Download Tortora Ch15 2016-YTKo Lecture

Chapter 15
Microbial Mechanisms of
Pathogenicity
Microbiology, An Introduction 11th edition
Tortora, Funke, Case
Instructor: Yuan-Tih Ko, Ph.D.
Food Science Dept.
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Q&A
• Almost every
pathogen has a
mechanism for
attaching to host
tissues at their portal
of entry.
• What is this
attachment called?
• How does it occur?
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• Pathogenicity
(致病原因學)
• Virulence
The ability to cause disease
by overcoming the defenses of the host
The extent (or degree) of pathogenicity
(致病力, 毒力)
• Virulence Factors Factors that involved in pathogenicity
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病原菌致病 之過程
• General process:
• Gain access
(mucous, skin, parenteral)
• Adhere
(adhesions, ligands, receptors)
• Penetrate
(mechanisms)
• Accumulate waste (toxins)
• Damage
(bacteria, virus, fungi, protozoa,
helminth, algae)
接近  附著  穿入 累積產毒廢物  破壞
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Summarize the Mechanisms of Pathogenicity
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Portals of Entry (進入的門徑) 接近宿主
Gain access
• (1) Mucous membranes (黏膜)
• (2) Skin (皮膚)
• (3) Parenteral (非腸道, 腸以外, 皮下或靜脈注射)
route
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Portals of Entry- (1) mucous membranes -1
• Conjunctiva tract (結膜)
• Delicate membrane cover the eyeball and eyelids
• Conjunctivitis (結膜炎), trachoma (砂眼), neonatal
gonorrheal ophthalmia (新生兒淋病性眼炎)
• Respiratory tract (呼吸道)
• inhaled with droplets of moisture and dust particles
• the most common portal of entry
• Cold (傷風), pneumonia (肺炎), tuberculosis (結核),
influenza (感冒), measles (麻疹), smallpox (天花)
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Portals of Entry- (1) mucous membranes -2
• Gastrointestinal (胃腸道)
• Microbe survive from HCl, stomach enzyme and bile/bile in
intestine can cause disease
• Poliomyelitis(骨髓灰白質炎), hepatitis A, typhoid fever,
amoebic dysentery (阿米巴痢疾), giardiasis (梨形蟲病),
shigellosis (志賀式桿菌性痢疾), cholera (霍亂)
• Transmit to other host via food, water, and contaminated
fingers
• Genitourinary tracts (生殖泌尿道)
• STIs (sexually transmitted infections)
• May penetrate an unbroken mucous membrane
• HIV, genital warts, chlamydia chlamydia(披衣菌), herpes
(泡疹), syphilis (梅毒), gonorrhea (淋病)
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Portals of Entry
• (2) Skin:
• Openings of skins
• Hair follicles (毛囊) , sweat gland dust
• Larvae of hookworm (鈎蟲) bore through skin,
fungi grow on keratin (角質)
• (3) Parenteral route:
• gain access to tissues by inoculation through the
skin and mucous membranes
• Punctures, bites, cuts, injections, surgery, and
other wounds.
•
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The Preferred Portal of Entry
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The Preferred Portal of Entry (偏好的入門)
• Many organisms can cause infections only when they gain
access through their specific portal of entry.
• The bacteria of typhoid fever (傷寒), Salmonella typhi (傷寒桿菌)
• produce all the signs and symptoms when swallowed
(preferred)
• No reaction if the bacteria rubbed on the skin
• The bacteria, Streptococci (鏈球菌)
• produce pneumonia ( 肺炎) when inhaled (preferred)
• No sign if the bacteria swallowed
• Pathogen, Yersinia pestis (鼠疫耶爾森式菌)
• cause plague (鼠疫) from many route
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Virulence (毒力) - ID50
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Numbers of Invading Microbes
• ID50: Infectious dose for 50% of the test population
• The indication of virulence (毒力)of a microbe
• Bacillus anthracis (炭疽菌) through different route
with different ID50
• Skin> Inhalation> Ingestion
Portal of entry
ID50
Skin (cutaneous anthrax 皮膚性炭疽
10-50 endospores
Inhalation
10,000-20,000
endospores
250,000-1,000,000
endospores
病) [kjuˋtenɪəs]
Ingestion
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Bacillus anthracis (炭疽菌) through different route with different ID50
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Potency (效力) - LD50
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• LD50: Lethal dose (of a toxin) for 50% of the test
population
• The potency (效力) of a toxin
• 0.03 ng/kg for botulinum toxin, 250 ng/kg for Shiga
toxin, 1350 ng/kg for staphylococcal enterotoxin in
mice
• Botulinum toxin (肉毒桿菌素) > shiga toxin(志賀桿
菌素 ) > staphylococcal enterotoxin ( 金黃葡球腸毒
素)
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Summarize the Mechanisms of Pathogenicity
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附著 宿主細胞
Adhere (adhesions, ligands, receptors)
-pathogen attachment, a necessary step
接近  附著  穿入 累積產毒廢物  破壞
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Adhesins (粘著素) of pathogen vs. receptor (接受體) of host
• Adhesins on different strains of the same species of
pathogen can vary in structure.
