1) Pathogenesis is the development of a disease caused by an infectious agent like a microbe. It involves the microbe overpowering the host's defenses through steps like transmission, colonization, adhesion, invasion, survival, and tissue injury. 2) Microbes have various mechanisms that allow them to cause disease, including producing toxins or enzymes that damage tissues or avoid host defenses. They may also form protective capsules or adhere tightly to host cells. 3) The degree of pathogenicity or ability to cause disease depends on factors like infectious dose, routes of transmission, and virulence factors that help microbes overcome host defenses.

1. Pathogenesis & Microbial
Mechanisms of Pathogenesis

2. Pathogenesis
• The word comes from the Greek pathos, "disease", and genesis, creation.
• The term pathogenesis means step by step development of a disease.
• The chain of events leading to that disease due to a series of changes in the
structure and /or function of a cell/tissue/organ.
• Caused by a microbial, chemical or physical agent.

3. Pathogenicity - Ability to cause disease
Virulence - Degree of pathogenicity
• Many properties that determine a microbe’s pathogenicity or virulence are
unclear or unknown
• But, when a microbe overpowers the hosts defenses, disease results!

4. 3. Parentarel
• Microorganisms are deposited into the tissues below the skin
or mucus membranes
• Punctures
• Injections
• Bites
• Scratches
• Surgery
• Splitting of skin due to swelling or dryness

5. Number of Invading Microbes
• LD50 - Lethal Dose of a microbes toxin that
will kill 50% of experimentally inoculated
test animal
• ID50 - infectious dose required to cause
disease in 50% of inoculated test animals
– Example: ID50 for Vibrio cholerea 108 cells
(100,000,000 cells)
– ID50 for Inhalation Anthrax - 5,000 to 10,000
spores

6. Steps involved in the pathogenesis
of the bacteria:
• 1. Transmission/Entry
• 2. Colonization
• 3. Adhesion
• 4. Invasion
• 5. Survival in the host
• 6. Tissue Injury

7. Transmission/Entry
• Potential pathogens may enter the body by various routes,
including the respiratory, gastrointestinal, urinary or genital
tracts.
• Alternatively, they may directly enter tissues through insect bites
or by accidental or surgical trauma to the skin.
• Many opportunistic pathogens are carried as part of the normal
human flora, and this acts as a ready source of infection in the
compromised host (e.g. in cases of AIDS or when the skin barrier is
breached).

8. Transmission

9. Colonization
• The establishment of a stable population of bacteria on the
host’s skin or mucous membranes is called colonization.
• For many pathogenic bacteria, the initial interaction with host
tissues occurs at a mucosal surface and colonization normally
requires adhesion to the mucosal cell surface.
• This allows the establishment of a focus of infection that may
remain localized or may subsequently spread to other tissues

10. Adhesion
• Adhesion is necessary to avoid innate host defense
mechanisms such as peristalsis in the gut and the flushing
action of mucus, saliva and urine, which remove non-adherent
bacteria.
• For bacteria, adhesion is an essential preliminary to
colonization and then penetration through tissues.
• Successful colonization also requires that bacteria are able to
acquire essential nutrients—in particular iron—for growth.

11. Adhesion
• At the molecular level, adhesion involves surface interactions
between specific receptors on the mammalian cell membrane
(usually carbohydrates) and ligands (usually proteins) on the
bacterial surface.
• The presence or absence of specific receptors on mammalian
cells contributes significantly to tissue specificity of infection.

13. Invasion
• Invasion is penetration of host cells and tissues (beyond the
skin and mucous surfaces), and is mediated by a complex array
of molecules, often described as ‘invasins’.
• These can be in the form of bacterial surface or secreted
proteins which target host cell molecules (receptors).

14. Invasion
• Once attached to a mucosal surface, some bacteria, e.g.
Corynebacterium diphtheriae or Clostridium tetani, exert their
pathogenic effects without penetrating the tissues of the host.
• These produce biologically active molecules such as toxins,
which mediate tissue damage at local or distant sites.

15. SURVIVAL IN THE HOST
• Many bacterial pathogens are able to resist the cytotoxic
action of plasma and other body fluids involving antibody and
complement (classical pathway) or complement alone
(alternate pathway) or lysozyme.
• Killing of extracellular pathogens largely occurs within
phagocytes after opsonization (by antibody and/ or
complement) and phagocytosis.

16. Mechanisms of Survival
• Capsules (many pathogens),
• Protein A (S. aureus)
• and M protein (S. pyogenes) function in this regard.

