Introduction to Biotechnology - College of Science and Mathematics

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Feb 21, 2013 (4 years and 5 months ago)

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Chapter 30

Pathogenicity of Microorganisms

Host
-
Parasite Relationships

Symbiosis

the “living together” of two organisms in a variety of
relationships

commensalism

mutualism

parasitism

Saprophytic organisms

obtain nutrients from dead or decaying organic matter

some are pathogenic but most are considered scavengers


Parasites

Parasites

are organisms that live on or within a host organism
and are metabolically dependent on the host

types of parasites

ectoparasite

lives on surface of host

endoparasite

lives within host




Types of Hosts


Final host

host on (or in) which parasite either gains sexual maturity or
reproduces


Intermediate host

serves as temporary but essential environment for some stage of
parasite’s development

T
ransfer host

is not necessary for development but serves as vehicle for reaching
final host



Reservoir host

nonhuman organism infected with a parasite that can also infect
humans

Parasitism and Disease

Infection

growth and multiplication of parasite on or within host

Infectious disease

disease resulting from infection

Pathogen

any parasitic organism that causes infectious disease

Primary (frank) pathogen



causes disease by direct interaction with
healthy host

Opportunistic pathogen



part of normal flora and causes disease when
it has gained access to other tissue sites or host is
immunocompromised

Pathogenicity

ability of parasite to cause disease

Factors Impacting Outcome of
Host
-
Parasite Relationships

Factors:

number of organisms

present

the degree of
virulence
of pathogen

virulence factors

e.g., capsules, pili, toxins

host’s defenses

or degree of
resistance

Table 30.1

Figure 30.1 Mathematical Expression of Infection

Virulence

Virulence:

degree or intensity of pathogenicity

determined by three characteristics of the pathogen

invasiveness

ability to spread to adjacent tissues

infectivity

ability to establish focal point of infection

pathogenic potential

degree to which pathogen can cause damage to host



Aspects of Pathogenic Potential

Toxigenicity

ability to produce toxins

Immunopathology

ability to trigger exaggerated immune responses

Measuring Virulence

Lethal dose 50 (LD
50
)

number of pathogens that will kill 50% of an experimental
group of hosts in a specified time

Infectious dose 50 (ID
50
)

number of pathogens that will infect 50% of an experimental
group of hosts in a specified time

Figure 30.2:Determination of LD
50

Strain A
LD
50
is 30, B
LD
50

is
50 hence, A is more virulent.

Pathogenesis of Viral Diseases

Fundamental process of Viral infection in a host cell:

maintain reservoir

a place to live and multiply before
infection

enter host

contact and enter susceptible cells

replicate within cells

release from host (immediate or delayed)





Viral infection

spread to adjacent cells

Evade host immune response

be cleared from body of host, establish persistent
infection, or kill host

be shed back into environment




Maintaining a Reservoir

most common
reservoir

of human viruses are humans
and other animals

some viruses are acquired early in host’s life and cause
disease later

most often, viruses are transmitted from one host to
another host and cause infection in a short time frame



Viral Entry

Occurs at a variety of sites:

via body surface

via sexual contact, needle sticks, blood
transfusions, and organ transplants

via insect
vectors

organisms that transmit pathogen from one
host to another


Adsorption

Adsorption

attachment to the cell surface

results from binding of viral protein to host cell
receptors

binding of virus to receptor results in cell penetration
or delivery of viral
nucleic acid

to host cell cytoplasm

Entry of Human Virus Nucleic Acids
into Host Cell

Direct entry of nucleic acid

e.g.,
polio virus
-

enters the host cell and deliver viral nucleic acid into the cytoplasm
of cell


It enters through the human gastrointestinal tract but produces diseases in the
central nervous system. endocytosis and release of nucleic acid from capsid
(uncoating)

e.g.,
pox viruses
-

causes small pox

Fusion of viral envelope


e.g.
influenza


fusion of viral envelope with cell membrane of host


Primary Replication

Primary replication

some replicate
at site of entry
, cause disease at
same site, and do not spread throughout body

others spread to distant sites and then replicate

e.g.,
polio viruses

enter through gastrointestinal tract
but produce disease in central nervous system


Evasion of Host Defenses

begins when the virus first infects the host

for the virus to cause a successful infection, it
must be able to avoid
host immunity

so it can
spread to a sufficient number of host cells to
amplify the number of virions



Viral Spread and Cell Tropism

Viral spread

vary but most common is by
bloodstream

and
lymphatic system

Viremia
-

presence of virus in blood

Spread by way of nerves e.g rabies

Tropisms

Viruses exhibit cell, tissue, and organ specificities


Virus
-
Host Interactions

Cytopathic viruses

local necrosis with ultimate host death

alternatively, can trigger
apoptosis
(programmed cell death)
i.e host cell dies, often before viral replication can occur