在同種不同亞種病原菌上面的粘著素 結構上會不同
• Different cells of the same host can also have different
receptors that vary in structure.
在相同宿主的不同細胞上面的接受體 結構上會不同
• If adhesins, receptors, or both can be altered to
interfere with adherence, infection can often be
prevented (or at least controlled).
病原菌粘著素、宿主接受體 或兩者可以被更改來干擾附著，常可避免與控制感染
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Adherence
Most adhesins are glycoprotein and lipoprotein
Host receptorSugars/ mannose
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Adherence
(膀胱)
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Adherence
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以細胞壁成份 Glycocalyx 附著
• “Sugar coat” secreted onto the surface
• Firmly layer “capsule”, loosely layer “slime layer”
堅固層 被膜
鬆動層  黏質膜
• Protect it from phagocytosis
• Made of sugar is EPS (extracellular polysaccharide, 胞
外多醣)
• EPS enables a bacterium attach
• Streptococcus mutans, cause dental caries, attaches
itself to the surface of teeth
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以Biofilms 附著
• A microbial community coming together in masses that usually
forms as a slimy layer on a surface
• sometimes can be several layers thick and may contain several
types of microbes.
• represent another method of adherence and are important
because they resist disinfectants and antibiotics.
• This characteristic is significant, especially when biofilms colonize
structures such as teeth (e.g. 牙菌斑), medical catheters, heart
valves, hip replacement components, and contact lenses.
• It is estimated that biofilms are involved in 65% of all human
bacterial infections.
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細胞壁成份 M protein
•Heat-resistant and acid
resistant
•Increase the virulence of
the bacterium,
Streptococcus pyogenes
•Immunity of host depend
on body’s production of an
antibody specific to M
protein
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穿入 宿主細胞
• Penetrate
(mechanisms)
接近  附著  穿入 累積產毒廢物  破壞
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穿入 方式
• Capsules
• Components of cell wall
• Enzymes
• Antigenic variation
• Penetrate host cell cytoskeleton
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Penetrate host with the aid by capsule
• Streptococcus pneumoniae, the causative agent of
pneumococcal pneumonia, increase virulence by the
presence of polysaccharide capsule.
• Encapsuled strains are virulent, but strains without
capsules are avirulent because they are susceptible to
phagocytosis.
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Adherence (Cell wall component) Summary
• Adhesins/ligands of pathogen bind to receptors on
host cells and/or help to penetrate
Adhesin
Pathogen _
• Glycocalyx
Streptococcus mutans (柱牙-鏈球菌)
• Fimbriae
Escherichia coli
• M protein
Streptococcus pyogenes (釀膿鏈球菌)
• Opa protein
Neisseria gonorrhoeae (淋球菌)
• Wax
Mycobacterium tuberculosis (結核桿菌)
• Tapered end
Treponema pallidum (梅毒螺旋體)
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Encapsuled pathogens relate to virulence
• Streptococcus pneumoniae, the causative agent of
pneumococcal pneumonia
• Klebsiella pneumoniae, a causative agent of bacterial
pneumonia
• Haemophilus influenzae, a cause of pneumonia and
meningitis in children
• Bacillus anthracis, the cause of anthrax
• Yersinia pestis, the causative agent of plague.
• capsules are not the only cause of virulence. Many
nonpathogenic bacteria produce capsules, and the virulence
of some pathogens is not related to the presence of a
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capsule.
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藉 酵素 穿入宿主細胞
• Coagulase
Coagulate blood
• Kinases
Digest fibrin clots
• Hyaluronidase
Hydrolyses hyaluronic
acid
• Collagenase
Hydrolyzes collagen
• IgA proteases
Destroy IgA antibodies
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Fibrinogen –CoagulaseFibrin (blood clot)
•Fibrinogen, a
plasma protein
produced by the
liver
•Fibrin clot protect
bacteria from
phagocytosis
•Coagulase(-) are
still virulent
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(導管, e.g. 尿導管)
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藉 酵素 穿入宿主細胞
• Kinases - Digest fibrin clots
• Fibrinolysin (streptokinase), produced by Streptococcus
pyogenes
• Staphylokinase, produced by S. aureus
• Use successfully to dissolve blood clot in heart attack (應
用性 )
• Hyaluronidase-Hydrolyses hyaluronic acid(玻尿酸)
• Streptococci
• hyaluronic acid, a polysaccharide that hold cells together,
in connective tissue
• Involved in the tissue blackening of infected wound, help
the microbe to spread
• Therapeutic use with drug to help drug spread through a
body tissue(應用性 )
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Applications of Microbiology 15.1a
Blocked coronary artery
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Applications of Microbiology 15.1b
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Mechanism of streptokinase (by Streptococcus pyrogenes)
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TORTORA • FUNKE
• CASE
Virulence Factors: Penetrating Host
Tissues
Microbiology
AN INTRODUCTION
EIGHTH EDITION
B.E Pruitt & Jane J. Stein
[insert Virulence_Penetrating.jpg]
PowerPoint® Lecture Slide Presentation prepared by Christine L. Case
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病原菌如何 穿梭 宿主細胞之間?
