Chapter 17 Host- Microbe Interaction Biology 261 Medgar Evers College, CUNY Prof. Santos

Establishing cause of infectious disease 1- Koch’s postulate a- the microorganism must be present in every case of the disease b- the organism must be grown in pure culture from dispersed hosts. c- the same disease must be produced when a pure culture of the organism is introduced into a host. d- the organism must be removed or isolated from experimentally infected hosts.

Molecular Koch’s postulates a- the virulence factor or its product should be found in pathogenic strains of the organism. b- mutating the virulence gene to disrupt its function should reduce the virulence of the pathogen. c- reversion of a mutated virulence gene or replacement with a wild type version should restore virulence to the strain.

Pathogenicity Pathogenicity refers to the ability of an organism to cause disease (harm the host). This ability represents a genetic component of the pathogen and the overt damage done to the host is a property of the host-pathogen interactions.

Virulence The extend of pathogenicity

Mechanism of pathogenicity 1- establishment of infection 2- invasion and breach of anatomical barriers 3-avoiding host defense 4-damage to the host

Establishment of infection Adherence- the use of adhesin proteins to bind to host. Adhesin proteins are found at tip of pili. Pili used for attachment are called fimbriae. The binding of an adhesin to host surface receptor is highly specific.

Colonization Colonization- this involves taking over site that is already populated by a normal flora. The pathogen must compete for nutrients, space, and overcome the host’s immune system. Ig A antibodies circulating the host bind to adhesin proteins of pathogen preventing their attachment to host receptor. To overcome this, a rapid turnover of the pili occurs, antigenic variation of the pili can occur and the activation of IgA protease to destroy IgA.

Invasion of Anatomical barriers I Penetration of skin to get in or get in by means of a vector such as an arthropod II Penetration of the mucous membrane by inducing mucosal epithelial cells to engulf the bacteria. Some pathogens exploit antigen sampling processes.

Antigenic sampling Special cells called M cells are located between the intestinal lumen and secondary lymphoid tissues called peyer’s patches. These M cells sample fluids of the intestine and if a microbe is detected, it delivers the microbe to a macrophage that destroys it. This kind of cell to cell delivery is called transcytosis.

Some strains of shigella exploit this system to get into the mucous membranes and induce apoptosis in the phagocyte.

Avoiding the host defense I Hiding inside the host II Avoiding killing by complement system proteins III Avoiding destruction by phagocytosis by avoiding recognition, attachment, and eventually escaping from the phagosome. IV Avoiding antibodies by using proteases to destroy them, antigenic variation, mimicking “self cells”.

Avoiding recognition 1- capsule proteins inactivate the C3b complement component 2- M proteins found in strains of Streptococcus pyogenes also inactivate the C3b complement component. 3- Fc receptors found on the surface of Staphylococcus and Streptococcus bind to the fc region of an antibody preventing it from binding correctly!

Damage to the host 3 main mechanisms; Release of exotoxins Use of endotoxins Damaging effect of the Immune system

Exotoxins These are proteins that have very specific damaging effects. There are 4 types; 1- A-B toxins, the A subunit is the toxin while the b subunit binds to specific receptors on target cell. 2- Super-antigens interfere with T cell responses by causing non-specific activation of T cells. This leads to a massive release of cytokines that can promote tissue damage.

Examples of AB toxins Cholera exotoxin Enterotoxins Pertussis toxin Anthrax toxin Botulin toxin Tetanus toxin Neutrophil activating protein

Examples of superantigens 1- Toxic shock syndrome toxin-1- secreted by S. aureus leading to fever, rash and shock 2- Staphylococcal enterotoxin- secreted by S.aureus leading to vomiting, fever, diarrhea, and nausea.

3- Membrane damaging toxins that disrupt the integrity of the cell membrane by forming pores or removing the polar head group on phospholipids 4-Hydrolytic enzymes that can break down tissues. Example is exfoliatin toxin secreted by S. aureus to cause scalded skin syndrome.

Endotoxin a toxin that is confined inside the microorganism and is released only when the microorganism is broken down or dies.

Endotoxins This involves the Lipid A of the LPS of a cell wall of a bacteria. The host immune system produces massive amounts of pro- inflammatory cytokines in response to its presence. The immune system will mount a massive attack against lipid A. This can lead to systemic shock or endotoxic shock.

Damaging effect of the immune system An over reaction of the host immune system can cause the release of enzymes and toxic products that can damage the tissues of the host. Antigen antibody complexes can cause kidney and joint damage and cross reactive antibodies can trigger autoimmune diseases.