1Host-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.

2Terms, 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

3Terms, 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.

4Where 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

5Where 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.

6What 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.

7How 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.

8Whether 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.

9Types 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

10Types 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”

11How 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.

12Disease 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

13Steps 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.

14Typical 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.

15Step 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.

16Virulence 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

17Hijacking 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