Noncytopathic viruses

cause latent or persistent infections


…Non
-
Cytopathic Viruses

Do not immediately cause cell death

cause latent or persistent infections

productive

non
-
cytopathic viruses

produce persistent infection with the release of only a few new
particles at a time

nonproductive

non
-
cytopathic viruses

do not actively make virus at detectable levels for a period of
time (latent infection)

these viruses may become productive by environmental
stressors or other factors




Other Outcomes of Virus
-
Host
Interaction

Clinical illness

some tissues can be quickly repaired after viral damage

e.g., intestinal epithelium

others cannot be easily repaired

e.g., tissues of central nervous system

Integration of viral DNA


may result in transformation of host cells into cancerous cells due
to viral DNA interference with host DNA growth cycle regulation

…Virus Shedding

last step in infectious process is shedding of the
virus in the environment

needed for maintenance of viral source in a host
population

often occurs at same body surface used for
entry of the virus

at this stage host is very
contagious/infectious/stay far…..can spread

in some infections, host is dead (end of host)
and no shedding occurs
-
e.g Rabies


Pathogenesis of Bacterial
Diseases

Maintain a reservoir

Like viral infection Bacteria too need a place to live
before and after causing infection

initial transport to/entry into host

adhere to, colonize, and/or invade host



…Bacterial infection

initially evade host defenses

multiply or complete life cycles
on or in host

damage host

leave host and return to reservoir
or enter new host

Maintaining a Reservoir of the
Bacterial Pathogen

For human pathogens, most common reservoirs
are:

other humans

animals

environment

Transport of the Bacterial
Pathogen to the Host

Direct contact

e.g., coughing, sneezing, body contact

Indirect contact

vehicles (e.g., soil, water, food)

arthropod vectors

fomites


inanimate objects that harbor and
transmit pathogens

Attachment and Colonization by the
Bacterial Pathogen

Adherence structures:

Structures such as such as
pili
and
fimbriae
and specialized
adhesion molecules on bacterium’s cell surface bind to
complementary receptor sites on host cell surface

Colonization:

Colonization is the establishment of a site of microbial
reproduction on or within host

does not necessarily result in tissue invasion or damage



Evasion of Host Defenses by

Bacteria

Successful pathogens can evade destruction by
host :


by:


Formation of
capsule
-

Neisseria gonorrhoeae


production of
leukocidins
-

substance that destroy
phagocytes before phagocytosis can occur

Streptoccocus pneumoniae, Staphyloccocus


use of an
actin tail (cytoskeleton protein)

to spread
into neighboring cells and escape destruction e.g
Shigella


Lysosomal enzymes
-

Mycobacterium tuberculosis
resist
these enzymes probably because of itd waxy
external layer.


Endotoxins

Table 30.4
-
Bacterium polymerised host actin into long tail and
for propulsion from one cell to another and out of the host.

Bacterial Invasiveness

Varies among pathogens

e.g.,
Clostridium tetani

(tetanus) produces a
number of virulence factors (e.g toxin and
proteolytic enzymes ) but is non
-
invasive i.e it
does not spread from one tissue to another.

e.g.,
Bacillus anthracis

(anthrax) and
Yersinia
pestis

(plague) also produce many virulence
factors ( capsule & toxins) and are highly
invasive

e.g.,
Streptococcus

spp. span the spectrum of
virulence factors and invasiveness


Growth and Multiplication of the
Bacterial Pathogen

occurs when pathogen finds
appropriate environment within host

some pathogens actively grow in
blood plasma

bacteremia


presence of viable
bacteria in blood

septicemia


presence of bacteria or
their toxins in blood

Intracellular Pathogens

Bacteria that are able to grow and multiply in various
cells of a host

Facultative intracellular pathogens

can live within host cells or in the environment

e.g.,
Brucella abortus

can grow independently as well as in
macrophages, neutrophils and trophoblast cells

Obligate intracellular pathogens

incapable of growth and multiplication outside of a host

eg., viruses and rickettsia

Leaving the Host

must occur if microbe is to be
perpetuated

most bacteria leave by passive
mechanisms

in feces, urine, droplets, saliva

Regulation of Bacterial Virulence
Factor Expression

Often
environmental factors

control
expression of
virulence genes

e.g.,
Corynebacterium diphtheriae

gene for diphtheria toxin regulated by iron

e.g.,
Bordetella pertussis

expression of virulence genes increased at body
temperature

e.g.,
Vibrio cholerae

gene for cholera toxin regulated by pH,
temperature and other factors


Pathogenicity Islands

Pathogenicity Islands
-

large segments of
DNA that carry virulence genes

acquired during evolution of pathogen by
horizontal gene transfer

e.g., genes for
type III secretion system
(TTSS)

enables gram
-
negative bacteria to secrete and
inject virulence proteins into cytoplasm of
eucaryotic host

