure 3-12 Host-microorganism interactions and stages of infection or disease.

MODE OF MICROORGANISM SOURCES
TRANSMISSION Humans, animals, food, water, air, soil

• Means where human host MODE OF

acquire the microbial TRANSMISSION
agent
HUMAN HOST
• Disease transmission can
occur by:
A. Direct Contact
WHY IS THIS IMPORTANT?
B. Indirect Contact
Determine optimum
specimens for organism
• Some microbes may have isolation.
multiple mode of Minimize risk of laboratory-
transmission acquired infections.
 DIRECT CONTACT

Horizontal Vertical
Transmission Transmission

Human or
Sexual Respiratory Mother to Mother to
animal
intercourse Droplets fetus newborn
contact

Gonorrhea, Neonatal
Gastroenteritis,
syphilis, Pertussis, Listeriosis, conjunctivitis
mumps,
chlamydia, common cold syphilis, AIDS (gonorrhea,
measles
AIDS chlamydia)
 INDIRECT CONTACT

Fomites Vehicle Transmission Vector Transmission

Mechanical Biological
Food Water Aerosols
vector vector

Tetanus, Cholera, Typhoid Lyme

Gastrenteritis
hepatits B, leptospirosis, TB, measles, fever, disease,
, hepatitis A,
athletes cryptospori- valley fever trachoma, west nile,
amoebiasis
foot diosis shigellosis malaria
 Infection
process where a parasitic organism
enters into a prolonged relationship
with the host
According to According to Host According to
Cause Distribution Extent of Infection
• Autogenous • Local • Acute
• Iatrogenic • Focal • Chronic
• Opportunistic • Systemic • Mixed
• Nosocomial infection
HOST DEFENSE MECHANISM
Overview of the Immune System
Physical
barriers
1st line of External
defense component
Biochemical
barriers
Natural
Immunity
Cellular
component
2nd line of Internal
IMMUNITY defense Component
Fluid
component
Cellular
Immunity
Acquired 3rd line of
Immunity defense
Humoral
immunity
Microbial Factors Contributing
to Pathogenesis and Virulence
Virulence factors are characteristics that
enable bacteria to cause disease(s).

1 Ability to resist phagocytosis

Surface structures that promote

2 adhesion to host cells and tissues

3 Ability to survive intracellularly and

proliferate

4 Ability to produce extracellular

toxins and enzymes
Antiphagocytic
Factors
• Surface protein A
which binds to the Fc
portion of IgG
• S. aureus

• Polysaccharide
capsules
• S. pneumoniae, N.
meningitidis
Macrophage
ingesting bacteria
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Adherence
Factors
1. Pili/fimbriae
2. Adherence proteins
3. biofilms
4. Adhesins/ligands
For bacteria to cause diseases, it must
penetrate the mucus layer and attach to
epithelium.
Host cells produce the necessary receptors for
adhesion.
Invasion and
Dissemination EXAMPLES
1. C. diphtheriae invades
epithelium of naspharynx
•Invasion is the process causing sore throat
of penetrating and 2. L. monocytogenes
growing in tissues invade the intestinal
mucosa, then
disseminates
3. L. pneumophila infects
•Dissemination is the pulmonary
spread of microorganisms macrophages and
to distant body sites causes pneumonia
 ENDOTOXIN EXOTOXIN
Found in Gram-neg. Mostly Gram-pos.
Composition Lipids Protein
Part of CW, released only
Production Produced extracellularly
when cells are lysed
Heat stability Stable Labile
Fever Yes No
Pharmacologic
Not specific Specific
effect
Toxicity/
Low High (toxoids)
Antigenicity
Lethal dose Large Small
Endotoxins
• Pathophysiologic effects are similar
regardless of bacterial origin

• Following can be observed:

1. Fever, leukopenia and REPRESENTATIVE
hypoglycemia INFECTIONS
2. Hypotension and shock Typhoid fever
3. Intravascular coagulation UTI
Meningococcal
4. Death from massive organ
dysfunction meningitis
Exotoxins
Pathophysiologic
effects are specific
• C. tetani tetanospasmin
causes spastic paralysis.
• C. botulinum toxin leads
to lack of muscle
contraction and
paralysis.
• V. cholerae enterotoxin
causes rapid excretion
of electrolytes into the AB Exotoxin Transport Mechanisms
small bowel A subunit provides the toxic activity
B subunit adherence and aids entrance of
exotoxin into host cell
Enzymes
1. Collagenase – C. perfringens, spread of infection
2. Coagulase – S. aureus, prevents phagocytosis
3. Hyaluronidase – Staphylococcus and
Streptococcus, spread of infection
4. Cytolysins – Hemolysin (SLO), leukocidin
(Staphylococcus)
5. IgA proteases – N. gonorrhoeae, N. meningitidis,
H. influenzae and S. pneumoniae
 Attributed to Various Microorganisms
Host Defense Mechanism of Evasion Example

