Chapter 14 Add-on

How Bacterial Cells Damage Host CellsThree mechanisms:

• Direct Damage• Toxins*• Hypersensitivity Reactions

* Most bacterial damage is carried out by toxins.

1. Direct Damage Some bacteria can induce cells to engulf them (E.

coli, Shigella, Salmonella, and Neisseria gonorrhoeae).

Microbial metabolism and multiplication kills host cells.

Other microbes enter the cell by excreting enzymes or through their own motility.

2. Toxin Production Toxins: Poisonous substances produced by

microbes. Frequently toxins are the main pathogenic factor. Toxigenicity: Ability of a microbe to produce

toxins. Toxemia: Presence of toxins in the blood. Toxin effects: May include fever, cardiovascular

problems, diarrhea, shock, destruction of red blood cells and blood vessels, and nervous system disruptions.

Of 220 known bacterial toxins, 40% damage eucaryotic cell membranes.

Two types of toxins: • Exotoxins• Endotoxins

A. Exotoxins• Proteins: Enzymes that carry out specific

reactions. • Soluble in body fluids, rapidly transported

throughout body in blood or lymph.• Produced mainly by gram-positive bacteria.• Most genes for toxins are carried on plasmids or

phages.• Produced inside bacteria and released into host

tissue.• Responsible for disease symptoms and/or death.

Cytotoxins: Kill or damage host cells.Neurotoxins: Interfere with nerve impulses.Enterotoxins: Affect lining of gastrointestinal

tract.• Antibodies called antitoxins provide immunity.• Toxoids: Toxins that have been altered by heat or

chemicals. Used as vaccines for diphtheria and tetanus.

Important ExotoxinsDiphtheria Toxin: Corynebacterium diphtheriae when

infected by a phage carrying tox gene. Cytotoxin inhibits protein synthesis in eucaryotic cells. Two polypeptides: A (active) and B (binding).

Erythrogenic Toxins: Streptococcus pyogenes produces three cytotoxins which damage blood capillaries, causing a red rash.

Botulinum Toxins: Produced by Clostridium botulinum. Neurotoxin that inhibits release of neurotransmitter acetylcholine and prevents transmission of nerve impulses to muscles, causing flaccid paralysis. Extremely potent toxins.

Tetanus Toxin: Produced by Clostridium tetani. A neurotoxin that blocks relaxation of skeletal muscles, causing uncontrollable muscle spasms (lockjaw) and convulsions.

Vibrio Enterotoxin: Produced by Vibrio cholerae. Two polypeptides: A (active) and B (binding). The A subunit of enterotoxin causes epithelial cells to discharge large amounts of fluids and electrolytes.

Staphylococcal Enterotoxin: Staphylococcus aureus produces an enterotoxin similar to cholera toxin. Other enterotoxins cause toxic shock syndrome.

Neonatal Tetanus (Wrinkled brow and risus sardonicus)Source: Color Guide to Infectious Diseases, 1992

Muscle Spasms of Tetanus are Caused by Neurotoxin of

Clostridium tetani

Rice-water stool of cholera. The A subunit of enterotoxin causesepithelial cells to discharge large amounts of fluids and electrolytes.Source: Tropical Medicine and Parasitology, 1995

Vibrio Enterotoxin Causes Profuse Watery Diarrhea

Scalded Skin Syndrome Toxic Shock Syndrome

Endotoxins• Part of outer membrane surrounding gram-

negative bacteria.• Endotoxin is lipid portion of

lipopolysaccharides (LPS), called lipid A.• Effect exerted when gram-negative cells

die and cell walls undergo lysis, liberating endotoxin.

• All produce the same signs and symptoms: Chills, fever, weakness, general aches, blood clotting and tissue death, shock, and even death. Can also induce miscarriage.

Fever: Pyrogenic response is caused by endotoxins.

Endotoxins (Continued)• Endotoxins do not promote the formation of effective antibodies.

• Organisms that produce endotoxins include: Salmonella typhi Proteus spp. Pseudomonas spp. Neisseria spp.

• Medical equipment that has been sterilized may still contain endotoxins. Limulus amoebocyte assay (LAL) is a test used to detect tiny amounts of endotoxin.