1 How bacteria cause disease Bacteria can be invasive –Bacteria spread through tissues, usually using digestive enzymes which damage tissues, kill cells. Bacteria can be toxigenic (produce toxins) –Bacteria may not spread, but release soluble toxins which dissolve in body fluids, damaging cells. –Gram negative contain endotoxin (LPS) Host processes –Host defenses, like inflammation, may over- respond, cause significant tissue damage.

2 Disease by other microbes How viruses causes disease –Viruses multiply inside host cells, using cell resources, often killing cells. –Viruses stimulate the immune system to fight back; infected cells are killed. –Viruses alter cell cycle regulation to promote their own replication; may lead to cancer. Fungi, Protists, and worms –Produce enzymes that damage host cells –Multiply in host cells and kill them –Cause allergic reactions or inflammation

3 Steps in an infectious disease-Overview Entry and attachment –Microbe needs to approach tissue, then attach to it. Deal with host defense –Successful parasite must infect, persist long enough to reproduce, then escape. Host defense seeks to kill it. Damage: if disease is involved, damage occurs. Escape: parasite must escape and spread to others. –Discussed in “Portals of exit” Virulence Factors: Things that bacteria have that improve their abilities to cause disease –Fimbriae, capsules, enzymes, toxins, all these things.

4 Virulence factors: enzymes and toxins Enzymes –Collagenase, hyaluronidase, coagulase, streptokinase. Allow spread or hiding of pathogen. Toxins –Exotoxins, produced by G+ and G-, proteins, heat labile, released and affect different targets Enterotoxins, neurotoxins, general cytotoxins. –Endotoxin: LPS, especially Lipid A part Present only on Gram – Released when bacterium dies –Acts as Super antigen

5 Hijacking host defenses Inflammation –A protective mechanism, but can cause local damage. Chronic inflammation results in loss of functional tissue, disease. Super antigens –Endotoxin, Toxic Shock Syndrome toxin, et al. Cause massive over response of WBS Fever, shock, intravascular coagulation

6 Epidemiology Epidemiology is the study of disease: –the study of the factors involved in the frequency and spread of disease. Incidence: # of new cases during a time period Prevalence: ongoing cases at any one time Mortality and morbidity rate: –Death and sickness per total population over a given period of time. –Many diseases have unique patterns, such as flu occurring during the winter months.

7 The first epidemiological study John Snow, London, 1854 The cause of cholera wasn’t known, but Snow guessed it was spread by water. By mapping all the known cases and comparing them to the sources of water, he correctly identified the source of the problem.

8 Where germs live: reservoirs Humans –May be sick, may be carriers Animals –Many diseases are zoonotic but can also be caught by humans; animal may be healthy or not. Non-living –Soil, water are typical homes to microbes that can cause disease.

9 The Ins and Outs of infections: Portals of entry and exit The successful parasite has to get in, multiply, then get out to spread to others. People have lots of entry points –Glands, follicles that open to outside –Larger openings: respiratory system, digestive system, genito-urinary tract –Cuts, bites, burns, surgical incisions –Crossing the placenta, infecting the fetus Pathogens have favored portals of entry –Some microbes aren’t harmful if portal is not optimal

10 Exit The portal of exit is often the same or connected to a portal of entry –Coughing sneezing speaking: from mouth –Excretory systems: GI tract, in feces; in urine –From sex: vaginal fluid, semen –From blood: insect bites, shared needles ito.jpg

11 Transmission Microbe needs to get from reservoir to you. Contact –Direct contact: touching, kissing, sex, endogenous spread (one part of you to another) –“vertical”: mother to offspring, e.g. transovarian –Indirect contact, via fomites (inanimate objects) –Droplet transmission: less than 1 meter thru air /sneeze.jpg

12 Transmission-2 Vehicles –Water: various viruses, bacteria, protozoa, mostly that cause diarrhea and enter water supply. –Food: unpasteurized or contaminated food, either improperly grown, processed, or prepared. –Airborne: microbes attached to dust, skin flakes, dried mucus become aerosols, travel thru air.

13 Transmission-3 Vectors –Typically arthropods (insects, ticks) –Mechanical vectors: simply spread disease, e.g. houseflies walking on feces, spread germs to humans. –Biological: pathogen goes through part of life cycle in vector Viruses or protozoa that reproduce within mosquito, e.g. Major method for spread of zoonoses.

14 Susceptibility and transmission Exogenous vs. endogenous –Exogenous means infection comes from outside the host. Examples: common cold, STD. –Endogenous means host is original source of infection. Examples: boils on skin spread by fingers from Staph sinus infection; E. coli urinary tract infection. Compromised host –Weakened immune system, poor lung clearance from bed rest, surgical wounds, bedsores, etc.

15 Koch’s Postulates Historical context: –So many germs, so many diseases –Logical framework for matching them Microbe must be found in every instance of the disease. Obtain microbe in pure culture Produce disease in susceptible host Re-isolate original microbe