Pathogenicity of Microorganisms

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Chapter 30

• Pathogenicity of Microorganisms

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Host-Parasite Relationships

• Symbiosis
• the living together of two organisms in a
  variety of relationships
• commensalism
• mutualism
• parasitism
• Saprophytic organisms
• obtain nutrients from dead or decaying organic
  matter
• some are pathogenic but most are considered
  scavengers

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Parasites

• Parasites are organisms that live on or within a
  host organism and are metabolically dependent on
  the host
• types of parasites
• ectoparasite
• lives on surface of host
• endoparasite
• lives within host

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Types of Hosts

• Final host
• host on (or in) which parasite either gains
  sexual maturity or reproduces
• Intermediate host
• serves as temporary but essential environment for
  some stage of parasites development
• Transfer host
• is not necessary for development but serves as
  vehicle for reaching final host
• Reservoir host
• nonhuman organism infected with a parasite that
  can also infect humans

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Parasitism and Disease

• Infection
• growth and multiplication of parasite on or
  within host
• Infectious disease
• disease resulting from infection
• Pathogen
• any parasitic organism that causes infectious
  disease
• Primary (frank) pathogen causes disease by
  direct interaction with healthy host
• Opportunistic pathogen part of normal flora and
  causes disease when it has gained access to other
  tissue sites or host is immunocompromised
• Pathogenicity
• ability of parasite to cause disease

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Factors Impacting Outcome of Host-Parasite
Relationships

• Factors
• number of organisms present
• the degree of virulence of pathogen
• virulence factors
• e.g., capsules, pili, toxins
• hosts defenses or degree of resistance

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Table 30.1
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Figure 30.1 Mathematical Expression of Infection
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Virulence

• Virulence
• degree or intensity of pathogenicity
• determined by three characteristics of the
  pathogen
• invasiveness
• ability to spread to adjacent tissues
• infectivity
• ability to establish focal point of infection
• pathogenic potential
• degree to which pathogen can cause damage to host

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Aspects of Pathogenic Potential

• Toxigenicity
• ability to produce toxins
• Immunopathology
• ability to trigger exaggerated immune responses

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Measuring Virulence

• Lethal dose 50 (LD50)
• number of pathogens that will kill 50 of an
  experimental group of hosts in a specified time
• Infectious dose 50 (ID50)
• number of pathogens that will infect 50 of an
  experimental group of hosts in a specified time

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Figure 30.2Determination of LD 50 Strain A LD
50 is 30, B LD 50 is 50 hence, A is more
virulent.
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Pathogenesis of Viral Diseases

• Fundamental process of Viral infection in a host
  cell
• maintain reservoir a place to live and multiply
  before infection
• enter host
• contact and enter susceptible cells
• replicate within cells
• release from host (immediate or delayed)

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Viral infection

• spread to adjacent cells
• Evade host immune response
• be cleared from body of host, establish
  persistent infection, or kill host
• be shed back into environment

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Maintaining a Reservoir

• most common reservoir of human viruses are humans
  and other animals
• some viruses are acquired early in hosts life
  and cause disease later
• most often, viruses are transmitted from one host
  to another host and cause infection in a short
  time frame

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Viral Entry

• Occurs at a variety of sites
• via body surface
• via sexual contact, needle sticks, blood
  transfusions, and organ transplants
• via insect vectors
• organisms that transmit pathogen from one host to
  another

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Adsorption

• Adsorption
• attachment to the cell surface
• results from binding of viral protein to host
  cell receptors
• binding of virus to receptor results in cell
  penetration or delivery of viral nucleic acid to
  host cell cytoplasm

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Entry of Human Virus Nucleic Acids into Host Cell

• Direct entry of nucleic acid
• e.g., polio virus- enters the host cell and
  deliver viral nucleic acid into the cytoplasm of
  cell
• It enters through the human gastrointestinal
  tract but produces diseases in the central
  nervous system. endocytosis and release of
  nucleic acid from capsid (uncoating)
• e.g., pox viruses- causes small pox
• Fusion of viral envelope
• e.g. influenza fusion of viral envelope with
  cell membrane of host

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Primary Replication

• Primary replication
• some replicate at site of entry, cause disease at
  same site, and do not spread throughout body
• others spread to distant sites and then replicate
• e.g., polio viruses enter through
  gastrointestinal tract but produce disease in
  central nervous system

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Evasion of Host Defenses

• begins when the virus first infects the host
• for the virus to cause a successful infection, it
  must be able to avoid host immunity so it can
  spread to a sufficient number of host cells to
  amplify the number of virions

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Viral Spread and Cell Tropism

• Viral spread vary but most common is by
  bloodstream and lymphatic system
• Viremia- presence of virus in blood
• Spread by way of nerves e.g rabies
• Tropisms
• Viruses exhibit cell, tissue, and organ
  specificities

