1. Pathogenicity of Microorganisms
Chapter 33
Pathogenicity of Microorganisms

2. 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

3. Factors impacting outcome of host-parasite relationships
number of organisms present
the degree of virulence of pathogen
virulence factors
e.g., capsules, pili, toxins
host’s defenses or degree of resistance

4. 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

5. Aspects of pathogenic potential
toxigenicity
ability to produce toxins
immunopathology
ability to trigger exaggerated immune responses

6. Pathogenesis of Viral Diseases
maintain reservoir
enter host
contact and enter susceptible cells
replicate within cells
release from host (immediate or delayed)
spread to adjacent cells
engender host immune response
be cleared from host, establish persistent infection, or kill host
be shed back into environment

7. Maintaining a Reservoir
Where do they live before they are transmitted?
most common reservoir of human viruses are humans and other animals
some viruses are acquired early in host’s life and cause disease later
most often, viruses are transmitted from one host to another host and cause infection in a short time frame

8. 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

9. Adsorption adsorption
attachment to the cell surface
results from binding of viral protein ligands to host cell receptors
binding of virus to receptor results in cell penetration or delivery of virtal nucleic acid to host cell cytoplasm

10. Entry of Human Virus Nucleic Acids into Host Cell
direct entry of nucleic acid
e.g., polio virus
endocytosis and release of nucleic acid from capsid (uncoating)
e.g., pox viruses
fusion of viral envelope with cell membrane and subsequent uncoating
e.g. influenza

11. 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 track but produces disease in central nervous system

12. Release from Host Cells
host cell lysis
replication of viral particles increases within host cell until cell membrane cannot contain all the material within
results in large number of viral particles released at the same time
budding or “blebbing”
replicated viral particle becomes enclosed in host cell membrane which is then called the viral envelope
release of viral particles is a slower process than lysis

13. Viral Spread and Cell Tropism
usually spread by blood stream and lymphatic system
viremia
presence of virus in blood
tropisms
cell, tissue, and organ specificities

14. Pathogenesis of Bacterial Diseases
maintain a reservoir
place to live before and after causing infection
initial transport to/entry into host
adhere to, colonize, and/or invade host
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

15. Maintaining a Reservoir of the Bacterial Pathogen
for human pathogens, most common reservoirs are:
other humans
animals
environment

16. 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

17. Attachment and Colonization by the Bacterial Pathogen
adherence
mediated by special molecules or structures called adhesins
colonization
establishment of a site of microbial reproduction on or within host
does not necessarily result in tissue invasion or damage

18. Attachment and Colonization by the Bacterial Pathogen
adherence structures
such as pili and fimbriae and specialized adhesion molecules on bacterium’s cell surface bind to complementary receptor sites on host cell surface
are a type of virulence factor
colonization
establishment of a site of microbial reproduction on or within host
does not necessarily result in tissue invasion or damage

19. fimbriae
TEM of fimbriated E. coli.
Figure 33.3 (a)

20. Invasion of the Bacterial Pathogen
can be active penetration of host’s mucous membranes or epithelium
can be passive penetration
e.g., skin lesions, insect bites, wounds
once below mucous membrane, bacterium can spread to deeper tissues
involves production of specific products and/or enzymes that promote spreading

21. Bacterial Invasiveness
varies among pathogens
e.g., Clostridium tetani (tetanus) produces a number of virulence factors but is non-invasive
e.g., Bacillus anthracis (anthrax) and Yersinia pestis (plague) also produce many virulence factors and are highly invasive

22. 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

23. Intracellular Pathogens
obligate intracellular pathogens
incapable of growth and multiplication outside of a host
eg., viruses and rickettsia

24. Leaving the Host most bacteria leave by passive mechanisms
in feces, urine, droplets, saliva,

25. Toxigenicity intoxications toxin toxemia
diseases that result from entry of a specific preformed toxin into host
toxin
specific substance that damages host
toxemia
condition caused by toxins in the blood of host

26. Toxigenicity intoxications toxin toxemia
diseases that result from a specific toxin produced by bacteria. Some toxins are only produced during host infection
toxin
specific substance that damages host
toxemia
condition caused by toxins in the blood of host

27. Exotoxins soluble, heat-labile, proteins
usually released into the surroundings as bacterial pathogen grows
most exotoxin producers are gram-negative
often travel from site of infection to other tissues or cells where they exert their effects

28. More About Exotoxins
usually synthesized by specific bacteria that have toxin genes in their plasmids or prophage DNA
Corynebacterium diphtheriae -diphtheria
among the most lethal substances known
are highly immunogenic
can stimulate production of neutralizing antibodies (antitoxins)
can be chemically inactivated to form immunogenic toxoids
e.g., tetanus toxoid

29. Some pore-forming exotoxins
leukocidins
kill phagocytic leukocytes
hemolysins
kill erythrocytes, leukocytes, and many other cells
e.g., streptolysin-O (SLO)
oxygen-sensitive
e.g., streptolysin-S (SLS)
oxygen stable

30. Hemolytic reactions beta-hemolysis alpha-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

31. 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 dies
Clostridium perfringens

32. 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 dies
Clostridium perfringens

33. Figure 33.6 (b)

34. Endotoxins
lipopolysaccharide in gram-negative cell wall 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, lipid A

35. More about Endotoxins heat stable toxic (nanogram amounts)
weakly immunogenic
generally similar, despite source
cause general system weakness, diarrhea, inflammation, intestinal hemorrhage, and fibrinolysis, the enzymatic breakdown of fibrin, themajor protein component of blood clots septic shock

36. Host Defense Against Microbial Invasion
in host-pathogen relationships survival strategies have co-evolved
host has many niches for microbes which adapt to the various environmental conditions present in the body
host also has a variety of barriers to defend itself from microbial invasion

37. Figure 33.8

38. Primary Defenses
to be effective, must limit bacterial entry without limiting essential functions of host
e.g., skin has many layers with glands present that produce anti-microbial substances; normal flora also protect host
e.g., mucous membranes with cilia
e.g. pH regulation (skin slightly acidic)
e.g., flushing mechanisms
e.g., additional antimicrobial substances produced where host tissues interface with the environment

39. Secondary Defenses
consists of soluble anti-microbial products, cells capable of sensing and responding to invading microbes and long-term memory
host blood and interstitial fluids contain anti-microbial proteins
processes such as complement activation, inflammation, fever and phagocytosis

40. Factors Influencing Host Defenses
age, stress, nutritional deficiencies and genetic background can influence primary and secondary immune responses of host
long-term exposure to environmental pollutants, drug abuse, or certain prescribed medicine can inhibit normal host defenses against infection

41. Microbial Mechanisms for Escaping Host Defenses
numerous mechanisms for both viral and bacterial pathogens

42. Evasion of Host Defenses by Viruses
mutations that change antigenic sites or alter expression of antigens
infection of immune system cells, diminishing their function

43. Evasion of Host Defenses by Bacteria
have mechanisms to resist complement system, phagocytosis, and specific immune responses

44. Evading the complement system
capsules
lengthened O-chains
serum resistance
modified lipooligosaccharides interfere with formation of membrane attack complex

45. Resisting phagocytosis
capsules
production of specialized surface proteins that block adherence of phagocytes to bacterium
production of leukocidins that destroy phagocytes
production of proteases that cleave complement factor C5a (phagocyte chemoattractant)