17. TISSUE INJURY
• Bacteria cause tissue injury primarily by several distinct
mechanisms involving:
• Exotoxins
• Endotoxins and non-specific immunity
• Specific humoral and cell mediated immunity

18. How do Bacterial Pathogens
penetrate Host Defenses?
1. Adherence - almost all pathogens
have a means to attach to host tissue
Binding Sites
adhesins
ligands

19. How Bacterial Pathogens Penetrate Host Defenses
• 1. Adherence
• 2. Capsule
• 3. Enzymes
– A. leukocidins
– B. Hemolysins
– C. Coagulase
– D. Kinases
– E. Hyaluronidase
– F. Collagenase
– G. Necrotizing Factor

20. Adhesins and ligands are usually on
Fimbriae
• Neisseria
gonorrhoeae
• ETEC
(Entertoxigenic E. coli)
• Bordetella pertussis

21. 2. Capsules
• Prevent phagocytosis
• Attachment
• Streptococcus
pneumoniae
• Klebsiella pneumoniae
• Haemophilus
influenzae
• Bacillus anthracis
• Streptococcus mutans
• Yersinia pestis
K. pneumoniae

22. 3. Enzymes
• Many pathogens secrete enzymes that contribute to their
pathogenicity

23. A. Leukocidins
• Attack certain types of WBC’s
• 1. Kills WBC’s which prevents phagocytosis
• 2. Releases & ruptures lysosomes
– lysosomes - contain powerful hydrolytic enzymes which then
cause more tissue damage

24. B. Hemolysins - cause the lysis of RBC’s
Streptococci

25. 1. Alpha Hemolytic Streptococci
- secrete hemolysins that cause the
incomplete lysis or RBC’s

26. 2. Beta Hemolytic Streptococci
- Secrete hemolysins that cause the complete lysis of RBC’s

27. C. Coagulase - cause blood to coagulate
• Blood clots protect bacteria from phagocytosis from WBC’s and
other host defenses
• Staphylococci - are often coagulase positive
– boils
– abscesses

28. D. Kinases - enzymes that dissolve blood clots
• 1. Streptokinase - Streptococci
• 2. Staphylokinase - Staphylococci
• Helps to spread bacteria - Bacteremia
• Streptokinase - used to dissolve blood clots in the Heart (Heart Attacks due to
obstructed coronary blood vessels)

29. E. Hyaluronidase
• Breaks down Hyaluronic acid (found in connective tissues)
• “Spreading Factor”
• Mixed with a drug to help spread the drug through a body
tissue

30. F. Collagenase
• Breaks down collagen (found in many connective tissues)
• Clostridium perfringens - Gas Gangrene
– uses this to spread thru muscle tissue

31. G. Necrotizing Factor
- Causes death (necrosis) to tissue cells
“Flesh Eating Bacteria”

32. Bacterial Toxins
• Poisonous substances produced by
microorganisms
• Toxins - primary factor - pathogenicity
• 220 known bacterial toxins
– 40% cause disease by damaging the Eukaryotic cell
membrane
• Toxemia
– Toxins in the bloodstream

33. Types of Toxins
• 1. Exotoxins
– Exotoxins are generated by the bacteria and actively
secreted
– Secreted outside the bacterial cell
• 2. Endotoxins
– Part of the outer cell wall of Gram (-) bacteria
– The body's response to endotoxin can involve severe
inflammation.

34. Exotoxins
• Mostly seen in Gram (+) Bacteria
• Heat labile, can be inactivated by heating at 60-80
۠ C.
• Excreted [ secreted] from the microbial cells into
the surrounding ie culture media or circulatory
system
• Don’t require bacterial death or cell lysis for their
release.

35. Types of Exotoxins
• 1. Cytotoxins
– Kill cells- shigella, vibrio
• 2. Neurotoxins
– Interfere with normal nerve impulses
– Clostridium botulinum
– Clostridium tetani
• 3. Enterotoxins
– Effect cells lining the G.I. Tract
– E. coli
– Salmonella

36. Response to Toxins
• If exposed to exotoxins: antibodies against the toxin (antitoxins)
• Exotoxins inactivated ( heat, formalin or phenol) no longer cause
disease, but stimulate the production of antitoxin
– altered exotoxins - Toxoids
• Toxoids - injected to stimulate the production of antitoxins and provide
immunity

37. Endotoxins
• Part of the Gram (-) Bacterial cell wall.
• Biological activity or toxicity of endotoxin is largely
due to lipid A.
• Relatively heat stable can withstand heat over 60 ۠
C for many hours.
• Released upon cell lysis or death.
• Less potent than exotoxins, active in large doses
only.
• Pyrogenic often produce fever in hosts.
• Salmonella, Shigella, Escherichia, Neisseria.

38. Bacteriocin
• Bacteriocins were first discovered by A. Gratia in 1925.
• He called his first discovery a colicine because it killed E.
coli.
• Bacteriocins are proteinaceous toxins produced by
bacteria to inhibit the growth of similar or closely
related bacterial strain(s).
• They are typically considered to be narrow spectrum
antibiotics, though this has been debated.

39. • Medical significance
• Bacteriocins are of interest in medicine because
they are made by non-pathogenic bacteria that
normally colonize the human body.
• Loss of these harmless bacteria following antibiotic
use may allow opportunistic pathogenic bacteria to
invade the human body.