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Prescott’s Microbiology, 9th Edition
35
Pathogenicity and Infection
CHAPTER OVERVIEW
This chapter focuses on infection and pathogenicity. The development of a disease state is a dynamic process
that is dependent on the virulence of the pathogen and the resistance of the host. This dynamic process is
illustrated in the discussions of viral and bacterial pathogenesis. Modes of transmission and development of
diseased states are presented. The chapter includes a discussion of mechanisms used by viruses and bacteria
to evade host defenses.
LEARNING OUTCOMES
After reading this chapter you should be able to:
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compare and contrast competition between microbial species with competition between microbial and
human cells
predict the microbial virulence factors and host cell responses that result in disease
relate the infectious disease process to time, identifying events associated with each stage of the process
identify and describe the features that allow microorganisms to overcome host resistance and immunity
discuss the strategies microorganisms have evolved to exploit human cells and tissues as resources for
their survival
compare the molecular mechanisms by which microorganisms adhere to and invade human cells and
tissues
illustrate the mechanisms by which microbial toxins impact human cells
model disease processes and explain virulence
list and describe the means by which microorganisms access humans to cause disease
correlate initial microbial numbers and replication rates to infection and lethality
synthesize a concept map of the infectious process
CHAPTER OUTLINE
I.
Pathogenicity and Infectious Disease
A. A parasitic organism is one that lives at expense of its host; any organism that causes disease is a
parasite
B. Infection—the state occurring when a parasite is growing and multiplying on or within a host
1. Infectious disease—a change from a state of health as a result of an infection by a parasitic
organism
2. Pathogen—any parasitic organism that produces an infectious disease
3. Pathogenicity—the ability of a parasitic organism to cause a disease
4. Primary pathogen—organism that causes disease in a healthy host by direct interaction
5. Opportunistic pathogen—organism that is normally free-living or part of the host’s normal
microbiota, but adopts a pathogenic role under certain circumstances (host weakness)
6. Fundamentally an infection is a competition for resources between pathogen and host.
C. Chain of Infection – a process where an agent gains access to the host
1.
Contact with agent
2.
Virulence of agent
3.
Method of exposure to agent –portal of infection
4.
Dose of agent present
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Prescott’s Microbiology, 9th Edition
II.
5.
Susceptibility of the host
6.
Exit of agent to new host
D. The final outcome of most host-parasite relationships is dependent on three main factors:
1. The number of pathogenic organisms present
2. The virulence of the organism
3. The host’s defenses or degree of resistance
E. Virulence—the degree or intensity of pathogenicity of an organism
F. Contacts with microbial agents
1. Reservoir - natural environmental location where pathogen normally resides
2. Zoonoses – pathogens that can be transmitted from animals to humans
3. Vectors- organisms that spread disease from host to anaother (eg. Deer ticks –Lyme disease)
Virulence
A. Virulence is the magnitude of harm (pathogenicity) caused by a particular microorganism; intrinsic
characteristics that contribute to pathogenicity are called virulence factors
B. Pathogenicity islands
1.
Large segments of DNA that carry virulence genes acquired during evolution by horizontal
gene transfer; are not present in nonpathogenic members of same genus or species
2.
