Microbial Mechanisms of Pathogenicity

 

Introduction

 

1. Pathogenecity is the ability of a pathogen to produce a disease by overcoming the defenses of the host.
2. Virulence is the degree of pathogenicity.

 

How Microorganisms Enter A Host

 

1. The specific route by which a particular pathogen gains access to the body is called a portal of entry.

 

Portals of Entry

 

1. Mucous membranes
1. Respiratory tract

                                                              i.      Microorganisms that are inhaled with droplets of moisture and dust particles gain access to the respiratory tract.

                                                            ii.      The respiratory tract is the most common portal of entry.

2. Genitourinary tract

                                                              i.      Microorganism that gain access via the genitourinary tract can enter the body through mucous membranes.

3. Gastrointestinal tract

                                                              i.      Microorganisms enter the gastrointestinal tract via food, water, and contaminated fingers.

4. Conjunctiva
1. Skin
1. Most microorganisms cannot penetrate intact skin; they enter hair follicles and sweat ducts.
2. Some fungi infect the skin itself.
2. Parenteral
1. Some microorganisms can gain access to tissues by inoculation through the skin and mucous membranes in bites, injections, and other wounds. 

 

The Preferred Portal of Entry

 

1. Many microorganisms can cause infections only when they gain access through their specific portal of entry.

 

Numbers of Invading Microbes

 

1. Virulence can be expressed as LD50 (lethal dose for 50% of the inoculated hosts) or ID50 (infectious dose for 50% of the inoculated hosts).

 

Adherence

 

1. Surface projections on a pathogen called adhesions (ligands) adhere to complementary receptors on the host cells.
2. Ligands can be glycoproteins or lipoproteins and are frequently associated with fimbriae.
3. Mannose is the most common receptor.

 

How Bacterial Pathogens Penetrate Host Defenses

 

Capsules

 

1. Some pathogens have capsules that prevent them from being phagocytized.

 

Components of the Cell Wall

 

1. M protein of Streptococcus pyogenes.
1. Proteins in the cell wall can facilitate adherence or prevent a pathogen from being phagocytized.
2. Waxes in cell wall of Mycobacterium tuberculosis.
1. Some microbes can reproduce inside phagocytes.

 

Enzymes

 

1. Leukocidins destroy neutrophils and macrophages.
2. Hemolysins lyse red blood cells.
3. Local infections can be protected in a fibrin clot caused by the bacterial enzyme coagulase.
4. Bacteria can spread from a focal infection by means of kinases (which destroy blood clots), hyaluronidase (which destroys a mucopolysaccharide that holds cells together), and collagenase (which hydrolyzes connective tissue collagen).

 

Penetration into the Host Cell Cytoskeleton

1. Salmonella bacteria produce invasins, proteins that cause the actin of the host cell’s cytoskeleton to form a basket to carry the bacteria into the cell.

 

How Bacterial Pathogens Damage Host Cells

 

1. Bacteria damage host cells three ways:
1. Direct damage
2. Toxins
3. Hypersensitivity reactions

 

Direct Damage

 

1. Host cells can be destroyed when pathogens metabolize and multiply inside the host cell.

 

The Production of Toxins

 

1. Poisonous substances produced by microorganisms are called toxins; toxemia refers to the presence of toxins in the blood. The ability to produce toxins is called toxigenicity.
2. Exotoxins are produced by bacteria (mostly gram-positive) and released into the surrounding medium. Exotoxins, not the bacteria , produce the disease symptoms.
1. Antibodies produced against exotoxins are called antitoxins.
2. Cytotoxins

                                                              i.      Diphtheria toxin (which inhibits protein synthesis) – Corynebacterium diphtheriae

                                                            ii.      Erythrogenic toxins (which damage capillaries) – Streptococcus pyogenes

3. Neurotoxins

                                                              i.      Botulinum toxin (which prevents nerve transmission) – Clostridium botulinum

                                                            ii.      Tetanus toxin (which prevents inhibitory nerve transmission) – Clostridium tetani

4. Enterotoxins - induce fluid and electrolyte loss from host cell

                                                              i.      Vibrio cholerae toxin

                                                            ii.      Staphylococcus aureus - staphylococcal enterotoxin

3. Endotoxins are lipopolysaccharides (LPS), the lipid A component of the wall of gram-negative bacteria.
1. Bacterial cell death, antibiotics, and antibodies may cause the release of endotoxins.
2. Endotoxins cause fever (by inducing the release of interleukin-1) and shock (because of a TNF-induced decrease in blood pressure).

                                                              i.      TNF causes edema by damaging capillaries.

                                                            ii.      LPS stimulates release of NO from macrophages, which causes vasodilation.

3. Endotoxins allow bacteria to cross the blood-brain barrier. 
4. The Limulus amoebocyte lysate (LAL) assay is used to detect endotoxins in drugs and on medical devices.\
5. Organisms include:
6. Salmonella typhi
7. Proteus sp.
8. Neisseria meningitidis 

 

Plasmids, Lysogeney, and Pathogenicity

 

1. Plasmids may carry genes for antibiotic resistance, toxins, capsules and fimbriae.
2. Lysogenic conversion can result in bacteria with virulence factors, such as toxins or capsules.

 

Pathogenic Properties of Nonbacterial Microorganisms

 

Viruses

 

1. Viruses avoid the host’s immune response by growing inside cells.
2. Viruses gain access to host cells because they have attachment sites for receptors on the host cell.
3. Visible signs of viral infections are called cytopathic effects (CPE).
4. Some viruses cause cytocidal effects (cell death), and others cause noncytocidal effects (damage but not death).
5. Cytopathic effects include the stopping of mitosis, lysis, the formation of inclusion bodies, cell fusion, antigenic changes, chromosomal changes, and transformation.

 

Fungi, Protozoa, Helminths and Algae

 

1. Fungal infections cause damage by:
1. Capsules
2. Toxins
3. Allergic responses
2. Protozoan and helminths cause damage to host tissue by:
1. Direct cell damage
2. Metabolic waste products
3. Blocking lymph flow
4. Taking nutrients
5. Allergic reactions
6. Some protozoa change their surface antigens while growing in a host so that the host’s antibodies don’t kill the protozoa.
3. Some algae produce neurotoxins that cause paralysis when ingested by humans.