Summary of Hydrodynamic flow Attachment Fimbriae, surface proteins, lipoteichoic acid

pseudomembrane of diphtheria
Defenses of the Mucus barrier Attachment
Penetration
Mannose-sensitive fimbriae

Human or Animal Deprivation of essential nutrients

Lysozyme in secretions
Systems of high-affinity uptake
Resistance to lysis
Iron metabolism
Substitution of peptidoglycan

Host to Infection
Surface immunoglobulins Absent or low immunogenicity Hyaluronic acid, capsules
Antigenic heterogeneity Fimbriae, capsules, LPS, M protein, etc.
Masking of antigens Capsules, IgA-binding proteins

and Evasion Unbroken surface (epithelial cell

Destruction
Penetration
IgA protease
Neisseria gonorrhoeae, Shigella spp.

Mechanisms surface)
Unknown defenses in lymphatics N. gonorrhoeae, Shigella spp.
(intercellular space)
Attributed to Serum defenses
Recognition by antibody Antigenic heterogeneity Fimbriae, capsules, LPS, M protein

Various Masking of antigen

Destruction of antibody
Capsules, Ig-binding proteins
Borrelia

Microorganisms
Adapted from Gotschlich
EC: Thoughts on the
evolution of strategies
used by bacteria for
evasion of host defenses,
Rev Infect Dis 5:S779, 1983.
LPS, Lipopolysaccharide.
Antigenic variation
Complement system Failure to activate alternative pathway
Inactivation of complement components
Resistance to bacteriolysis
Formation of abscess
Localization
Fibrin tapping Fibrinolysis
Abscess formation Collagenase, elastase
Secondary immune response Nonspecific B-cell activation
Inhibition of delayed hypersensitivity
Rapidly fatal (toxin)
Phagocytosis Inhibition of chemotaxis
Inhibition of attachment and ingestion
Inhibition of metabolic burst
Inhibition of degranulation
Resistance to permeability inducing cationic
protein
Resistance to oxidative attack
Escape from phagosome
Destruction of phagocyte
Sialic acid capsules
Cleavage of C3b in empyema fluids
CoIV plasmid
Bacteroides fragilis capsule
Streptococcus spp.
Pseudomonas, Clostridium
LPS, lipoprotein
Anergy of miliary tuberculosis
Anthrax, plague, Clostridium
Brucella, Salmonella, Neisseria, Staphylococcus, Pseudomonas
Capsules, M protein, Ig-binding proteins, gonococcal pili
Salmonella typhi
Mycobacteria
Gram-positive cell wall, smooth LPS, polyanionic capsules
Catalase, superoxide dismutase, carotenoid pigments
Mycobacterium bovis, Legionella pneumophila
Streptococcus pneumoniae, Streptococcus pyogenes,
Staphylococcus aureus, Pseudomonas aeruginosa

Adapted from Gotschlich EC: Thoughts on the evolution of strategies used by bacteria for evasion of host defenses, Rev Infect Dis 5:S779, 1983.
 Prevention of Infectious Diseases

Immunization Epidemiology
• Can be active or passive • Tracking and
characterizing infections
and infectious diseases

Prophylactic • Monitors the effect

diseases have on public
Antimicrobial Therapy health
• Administration of antibiotic
when the risk is high
 NORMAL FLORA

• Microorganisms that inhabit

many surfaces of the human
body
1. Transient colonizers – survive,
but do not multiply; shed with
the host cells.
2. Resident flora – survive, thrive
and multiply; presence is
more permanent.
NORMAL MICROBIAL
FLORA IN HUMANS

Normal flora
organisms frequently
are found in clinical
specimens.
ü Contamination of
sterile specimens
during collection
ü Organism is involved
in the infection
 Normal flora Normal flora
ADVANTAGES DISADVANTAGES

Stimulate antibody-mediated May be a source of infection to

immune response other individuals

Produce important substances Can share nutrients and drug

(vitamin K and B12) resistance to pathogens

Inhibit and kill pathogens by Can cause disease when they

production of enzymes fatty acids, change their usual anatomic
peroxides, bacteriocins, etc. location

Prevent colonization by pathogens

Can act as opportunistic pathogens
through competitive exclusion
VAGINAL FLORA. Vaginal Gram smear showing budding
yeast (long arrow), epithelial cells (short arrow) and a
mixture of other bacterial morphologies. The long
Gram- positive rods are most likely lactobacilli.
Centers for Disease Control and Prevention (CDC)
THANK YOU!