answer from the powerpoint

Chapter 7

Concepts of Microbial Disease

Public Health 4030

8/31/2017 1Ch. 07 - Microbial Disease

Biological Associations

• Symbiosis or “living together,” is an association between two or more species

8/31/2017 2Ch. 07 - Microbial Disease

Symbiosis • Mutualism – a condition in which both species

benefit (lichens)

• Commensalism, one species benefits but the other neither benefits nor is harmed (normal flora)

• Parasitism, is an association in which the parasite lives at the expense of the other species, the host (all microbial pathogens)

Lichens – Fungus and an alga or cyanobacterium

Termites and protozoa

8/31/2017 3Ch. 07 - Microbial Disease

The human

normal flora is

composed

mainly of

commensal

bacteria

Figure 07.04: The normal flora: mostly commensal organisms.

• E. coli in our gut: produces vitamin K2 (menaquinone )–fat soluble needed for host protein posttranslational modification. • Needed for Blood coagulation, bone health (calcification)

8/31/2017 4Ch. 07 - Microbial Disease

There is a see-saw relationship between

mutualism, commensalism, and parasitism

Figure 07.05: The slippery see-saw of symbiosis—from mutualism to parasitism.

8/31/2017 5Ch. 07 - Microbial Disease

The normal flora can be opportunistic pathogens.

• Individuals with HIV are more prone to be infected with….

– Candidiasis (Thrush)

– Cytomegalovirus – virus that can cause eye disease

– Herpes simplex virus (oral and genital herpes)

– Mycobacterium avium complex

– Pneumocystis pneumonia – fungal infection

– Toxoplasmosis – protozoal infection of brain

– Tuberculosis – bacterial infection

8/31/2017 6Ch. 07 - Microbial Disease

Parasitism: A Way of Life

• Parasites are the cause of infectious disease

– live at the expense of the host

– cause damage to the host

• Parasitism results in a constant negotiation between the parasite and the host, as each evolves in response to the other

– Does disease presentation mean microbe has crossed the line from being commensal?

– How do we determine what is parasitism?

8/31/2017 7Ch. 07 - Microbial Disease

Koch’s Postulates 1. Association: The causative agent must be present in

every case of a specific disease.

2. Isolation: The causative agent must be isolated in every case of the disease and grown in pure culture.

3. Causation: The causative agent in the pure culture must cause the disease when inoculated into a healthy and susceptible laboratory animal.

4. Reisolation: The causative agent must be reisolated from the laboratory animal and be identical to the original causative agent.

8/31/2017 8Ch. 07 - Microbial Disease

Koch’s postulates: association, isolation, causation, and reisolation, are still used to establish the cause of infection.

Figure 07.07: Koch’s postulates.

8/31/2017 9Ch. 07 - Microbial Disease

Microbial Mechanisms of Disease

• The chance of acquiring an infection depends

upon three major factors:

– (n) dose, the number of microbes encountered

– (V) virulence, virulence factors

– (R) resistance, host immunity

• Severity of infection = D = nV/R

8/31/2017 10Ch. 07 - Microbial Disease

Pathogenicity and Virulence

• Infective dose (ID), minimal number of microbes necessary for infection – More virulent organisms have smaller IDs than less

virulent organisms • Vibrio cholerae (causes cholera) ID = one million

• Mycobacterium tuberculosis (causes TB) ID = 10

• LD50 is the number

of microbes necessary

to kill 50% of the animals

infected

Figure 07.08: An LD50 dose-

response curve.

8/31/2017 11Ch. 07 - Microbial Disease

8/31/2017 Ch. 07 - Microbial Disease 12

ID50 = 50% infective dose

LD50 = 50% lethal dose

minimum dose to establish 50% infection

Mycobacterium tuberculosis (TB)

Vibrio cholera (cholera)

e.g.

106

10

ID50

Virulence: depends on pathogen dose (n)

D = nV/R D = disease severity

n = dose (number of pathogens) V = virulence (pathogen)

R = resistance (host)

Highly virulent means what to infective dose????8/31/2017 13Ch. 07 - Microbial Disease

8/31/2017 Ch. 07 - Microbial Disease 14

http://www.cnn.com/2016/09/02/health/fda-bans-antibacterial-soap/index.html

Characteristics of Infectious Disease Agents

• Infectivity – The capacity of an agent to produce infection or

disease.

– What about subclinical or asymptomatic infections?

• Pathogenicity – The capacity of the agent to cause disease in the

infected host.

– Measured by the proportion of individuals with clinically apparent disease.

