Host-Microbe Interactions

Numbers The total number of microbes that

colonize the surface of an adult body is 10 times greater than the total number of human cells

Human genome encodes for 223 proteins with significant homology to bacterial but not eukaryotic proteins

Symbiosis: Relation between 2 different species

Mutualism: both partners benefit

Commensalism: one partner benefits, other is unharmed

Parasitism: one organism benefits at expense of other

Symbiotic Associations

Examples

Cleaner Shrimp/Zebra Moray Eel

Mutualism

Examples

Oxpecker bird /Rhinoceros

Mutualism

Examples

Parasitism

Braconid wasp/ Tomato hornworm

Firmicutes/ Human skin

Comensalism

Examples

Examples

Mycorrhizae/Plants

Mutualism

Examples

Commensalism

Escherichia /Human intestine

The Normal Microbiota

Resident microbiota

Transient microbiota

Why?How?

Why? Metabolic rate

Gastrointestinal function

Specific and quantitative aspects of immune function

Biochemical homeostasis

Influence on host–parasite relationships

Metabolic Rate

Carbohydrates and Complex Lipids

Vitamins: Biotin, Folate

Ions: Mg2+, Ca2+, Fe3+

Gastrointestinal Function

Immune Function Gut mucosa. Lacking normal microbiota leads to

smaller Peyers Patches, lower intraepithelial lymphocytes and lower secretion of IgA

Regulate the expression of the TLRs: differentiate pathogens and commensals

Allergies: Presence of certain bacteria stimulates the

T cells. Some microorganism are also responsible for the development of dendritic cells. Overall problem is no block of IgE production

The Present and the Future..

Damage to the HostDirect or Indirect

Toxins

Anthrax

Botulinum

Shiga

Proteins

Lipopolysaccharides

Direct

Damage to the HostIndirect

• Associated to Inflammation

Neisseria gonorrhoeae

• Associated to Adaptive Immunity

Glomerulonephritis

Rheumatic fever

Exotoxins

Endotoxins

Toxins• Soluble

Proteins/Polypeptides• Usually secreted by

bacteria• Act on site or at site

removed from bacterial growth• Gram (+) and Gram (-)

• Cell associated substances• Structural components of

bacteria• Location: Outer membrane

Gram (-)• Released from growing bacteria

or lysis/ effect of an atibiotic

Exotoxins (A/B Toxins)

A: TOXIC

B: Binds to surface

Attachment and Entry A) Direct : Formation of a pore

Geny B, 2006, Biol Cell

Attachment and Entry A) Receptor-Mediator Endocytosis

Exotoxins are proteins….

•Heat / Acid labile•Proteolytic enzymes•Catalysis (High biological activity)•Specificity• The host can generate antibodies against them: production of toxoids and antitoxins

What are some characteristics of enzymes that the host can take advantage to avoid their

detrimental effect?

Where? •Neurotoxins

•Enterotoxins

•Cytotoxins

Membrane-damaging toxins •Hemolysins : Form pores Avoid phagocytosis

•Phospholypases: Hydrolize phopholipids

Superantigens

Endotoxins• Lipopolysaccharide• Integral part of the outer membrane Gram (-)• No efficient toxoids

Structure of LPS

• Phosphorylated N-acetylglucosamine (NAG) dimer with 6 or 7 fatty acids (FA) attached. • All FA in Lipid A are saturated. Some FA are attached directly to the NAG dimer and others are esterified to the 3-hydroxy fatty acids that are characteristically present.

Mechanism1. Production of cytokines. IL and TNF activates macrophages to enhanced phagocytosis and cytotoxicity. 2. Activation of the complement cascade. C3a and C5a cause histamine release (leading to vasodilation) and affect neutrophil chemotaxis and accumulation.

3. Activation of the coagulation cascade.  Initial activation of Hageman factor (blood-clotting Factor XII)  can activate several humoral systems :a. coagulation: Leads to internal bleedingb. activation of the complement alternative pathway c. plasmin activation which leads to fibrinolysis and hemorrhaging. d. kinin activation releases bradykinins and other vasoactive peptides which causes hypotension.