Mechanisms of Pathogenicity

1
Mechanisms of Pathogenicity

• Introduction
• Entering the Host
• Penetrating Host Defenses
• Damaging Host Cells

2
Pathogenicity - Introduction

• Pathogenicity is the ability of a pathogen to
  produce disease by overcoming host defenses
• Virulence is the degree of pathogenicity
• Expressed as LD50 (lethal dose necessary to kill
  50 of the inoculated hosts)
• ID50 is also used (dose necessary to infect 50
  of the inoculated hosts)

3
Pathogenicity Entering Host

• Route of entry is called Portal of Entry
• Usual portals include mucous membranes
• Conjunctiva (eyes)
• Respiratory tract
• Gastrointestinal tract
• Genitourinary tract

4
Pathogenicity Entering Host

• Respiratory most common
• Microorganisms are inhaled on moisture droplets
  or dust particles
• Genitourinary through mucous membranes and direct
  contact
• Gastrointestinal through food, water and
  contaminated fingers

5
Pathogenicity Entering Host

• Most microorganisms cannot penetrate skin but can
  gain access through hair follicles and sweat
  ducts
• Can gain entry through inoculation also called
  parenteral
• insect bites
• injections
• wounds

6
Penetrating Host Defenses

• Bacterial Elements that Overcome Host Defenses
• Capsules
• Cell Wall Components
• Enzymes
• Cytoskeletal Components

7
Penetrating Host Defenses

• Capsules
• Prevent or reduce phagocytosis
• Usually polysaccharide
• Examples
• Dextran (S. mutans)
• Polyglutamic acid (B. anthracsis)

8
Penetrating Host Defenses

• Cell Wall Components
• Adhesins (adhere to complementary receptors on
  host cells
• Fimbriae interact with membrane glycoproteins
  especially mannose
• Some microbes reproduce only in host cells

9
Penetrating Host Defenses

• Enzymes
• Leukocidins destroy white blood cells
• Hemolysins destroy red blood cells
• Kinases digest blood clots
• Hyaluronidase digests mucopolysccharides
• Collogenase destroy collogen of connective
  tissue

10
Penetrating Host Defenses

• Via Cell Cytoskeleton
• Invasins
• Cause actin of microfilaments to form basket to
  carry bacteria into cell
• Found in Salmonella

11
Damaging Host Cells

• Damage by metabolizing and reproducing in hosts
• Damage by the production of toxins
• Two major types of toxins
• Endotoxins
• Exotoxins

12
Damaging Host Cells

• Exotoxins
• Usually from Gram positive bacteria
• Usually a secreted protein product
• Heat Labile (60 to 80 deg C)
• Very toxic low LD50
• Usually specific for cell type or cell function
• Can be neutralized by antibodies
• Symptoms usually appear sooner

13
Damaging Host Cells

• Exotoxins Examples
• Diptheria toxin stops protein sysnthesis
  damages heart and other organs
• Cholera toxin affects intestinal cells disrups
  cAMP a cell secondary messenger
• Tetnus toxin affects nerve transmission
• Toxic shock affects T-cells macrophages
• Listeriolysin pore forming cytotoxin allows
  cell to escape phagocytic vesicle

14
Damaging Host Cells

• Endotoxins
• Almost exclusively Gram negative
• Present in LPS and released with destruction of
  cell
• Heat stable often can withstand autoclave
• Not easily neutralized by antibodies
• Produces general effects fever, aches, shock
• Much larger LD50 than exotoxins

15
Damaging Host Cells

• Endotoxins Examples
• Salmonella typhi and typhoic fever-incubation
  period 1 week symptoms due to LPS induced
  release of cytokines enter blood and multiply in
  spleen and liver
• S. enteriditis S. typhimurium food borne
  gastroenterits symptoms usually appear within
  24 to 48 hours takes longer than with S. aureus
  exotoxin