8/31/2017 15Ch. 07 - Microbial Disease

Characteristics of Infectious Disease Agents

• Virulence

– Refers to the severity of the disease.

– Measured by the proportion of total cases with overt infection divided by the total number of infected cases. If fatal, use case fatality rate.

• Toxigenicity

– The capacity of the agent to produce a toxin or poison. (e.g. Clostridium botulinum)

8/31/2017 16Ch. 07 - Microbial Disease

Pathogenicity and Virulence (cont.)

• Pathogenicity is the ability to cause disease

• Virulence is a measure of pathogenicity, it

encompasses two types of virulence factor:

– Defensive strategies that allow microbes to escape

destruction by the host immune system (adhesins,

capsules, antigenic variation, etc.)

• Why do pathogens need defensive strategies?

– Offensive strategies that result in damage to the

host (exoenzymes, exotoxins, endotoxins, etc.)

• Why do pathogens need offensive strategies?

8/31/2017 17Ch. 07 - Microbial Disease

Table 07.01: Bacterial Mechanisms Of Virulence.

8/31/2017 18Ch. 07 - Microbial Disease

Adhesins enable adherence of

pathogens to cell receptors at a portal

of entry.

• Where would Neisseria gonorrhoeae need to adhere? • Why would it need to adhere?

• Where would Lactobacillus adhere?

• HIV?

• Salmonella?

• Treponema pallidum? (STD)

• Giardia?

8/31/2017 19Ch. 07 - Microbial Disease

Removal of the capsule from encapsulated bacteria

makes them more susceptible to phagocytosis

Figure 07.10: Capsules and phagocytosis.

8/31/2017 20Ch. 07 - Microbial Disease

2) M protein

Streptococcus pyogenes

3) “waxy coat”

Mycobacterium tuberculosis (TB)

necrotizing fasciitis

defensive virulence strategies:

8/31/2017 21Ch. 07 - Microbial Disease

Antigenic variation: trypanosomes can change

surface antigens to avoid host antibodies.

African sleeping sicknessTsetse fly 8/31/2017 22Ch. 07 - Microbial Disease

Defensive strategies (cont.)

Helicobacter pylori, the bacterium

that causes peptic ulcers, secretes the

enzyme urease, which enables it to

survive in the highly acidic

environment of the stomach

Figure 07.12: Location and progression of gastric ulcers.

Offensive Strategies: Exoenzymes

• Enzymes are proteins with activities that allow the invading bacteria to spread throughout the tissues, causing damage in the process.

• Examples… – Hyaluronidase breaks down hyaluronic acid content

of connective tissues – Collagenase breaks down collagen which can result in

necrotic (dead) tissue that requires debridement – Hemolysins destroys red blood cells – Kinases break down clots – Leukocidins destroy white blood cells

8/31/2017 24Ch. 07 - Microbial Disease

Offensive Strategies: Toxins

• Endotoxin is part of the Lipopolysaccharide in the outer membrane of gram-negative cells – It causes shock, chills, fever, weakness, small blood

clots, and, possibly, death

• Exotoxins are proteins synthesized by the microbe and secreted into the host’s tissues – Cytotoxins, kill or damage cells

– Neurotoxins, block nerve impulse transmission

– Enterotoxins, affect cells lining gastrointestinal tract

• Toxoid, detoxified toxin, retains its antigenicity

8/31/2017 25Ch. 07 - Microbial Disease

Table 07.03: Characteristics of Bacterial Exotoxins and Endotoxins.

8/31/2017 26Ch. 07 - Microbial Disease

Botulinum toxin causes a flaccid muscle paralysis,

while tetanus toxin works in the reverse.

Figure 07.14: Activity of botulinum and tetanus toxins.

8/31/2017 27Ch. 07 - Microbial Disease

Table 07.02: Diseases Manifested by Exotoxins.

8/31/2017 28Ch. 07 - Microbial Disease

Virulence Mechanisms of Nonbacterial Pathogens

• Viruses – Defensive: antigenic variation

(influenza – new vaccine every year)

– Offensive: death (lysis) of host cell from

– Production of large numbers of replicating viruses

– Inhibiting host protein synthesis

– Damage to plasma membrane

– Inhibiting host cell metabolism

• Eukaryotic Microbes (including helminths) – Combination of offensive and

defensive strategies described for bacteria (adhesins, toxins, antigenic variation, etc.)

8/31/2017 29Ch. 07 - Microbial Disease

Table 07.04: Stages of Microbial Disease.

8/31/2017 30Ch. 07 - Microbial Disease