Toxigenicity

Intoxications

diseases that result from entry of a specific preformed
toxin into host

Toxin

specific substance that damages host

two main categories in bacteria

exotoxins

endotoxins

Toxemia

condition caused by toxins in the blood of host

Exotoxins

Exotoxins

-

soluble, heat
-
labile, proteins and usually released
into the surroundings as bacterial pathogen grows

humans exposed to exotoxins in three main ways

ingestion

of preformed exotoxin

bacterial colonization

of a mucosal surface

followed by exotoxin
production

colonization of a wound

or abscess followed by local exotoxin production

most exotoxin producers are
gram
-
positive

often travel from site of infection to other tissues or cells
where they exert their effects


Types of Exotoxins

AB exotoxins
-

composed of two
subunits

A subunit



responsible for toxic effect
once inside the host cell

B subunit



binds to target cell od host

specific
host site exotoxins
-
e.g
neurotoxin

membrane
-

disrupting
exotoxinspore
-

e.g forming exotoxins

Superantigens
(enterotoxin of staph)
that stimulate T cells directly to make
cytokines

AB Exotoxins

Composed of two subunits

A subunit



responsible for toxic effect
once inside the host cell

B subunit



binds to target cell

Specific Host Site Exotoxins

can be
AB toxins

neurotoxins

target nerve tissue

e.g., botulinum toxin

enterotoxins

target intestinal mucosa

e.g., cholera toxin

cytotoxins

target general tissues

e.g., nephrotoxin

Membrane
-
Disrupting Exotoxins

do not have separable A and B subunits

two types

pore
-
forming exotoxins

Phospholipases
-
lyses the plasma membrane e.g
-

Clostridium perfringens
-
gas

gagresn

Some Pore
-
Forming Exotoxins

Bacterial Toxins that forms pores in the
membranes:

Leukocidins

membrane
-
disrupting toxins

kill phagocytic leukocytes
-

pneumococci.
Strepto, staphyloccus

Hemolysins
-

other toxin that form pores in
membranes of blood cells

kill erythrocytes, leukocytes, and many other
cells

e.g.,
streptolysin
-
O (SLO)
-

a hemolysin from
Streptococcus pyogenes
-

oxygen
-
sensitive

e.g.,
streptolysin
-
S (SLS)
-

oxygen
-
stable

Hemolytic Reactions

beta
-
hemolysis

complete lysis

observed as zone of clearing around
colony on blood agar

alpha
-
hemolysis

partial lysis

observed as greenish zone around
colony on blood agar

Phospholipase Enzymes

Phospholipase Enzymes

a second
subtype of membrane
-
disrupting
toxins

remove charged head group from
lipid part of phospholipids in host
-
cell plasma membranes

membrane destabilizes, cell lyses and
cell death


Endotoxins

Lipopolysaccharide (LPS)

in gram
-
negative
outer membrane can be toxic to specific
hosts

called
endotoxin
because it is bound to
bacterium and released when organism lyses
and some is also released during
multiplication

toxic component is the lipid portion


Polymicrobial Diseases

Polymicrobial Diseases

-
many
infectious diseases involve the
interactions of more than one
infectious agent

these diseases can be polyviral,
polybacterial, combined viral
-
bacterial,
or polymycotic or protozoan

Dental infections

are examples of
polybacterial disease

Dental Infections

Dental Infections

-
caused by various
odontopathogens

Formation of dental plaque creates
environment for pathogens that
produce acids and other virulence
factors

Figure 30.9: Plaque Development Process

Figure 30.11
-
Microscopic Appearance of Plaque

Periodontal Disease…

Periodontitis

initial inflammatory response to plaque bacteria and tissue
destruction

leads to swelling of tissue and formation of periodontal
pockets

Periodontosis

bone destruction caused by colonization of periodontal
pockets



Periodontal Disease…


Gingivitis

inflammation of gingiva caused by colonization of
periodontal pockets

Treatment, prevention, and control

oral surgery and antibiotic therapy in some cases

plaque removal and good dental hygiene


Bibliography



Lecture PowerPoints Prescott’s Principles
of Microbiology
-
Mc Graw Hill Co.


http://en.wikipedia.org/wiki/Scientific_
method


https://files.kennesaw.edu/faculty/jhend
rix/bio3340/home.html