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Virus-Host Interactions

• Cytopathic viruses
• local necrosis with ultimate host death
• alternatively, can trigger apoptosis (programmed
  cell death) i.e host cell dies, often before
  viral replication can occur
• Noncytopathic viruses
• cause latent or persistent infections

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Non-Cytopathic Viruses

• Do not immediately cause cell death
• cause latent or persistent infections
• productive non-cytopathic viruses
• produce persistent infection with the release of
  only a few new particles at a time
• nonproductive non-cytopathic viruses
• do not actively make virus at detectable levels
  for a period of time (latent infection)
• these viruses may become productive by
  environmental stressors or other factors

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Other Outcomes of Virus-Host Interaction

• Clinical illness
• some tissues can be quickly repaired after viral
  damage
• e.g., intestinal epithelium
• others cannot be easily repaired
• e.g., tissues of central nervous system
• Integration of viral DNA
• may result in transformation of host cells into
  cancerous cells due to viral DNA interference
  with host DNA growth cycle regulation

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Virus Shedding

• last step in infectious process is shedding of
  the virus in the environment
• needed for maintenance of viral source in a host
  population
• often occurs at same body surface used for entry
  of the virus
• at this stage host is very contagious/infectious/
  stay far..can spread
• in some infections, host is dead (end of host)
  and no shedding occurs-e.g Rabies

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Pathogenesis of Bacterial Diseases

• Maintain a reservoir
• Like viral infection Bacteria too need a place
  to live before and after causing infection
• initial transport to/entry into host
• adhere to, colonize, and/or invade host

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Bacterial infection

• initially evade host defenses
• multiply or complete life cycles on or in host
• damage host
• leave host and return to reservoir or enter new
  host

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Maintaining a Reservoir of the Bacterial Pathogen

• For human pathogens, most common reservoirs are
• other humans
• animals
• environment

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Transport of the Bacterial Pathogen to the Host

• Direct contact
• e.g., coughing, sneezing, body contact
• Indirect contact
• vehicles (e.g., soil, water, food)
• arthropod vectors
• fomites inanimate objects that harbor and
  transmit pathogens

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Attachment and Colonization by the Bacterial
Pathogen

• Adherence structures
• Structures such as such as pili and fimbriae and
  specialized adhesion molecules on bacteriums
  cell surface bind to complementary receptor sites
  on host cell surface
• Colonization
• Colonization is the establishment of a site of
  microbial reproduction on or within host
• does not necessarily result in tissue invasion or
  damage

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Evasion of Host Defenses by Bacteria

• Successful pathogens can evade destruction by
  host
• by
• Formation of capsule- Neisseria gonorrhoeae
• production of leukocidins- substance that
  destroy phagocytes before phagocytosis can occur
  Streptoccocus pneumoniae, Staphyloccocus
• use of an actin tail (cytoskeleton protein) to
  spread into neighboring cells and escape
  destruction e.g Shigella
• Lysosomal enzymes- Mycobacterium tuberculosis
  resist these enzymes probably because of itd waxy
  external layer.

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Endotoxins
Table 30.4-Bacterium polymerised host actin into
long tail and for propulsion from one cell to
another and out of the host.
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Bacterial Invasiveness

• Varies among pathogens
• e.g., Clostridium tetani (tetanus) produces a
  number of virulence factors (e.g toxin and
  proteolytic enzymes ) but is non-invasive i.e it
  does not spread from one tissue to another.
• e.g., Bacillus anthracis (anthrax) and Yersinia
  pestis (plague) also produce many virulence
  factors ( capsule toxins) and are highly
  invasive
• e.g., Streptococcus spp. span the spectrum of
  virulence factors and invasiveness

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Growth and Multiplication of the Bacterial
Pathogen

• occurs when pathogen finds appropriate
  environment within host
• some pathogens actively grow in blood plasma
• bacteremia presence of viable bacteria in blood
• septicemia presence of bacteria or their toxins
  in blood

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Intracellular Pathogens

• Bacteria that are able to grow and multiply in
  various cells of a host
• Facultative intracellular pathogens
• can live within host cells or in the environment
• e.g., Brucella abortus can grow independently as
  well as in macrophages, neutrophils and
  trophoblast cells
• Obligate intracellular pathogens
• incapable of growth and multiplication outside of
  a host
• eg., viruses and rickettsia

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Leaving the Host

• must occur if microbe is to be perpetuated
• most bacteria leave by passive mechanisms
• in feces, urine, droplets, saliva

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Regulation of Bacterial Virulence Factor
Expression

• Often environmental factors control expression of
  virulence genes
• e.g., Corynebacterium diphtheriae
• gene for diphtheria toxin regulated by iron
• e.g., Bordetella pertussis
• expression of virulence genes increased at body
  temperature
• e.g., Vibrio cholerae
• gene for cholera toxin regulated by pH,
  temperature and other factors