Have unique sequence characteristics including several open reading frames with putative
genes, a different G + C content than the host, and insertion-like elements at their ends
C. Virulence factors
1. Adherence and colonization
a. Bacterium must be able to adhere to and colonize (but not necessarily invade) host cells
and tissue
b. Depends on ability of bacterium to successfully adhere to host and compete with normal
microbiota for essential nutrients
c. Adherence structures such as pili, fimbriae, and specialized adhesion molecules that
facilitate attachment to host cell receptors are important virulence factors
2. Invasion factors
a. Infectivity—ability of an organism to establish a focal point of infection
b. Invasiveness—ability of an organisms to spread to other tissues
c. Penetration of the host’s epithelial cells or tissues
1) Pathogen-associated mechanisms involve the production of lytic substances that:
(i) Attack the ground substance and basement membranes of integuments and
intestinal linings
(ii) Degrade carbohydrate-protein complexes between cells or on cell surfaces
(iii) Disrupt cell surfaces
2) Passive mechanisms of entry involve:
(i) Breaks, lesions, or ulcers in the mucous membranes
(ii) Wounds, abrasions, or burns on the skin surface
(iii) Arthropod vectors that penetrate when feeding
(iv) Tissue damage caused by other organisms
d. Invasion of deeper tissues can be accomplished by production of specific products or
enzymes that promote spreading (these are one type of virulence factor) or by entry into
the circulatory system; presence of bacteria in the blood is bacteremia; septicemia is
when toxins in the blood cause the disease process
3. Exotoxins – soluble proteins leaked into surrounding tissues
a. Heat labile
b. Generally associated with Gram positive bacteria
c. Toxic in low concentrations and can often effect host at a remote site
d. Can be grouped into four types based on structure and physiological activities
1) AB toxins can be separated into two distinct portions: one that binds the host cell
and one that causes toxicity (e.g., diphtheria toxin—binds host cell surface receptor
by the B portion and is taken into the cell by the formation of clathrin-coated
vesicles; toxin is then cleaved, releasing A fragment, which enters cytosol; the A
fragment inhibits protein synthesis)
2) Specific host site exotoxins: neurotoxins damage nervous tissue (e.g., botulinum
toxin and tetanus toxin), enterotoxins damage the small intestine (e.g., cholera
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© 2014 by McGraw-Hill Education. This is proprietary material solely for authorized instructor use. Not authorized for sale or distribution in any
manner. This document may not be copied, scanned, duplicated, forwarded, distributed, or posted on a website, in whole or part.
Prescott’s Microbiology, 9th Edition
toxin), and cytotoxins do general tissue damage (e.g., shiga toxin); some host-sitespecific exotoxins are also AB toxins (e.g., cholera toxin)
3) Membrane-disrupting exotoxins—two subtypes, those that bind cholesterol in the
host cell membrane and then form a pore ( e.g., leukocidins and hemolysins) and
those that are phospholipases (e.g., gas gangrene-associated toxin)
4) Superantigens— a subset of pathogen exotoxin proteins (e.g., staphylococcal
enterotoxin) that provoke overreactions of the immune system such as massive
cytokine releases, causing endothelial cell damage, circulatory shock, and
multiorgan failure
4. Endotoxins – Fundamental component of the bacterium which can cause disease (eg. LPS
of Gram negative bacteria)
a. Temperature resistant
b. Released only when the microorganism lyses or divides
c. Usually capable of producing fever, septic shock, blood coagulation, weakness, diarrhea,
inflammation, intestinal hemorrhage, and/or fibrinolysis; many of these effects are
indirect and are mediated by host molecules and cells (e.g., macrophages, endogenous
pyrogens, host cytokines).
