1. 1 Host-Microbe Relationships and Disease Classical ecological definitions –Mutualism: organisms live together, both benefit E. coli in GI tract; we get Vitamin K, protection from pathogens, it gets warm wet place to live, lots to eat. –Commensalism: one organism benefits, the other is not particularly benefited or harmed; to eat at the same table Most GI tract microbes; we provide a warm wet place to live with food, we don’t get all that much in return. –Parasitism: one organism benefits at the other’s expense Disease-causing bacteria; to them, we’re dinner. Classically, a “parasite” lives in or on host.

2. 2 Terms, terms, and more terms Contamination: presence of microbes (where they don’t belong). Infection: multiplication of parasitic organisms in/on host. –Infestation: used to describe larger organisms, e.g. lice. Disease: malfunction in or damage to the host. –Many kinds of “disease”; here we discuss “infectious disease”. –Disease is a condition of the host, not an infectious microbe. Pathogen: a parasite capable of causing disease –Not all pathogens are equal as we will see.. Pathogenicity: ability of pathogen to cause disease

3. 3 Terms, terms, and more terms-2 Virulence: relative ability to cause disease. –Especially variations in pathogenicity w/in specific group –Can be weakened (attenuation) or increased (animal passage); Growing pathogens on agar attenuates them. Normal microbiota: the microbes normally found on the body. Since people are not “normally” sick, pathogens are not normally consider “normal microbiota”. “flora” is to be avoided as microbes are NOT plants! –Resident microbiota: always found on human tissues. –Transient microbiota: come and go, can include potential pathogens.

4. 4 Where do they live? Microbes live where it is “topologically outside” –We are a tube within a tube. We have sacs open to the outside. Respiratory tract: –nasal passages, sinuses, trachea, lungs. Lungs well protected, other areas more populated. GI tract: Crowded! –Mouth is full, fewer in esophagus and stomach; toward end of small intestine, numbers increase greatly. –Feces consist largely of bacteria. http://www.radiation-scott.org/deposition/respfig2.gif

5. 5 Where do they live?-2 Skin: largest organ in the body. –Colonized. Various factors keep the numbers down. Genito-urinary tract: –Female reproductive tract colonized, especially with Lactobacillus (helpful) and yeast (sometimes harmful) –Lower portion of urethra contains some bacteria, but bladder, ureters, and kidneys normally sterile. Fluids –Blood, cerebrospinal fluid should be sterile All areas of the body have mechanisms for keeping us from being lunch; to be discussed soon.

6. 6 What determines whether we get sick? Inf Dis: the likelihood of contracting an infectious disease. N: the numbers of infecting organisms. V: the virulence of the organism. HF: host factors, including overall health, nutritional status, genetic background, age, immune status.

7. 7 How dangerous? Pathogen: causes disease. Opportunistic pathogen: can cause disease under the right circumstances –Dose in high numbers –Host is in a weakened state, e.g. HIV infection. –Organism gets where it doesn’t belong E. coli and urinary tract infections. –Lack of microbial antagonism, e.g. superinfection competition for space, nutrients; bacteriocins. Saprotroph: decompose dead stuff.

8. 8 Whether an organism will cause disease is not always a clear cut thing Not everything in biology can be neatly classified. There is a gradation from pathogen to opportunist to non-infectious, and what happens depends on the balance of these 3 factors.

9. 9 Types of disease Inherited diseases: caused by a faulty gene Congenital: due to damage during development. Degenerative diseases, due to age or lifestyle Nutritional, endocrine, mental, immunological, neoplastic (cancer), idiopathic; same caveat. Iatrogenic: caused by doctor. –Nosocomial infections: occur in hospital. Infectious disease: caused by infectious agents –Bacteria, viruses, fungi, etc. –Infectious agents may affect other types of disease

10. 10 Types of infectious diseases Communicable: can be spread from one person to another. –Example: tuberculosis, HIV Contagious: highly communicable, can easily be spread from one person to another. –Genital herpes, measles. Non-communicable: are not spread from one host to another. –Examples: your infected appendix bursts –You get tetanus from “rusty nail”

11. 11 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.

12. 12 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

13. 13 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.

14. 14 Typical steps in a bacterial infection Attachment –Typical first step is attachment to tissues. Often a specific interaction takes place between molecules. –Fimbriae, capsules help in attachment. –Molecules that aid in attachment = adhesins. Deal with host defenses –A pathogen can defend, attack, or hide. Interfere with phagocytosis, have a capsule, etc. Produce leukocidins, etc. Switch surface antigens, hide inside WBC, etc.

15. 15 Step 3: Damage Damage occurs from combination of factors –Bacteria increase their growth by Releasing enzymes that break down host cell molecules, releasing nutrients or allowing spread. –Hemolysins release iron; siderophores collect. Releasing toxins that kill cells or damage organ systems, eliminating host resistance. –Bacteria cause disease by Stimulating inflammation, leading to damage and discomfort Over-stimulating host defense, damaging cells and organ systems.

16. 16 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

17. 17 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 –Followed by decreased responsiveness Fever, shock, intravascular coagulation