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Pathogenicity Islands

• Pathogenicity Islands- large segments of DNA that
  carry virulence genes
• acquired during evolution of pathogen by
  horizontal gene transfer
• e.g., genes for type III secretion system (TTSS)
• enables gram-negative bacteria to secrete and
  inject virulence proteins into cytoplasm of
  eucaryotic host

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Toxigenicity

• Intoxications
• diseases that result from entry of a specific
  preformed toxin into host
• Toxin
• specific substance that damages host
• two main categories in bacteria
• exotoxins
• endotoxins
• Toxemia
• condition caused by toxins in the blood of host

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Exotoxins

• Exotoxins - soluble, heat-labile, proteins and
  usually released into the surroundings as
  bacterial pathogen grows
• humans exposed to exotoxins in three main ways
• ingestion of preformed exotoxin
• bacterial colonization of a mucosal surface
  followed by exotoxin production
• colonization of a wound or abscess followed by
  local exotoxin production
• most exotoxin producers are gram-positive
• often travel from site of infection to other
  tissues or cells where they exert their effects

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Types of Exotoxins

• AB exotoxins- composed of two subunits
• A subunit responsible for toxic effect once
  inside the host cell
• B subunit binds to target cell od host
• specific host site exotoxins-e.g neurotoxin
• membrane- disrupting exotoxinspore- e.g forming
  exotoxins
• Superantigens (enterotoxin of staph) that
  stimulate T cells directly to make cytokines

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AB Exotoxins

• Composed of two subunits
• A subunit responsible for toxic effect once
  inside the host cell
• B subunit binds to target cell

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Specific Host Site Exotoxins

• can be AB toxins
• neurotoxins
• target nerve tissue
• e.g., botulinum toxin
• enterotoxins
• target intestinal mucosa
• e.g., cholera toxin
• cytotoxins
• target general tissues
• e.g., nephrotoxin

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Membrane-Disrupting Exotoxins

• do not have separable A and B subunits
• two types
• pore-forming exotoxins
• Phospholipases-lyses the plasma membrane e.g-
  Clostridium perfringens-gas gagresn

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Some Pore-Forming Exotoxins

• Bacterial Toxins that forms pores in the
  membranes
• Leukocidins membrane-disrupting toxins
• kill phagocytic leukocytes- pneumococci. Strepto,
  staphyloccus
• Hemolysins- other toxin that form pores in
  membranes of blood cells
• kill erythrocytes, leukocytes, and many other
  cells
• e.g., streptolysin-O (SLO)- a hemolysin from
  Streptococcus pyogenes- oxygen-sensitive
• e.g., streptolysin-S (SLS)- oxygen-stable

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Hemolytic Reactions

• beta-hemolysis
• complete lysis
• observed as zone of clearing around colony on
  blood agar
• alpha-hemolysis
• partial lysis
• observed as greenish zone around colony on blood
  agar

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Phospholipase Enzymes

• Phospholipase Enzymes a second subtype of
  membrane-disrupting toxins
• remove charged head group from lipid part of
  phospholipids in host-cell plasma membranes
• membrane destabilizes, cell lyses and cell death

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Endotoxins

• Lipopolysaccharide (LPS) in gram-negative outer
  membrane can be toxic to specific hosts
• called endotoxin because it is bound to bacterium
  and released when organism lyses and some is also
  released during multiplication
• toxic component is the lipid portion

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Polymicrobial Diseases

• Polymicrobial Diseases -many infectious diseases
  involve the interactions of more than one
  infectious agent
• these diseases can be polyviral, polybacterial,
  combined viral-bacterial, or polymycotic or
  protozoan
• Dental infections are examples of polybacterial
  disease

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Dental Infections

• Dental Infections -caused by various
  odontopathogens
• Formation of dental plaque creates environment
  for pathogens that produce acids and other
  virulence factors

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Figure 30.9 Plaque Development Process
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Figure 30.11-Microscopic Appearance of Plaque
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Periodontal Disease

• Periodontitis
• initial inflammatory response to plaque bacteria
  and tissue destruction
• leads to swelling of tissue and formation of
  periodontal pockets
• Periodontosis
• bone destruction caused by colonization of
  periodontal pockets

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Periodontal Disease

• Gingivitis
• inflammation of gingiva caused by colonization of
  periodontal pockets
• Treatment, prevention, and control
• oral surgery and antibiotic therapy in some cases
• plaque removal and good dental hygiene

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Bibliography

• Lecture PowerPoints Prescotts Principles of
  Microbiology-Mc Graw Hill Co.
• http//en.wikipedia.org/wiki/Scientific_method
• https//files.kennesaw.edu/faculty/jhendrix/bio334
  0/home.html