4th exam part 5

Virulence Factors - Toxins

• Virulence factors include adhesions, exoenzymes (some act as toxins), exotoxins, and metabolic pathways.
• Exotoxins are synthesized by specific bacteria, including toxin genes found on plasmids or prophages.
• Exotoxins are among the most lethal substances known, with a small LD50.
• Exotoxins are highly immunogenic, stimulating the production of neutralizing antibodies (antitoxins).
• Exotoxins can be inactivated to form toxoids, and passive immunity in the form of antitoxin can be used for treatment.
• Exotoxins can be grouped into functional categories, such as neurotoxins, causing nervous system damage and paralysis, tissue-specific enterotoxins (damaging intestines and digestive tract tissues), and cytotoxins, damaging various cells and tissues.
• Exotoxins are released extracellularly and can travel far from the infection site.
• Cytolytic toxins attack cell components causing lysis, while A-B toxins (with a binding subunit 'B' and a toxic 'A' subunit) are site-specific and can disrupt membranes.
• Superantigen toxins stimulate a large immune response and subsequent inflammation.

Cytolytic Toxins

• Two main types of cytolytic toxins are lipases and phospholipases (lecithinases).
• Pore-forming toxins like leucocidins and streptolysins create pores in cell membranes.
• Other cytolytic toxins, such as phospholipases, remove polar heads from phospholipids, destabilizing the membrane, and causing cell lysis.
• An example is Clostridium perfringens.

Pore-forming Exotoxins

• Leukocidins kill phagocytic leukocytes.
• Hemolysins kill erythrocytes, leukocytes, and other cells.
• Examples include streptolysin-O (SLO) and streptolysin-S (SLS), with SLO being oxygen-sensitive and SLS being oxygen-stable.
• Staphylococcus aureus produces an example of a pore-forming toxin.

A-B Toxins

• A-B toxins are composed of two parts: A and B subunits.
• The B subunit binds to specific host cell receptors, facilitating entry.
• The A subunit is the toxic or active part.
• The structure of A-B toxins offer novel approaches for vaccine and therapy, as their structure can be used for binding and delivery systems.
• Ex: Diphtheria toxin (Corynebacterium diphtheriae) inhibits protein synthesis by preventing tRNA binding to ribosomes. Rats/mice are resistant, but humans are susceptible to the toxin.
• Other A-B toxins such as tetanus toxin and botulinum toxin are produced from Clostridium bacteria. Botulism toxin prevents muscle contraction while tetanus toxin prevents muscle relaxation.

Superantigen Toxins

• Superantigens elicit a very strong immune response by inducing the extensive release of cytokines.
• This leads to a systematic inflammatory response, resulting in symptoms like vomiting, diarrhea, and fever.
• Superantigens can also contribute to autoimmune diseases.
• Examples include Toxic Shock Syndrome Toxin (TSST-1), staphylococcal and streptococcal toxins, staphylococcal enterotoxin A (produced by Staphylococcus aureus), scarlet fever toxin (produced by Streptococcus pyogenes).

Immune Responses

• Immune responses can be damaging, with antigen-antibody complexes settling in joints and kidneys causing destructive inflammation.
• Cross-reactive antibodies bind to the body's own tissues, promoting autoimmune responses.
• Streptococcus pyogenes can cause rheumatoid arthritis as an example.

Endotoxins

• Endotoxins are components of gram-negative bacteria (LPS, Lipid A).
• They are released when gram-negative cells are lysed, and they are heat-stable.
• Endotoxin symptoms include fever resulting from pyrogen release, diarrhea, and inflammation.
• They are not suitable for use as toxoids.
• Endotoxins play a significant role in septic shock.

How Endotoxins Compare to Exotoxins

• Endotoxins are less toxic than exotoxins, with much higher LD50 amounts.
• Endotoxins can still contribute to clinical problems, and their presence can significantly increase the sensitivity to other toxins, such as TSS toxins,
• The presence of endotoxin can increase sensitivity to TSS toxins up to a million-fold.

Limulus Test

• Limulus amebocyte lysate (LAL) is used as a presumptive test for endotoxin. This test uses amoebocytes from horseshoe crabs.
• The blood or lysate clots in response to endotoxins.

Endotoxemia

• Endotoxemia is often associated with bacterial infections and severe wounds with high significance in intensive care units.

Problems with Limulus Test

• The Limulus test can't discriminate between live or dead cells, or toxin types of different species.

Additional Questions

• Endotoxin definition, bacterial source, symptoms, and assay methods are addressed in the text.
• This text notes that next time, diseases will be discussed.

Explore the critical role of virulence factors, focusing on exotoxins and their interaction with host systems. This quiz will test your knowledge about toxins, their effects, types, and treatment options. Understand how exotoxins contribute to bacterial pathogenicity and the immune response they elicit.