5. Mycotoxins – toxins produced by fungi
a. Secondary metabolites in fungi commonly found in food crops and water-damaged
buildings; include aflatoxin from Aspergillus (liver damage and cancer), satratoxins from
Stachybotrys (inhibit DNA, RNA, and protein synthesis), and ergot alkaloids from
Claviceps (hallucinogen)
6. Biofilms- Persistant and complex heterogenous communities of microbial organisms
a. Reservoirs of infection
b. Physiological differences from free-living organisms in terms of resistance
c. Evade antimicrobial attack and immune system antibodies to gain resistance
D. Resisting host defenses
1. Successful infection by a microorganism requires that it avoid host immunity
2. Some pathogens infect immune cells and diminish their function; others avoid phagocytosis
with mucoidy capsules or specialized surface proteins (frustrated phagocytosis)
3. In some cases, pathogens use strategies to prevent detection by antimicrobial proteins
4. Some microorganisms survive inside host cells or can escape from hosts and spread
5. Many pathogens avoid the immune system by changing surface antigens, producing
capsules that resemble the host, or producing enzymes that degrade host proteins that bind
bacteria
6. Biofilm communities bring microorganisms together enhancing nutrient acquisition, safety
from predators, and protection from the immune system and antibiotics
III. Exposure and Transmission
A. Exposure and Transmission
1. Airborne transmission—suspended in air; travels a meter or more
a. Droplet nuclei—may come from sneezing, coughing, or vocalization
b. Dust particles—may be important in airborne transmission because microorganisms
adhere readily to dust
2. Contact transmission—touching between source and host; direct (person to person)involves
physical interaction between infected person and host
3. Vehicle transmission—inanimate materials or objects are involved in transmission
a. Common vehicle transmission—a single vehicle serves to spread the pathogen to
multiple hosts, but does not support its reproduction
b. Fomites—common vehicles such as surgical instruments, bedding, eating utensils
c. Food and water also are common vehicles
4. Vector-borne transmission—living transmitters, such as arthropods or vertebrates
a. External (mechanical) transmission—passive carriage of the pathogen on the body of the
vector with no growth of the pathogen during transmission
b. Internal transmission—carried within the vector
1) Harborage—pathogen does not undergo morphological or physiological changes
within the vector
3
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manner. This document may not be copied, scanned, duplicated, forwarded, distributed, or posted on a website, in whole or part.
Prescott’s Microbiology, 9th Edition
2)
B.
C.
D.
E.
Biologic—pathogen undergoes morphological or physiological changes within the
vector
5. Vertical transmission – passage of a disease microorganism from mother to child
a. Babies born with such diseases are said to have a congenital infection.
b. Examples of organisms that have exploited this route: Gonorrhea, Herpes,
Rubella.
Infectious dose
1. Size of initial inoculum affects rate at which infection proceeds and its severity
2. Infectious dose 50 (ID50)—number of microorganisms required to cause clinical disease in
50% of inoculated hosts
Growth rate
1. Successful colonization requires favorable growth conditions
2. Intracellular parasites grow within host cells
a. Facultative intracellular parasites can grow within cells or the environment
b. Obligate intracellular parasites can only grow in host cells
Host susceptibility—depends on defense mechanisms of the host and the pathogenicity of the
pathogen
Exiting the host—must be able to leave host or disease cycle will be interrupted and the bacterium
will not be perpetuated
1. Active escape—movement of pathogen to portal of exit (e.g., many helminths
2. Passive escape—excretion in feces, urine, droplets, saliva, or desquamated cell
CRITICAL THINKING
1.
Compare and contrast exotoxins and endotoxins. Discuss the chemical and physiological characteristics
of the molecules, as well as their mechanisms of pathogenesis.
2.
Describe the different mechanisms by which pathogens can be transmitted. Which type of transmission
seems the most effective in causing large outbreaks? Pathogens transmitted by which mechanism might
be the most easily controlled and eliminated?
3.
Explain why some pathogens can be “opportunistic” unable to infect healthy individuals, but take
advantage when the immune system is compromised or other normal process are altered by disease.
4.
Propose some methods that may be employed to determine whether an infection is caused by a bacterial
pathogen or whether it is being caused by a virus.
CONCEPT MAPPING CHALLENGE
Construct a concept map using the following words and your own linking terms.
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© 2014 by McGraw-Hill Education. This is proprietary material solely for authorized instructor use. Not authorized for sale or distribution in any
manner. This document may not be copied, scanned, duplicated, forwarded, distributed, or posted on a website, in whole or part.
Prescott’s Microbiology, 9th Edition
Infection Mycotoxins Carrier Zoonoses Source
LPS Exit Airborne Vector Contact Endotoxin
of infection Hemolysis
Vehicle Transmission AB toxins Biofilm
Virulence Susceptibility Exotoxinx Chain
5
© 2014 by McGraw-Hill Education. This is proprietary material solely for authorized instructor use. Not authorized for sale or distribution in any
manner. This document may not be copied, scanned, duplicated, forwarded, distributed, or posted on a website, in whole or part.