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MICROBIAL PATHOGENESIS
INTRODUCTORY LECTURE
BY WALTER WASWA
WALTER WASWA
• Pathogenicity and Virulence
– Pathogenicity
• The ability of a microbe to cause disease
• This term is often used to describe or compare species
– Virulence
• The degree of pathogenicity in a microorganism
• This term is often used to describe or compare strains within a species
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DEFINATIONS
• Pathogen is a microorganism that is able to cause disease in a plant, animal or insect.
• Pathogenicity is the ability to produce disease in a host organism.
• Microbes express their pathogenicity by means of their virulence, a term which refers to the degree of pathogenicityof the microbe.
• Determinants of virulence of a pathogen are any of its genetic or biochemical or structural features that enable it to produce disease in a host.
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• Acute infection vs. chronic infection
– Acute Infection
• An infection characterized by sudden onset, rapid progression, and often with severe symptoms
– Chronic Infection
• An infection characterized by delayed onset and slow progression
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• Clinical infection vs. subclinical infection
– Clinical Infection
• An infection with obvious observable or detectable symptoms
– Subclinical Infection
• An infection with few or no obvious symptoms
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• Opportunistic infection
– An infection caused by microorganisms that are commonly found in the host’s environment. This term is often used to refer to infections caused by organisms in the normal flora
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• The suffix “-emia”
– A suffix meaning “presence of an infectious agent”
• Bacteremia = Presence of infectious bacteria
• Viremia = Presence of infectious virus
• Fungemia = Presence of infectious fungus
• Septicemia = Presence of an infectious agent in the bloodstream
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• The suffix “-itis”
– A suffix meaning “inflammation of”
• Examples:
–Pharyngitis = Inflammation of the pharynx
–Endocarditis = Inflammation of the heart chambers
–Gastroenteritis = Inflammation of the gastointestinal tract
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• Reservoir of Infection
– The source of an infectious agent
• Carrier
– An individual who carries an infectious agent without manifesting symptoms, yet who can transmit the agent to another individual
• Fomites
– Any inanimate object capable of being an intermediate in the indirect transmission of an infectious agent
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– Animal Vectors
– An animal (nonhuman) that can transmit an infectious agent to humans
– Two types: mechanical and biological
– Mechanical animal vectors: The infectious agent is physically transmitted by the animal vector, but the agent does not incubate or grow in the animal; e.g, the transmission of bacteria sticking to the feet of flies
• Biological animal vectors: The infectious agent must incubate in the animal host as part of the agent’s developmental cycle; e.g, the transmission of malaria by infected mosquitoes
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• Localized infection vs. systemic infection
– Localized Infection
• An infection that is restricted to a specific location or region within the body of the host
– Systemic Infection
• An infection that has spread to several regions or areas in the body of the host
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• The relationship between a host and a pathogen is dynamic, since each modifies the activities and functions of the other.
• The outcome of such a relationship depends on: the virulence of the pathogen and
• the relative degree of resistance or susceptibility of the host, mainly due to the effectiveness of the host defense mechanisms
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Infectious Agents in Humans
• Prion - scrapie
• Viruses – HIV, influenza
• Bacteria – Mycobacterium tuberculosis
• Fungi – Candida albicans
• Protozoa – Plasmodium falciparum
• Helminths – Schistosoma mansoni
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normal abnormal
Prion
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Virus
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Bacteria
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Fungi
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Protozoa
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Helminths
Ascaris lumbricoides : human intestinal roundworm
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Barriers
Physical barrier: Skin, Mucosal gel overlaying epithelium (respiratory, gastrointestinal, urogenitary)
Microbiological barrier: Normal microbioflora
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Initiation of Disease
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Transmission
• Aerosols to respiratory mucosa
• Fomite to nasopharyngial or conjungtive mucosa
• Fecal – Oral Route
• Mucosal surface to mucosal surface
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Transmission
Multiplication
Dissemination
Invasion
Breach of epithelium
Colonization of mucosa
Infectious Disease Cycle
or
Attachment to target cells
to subepithelial or intracellular space
Evasion ofhost defense
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Evasion/Manipulation of Host Defense
• Modulation of innate/inflammatory response
• Resistance to phagocytic killing in subepithelial space
• Serum resistance
• Antigenic variation
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Resistance to phagocytic killing in subepithelial space
• Survive within phagocyte
• Inhibit phagocyte mobilization :(chemotaxis, complement activation)
Inhibit chemoattractants: Streptococcus pyogenes degrades C5a
Inhibit chemotaxis: Pertussis toxin causes intracellular rise in cAMP in neutrophils to impair chemotaxis
• Avoid ingestion
kill phagocytes: Streptolysin O lyses PMNs; Staphylococcus aureus alpha, beta and gamma toxins and leucocidin lyses PMNs
capsular protection from opsonization: M proteins, Streptococcus pyogenes
Bacterial capsules that resemble self: Neisseria meningitidis (sialic acid); Streptococcus pyogenes (hyaluronic acid)
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Survival within phagocyte
Escape endosome or phagolysosome:
- Shigella, Listeria monocytogenes
Inhibit phagosome-lysosome fusion
- Legionella pneumophila, Mycobacterium tuberculosis, Salmonella
Survive within phagolysosome (resist enzymatic degration or
neutralize toxic products)
- Inactivate reactive oxygen species: Salmonella, via superoxide dismutase, catalase, recA
- Resist antimicrobial peptides: Host cationic peptides complexed with SapA peptide
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Cell and Tissue Damage
• Induction of apoptosis and necrosis
• Virus-induced cytopathic effect
• Induction of damaging host immune response
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Cell lysis
accumulation of reactive
oxygen intermediatesmacrophages
virusesaccumulation of nitrogen
intermediates
accumulation of intracellular
calcium
Rotavirus,
cytomegalovirus, HIV
Syncytia
formation
Paramyxoviruses
(respiratory syncytial
virus, parainfluenza
viruses, measels virus,
herpesvirus, some
retroviruses)
viral-encoded
fusion proteins
Virus-Induced Cytopathic Effect: Part 1
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production of
eosinophilic or
basophilic
inclusion
bodies
viruses
host cell
transformation
DNA viruses
Burkitt's
lymphoma
(EBV)
inactivation of p53 and Rb,
chromosomal destabilization,
enhancement of foreign DNA
integration and mutagenecity
cervical
carcinoma
(human
papilloma
viruses)
retroviruses
adult T-cell
leukemia
(human T-cell
lymphotropic
virus type 1)
Virus-Induced Cytopathic Effect: Part 2
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Induction of Damaging Host Immune Response
autoimmune
response
cross-reactivity between self
and mycobacterial heat shock
proteins
cross-reactivity between
components of endocardium
and joint synovial membrane
molecules and antigens in the
streptococcus cell wall
Acute rheumatic
fever after group A
streptococcal
pharyngitis
hypersensitivity
reactions
granuloma
formation
Mycobacterium
tuberculosis
septic
shock/sepsisbacteria
LPS, peptidoglycan,
lipoteichoic acid,
toxins acting as
superantigenstoxic shock
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The end
QUESTIONS?
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