• Eukaryotic cell contain microfilaments, intermediate
filament and microtubules—cytoskeleton (細胞骨架)
• Actin is used by microbes to penetrate and move thru
and between the host cell
• Once in the cell, Shigella and Listeria species use actin
to propel themselves thru the cell cytoplasm and from
one host to another
• Bacteria use a glycoprotein called cadherin , as a
transport network to bridge the junction from cell to cell
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TORTORA • FUNKE
• CASE
Virulence Factors: Penetrating Host
Tissues
Microbiology
Figure 16.11 A schematic drawing of elements of the
cytoskeleton.
AN INTRODUCTION
EIGHTH EDITION
B.E Pruitt & Jane J. Stein
[insert Virulence_Penetrating.jpg]
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侵入素引起 細胞膜皺摺 幫助 病原菌入侵
• Salmonella strains and E. coli make contact with the host cell
plasma membrane. This leads to dramatic changes in the
membrane at the point of contact.
• The microbes produce surface proteins called invasins ( 侵
入素) that rearrange nearby actin filaments of the
cytoskeleton.
• S. typhimurium invasins cause membrane ruffling (細胞膜皺摺 ):
• the appearance of the host cell plasma membrane to resemble
the splash of a drop of a liquid hitting a solid surface
• is the result of disruption in the cytoskeleton of the host cell
• The microbe sinks into the ruffle and is engulfed by the host
cell.
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Invasin disrupt cytoskeleton of the host cell
侵入素在宿主細胞膜
產生皺摺,進入後重新
組合細胞骨幹的肌動
蛋白
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Figure 15.2 Salmonella entering intestinal epithelial cells as a result of ruffling.
Flagella
Salmonella
typhimurium
Ruffling of
host cell
plasma
membrane
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破壞
• Damage
(bacteria, virus, fungi, protozoa,
helminth, algae)
接近  附著  穿入 累積產毒廢物  破壞
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破壞 機制
• (1) Using the host nutrients 用宿主的營養物
• Siderophore (含鐵攜帶體)
• (2) Direct damage 直接傷害
• Grow, release-rupture, spread
• Reverse phagocytosis process
• Extruding enzymes and motility
• (3) Production of toxins 產生毒素
• Exotoxin
• Endotoxin
• (4) Plasmid, Lysogeny (潛溶性) and pathogenicity
• Code for virulence factors
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•Iron-binding proteins take iron from host
攜鐵體
When iron is needed by a pathogen, siderophores are released into the medium,
where they take the iron away from iron-transport protein (lactoferrin, transferrin,
ferritin), and hemoglobin.
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病原菌 釋出 攜鐵體 強奪 宿主的營養物 - 鐵
• Iron is required for the growth of most pathogenic bacteria.
However, the concentration of free iron in the human body is
fairly low because most of the iron is tightly bound to irontransport proteins, such as lactoferrin(乳鐵蛋白), transferrin (運
鐵蛋白),, and ferritin (儲鐵蛋白),, as well as hemoglobin(血紅素).
• In order to obtain free iron, some pathogens secrete
proteins called siderophores (攜鐵體 Figure 15.3).
• When iron is needed by a pathogen, siderophores are
released into the medium where they take the iron away
from iron-transport proteins by binding the iron even more
tightly.
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病原菌 如何利用 所強奪宿主的鐵?
• (1)Once the iron-siderophore complex is formed, it is taken up by
siderophore receptors on the bacterial surface. Then the iron is brought
into the bacterium.
• In some cases the iron is released from the complex to enter the
bacterium;
• in other cases the iron enters as part of the complex.
• (2) As an alternative to iron acquisition by siderophores, some
pathogens have receptors that bind directly to iron-transport proteins
and hemoglobin. Then these are taken into the bacterium directly along
with the iron.
• (3) Also, it is possible that some bacteria produce toxins when iron
levels are low. The toxins kill host cells, releasing their iron, which is
then available to the bacteria.
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Direct Damage- 直接破壞-1
• Once pathogens attach to host cells, they can cause
direct damage as the pathogens use the host cell for
nutrients and produce waste products.
使用宿主營養源, 產生廢物
• As pathogens metabolize and multiply in cells, the cells
usually rupture. Many viruses and some intracellular
bacteria and protozoa that grow in host cells are
released when the host cell ruptures. Following their
release, pathogens that rupture cells can spread to
other tissues in even greater numbers.
病原菌在宿主細胞內複製, 破裂出細胞, 釋出後散播
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Direct Damage- 直接破壞-2
• Some bacteria, such as E. coli, Shigella, Salmonella, and
Neisseria gonorrhoeae, can induce host epithelial cells to
engulf them by a process that resembles phagocytosis. These
pathogens can disrupt host cells as they pass through and can
then be extruded from the host cells by a reverse
phagocytosis process, enabling them to enter other host cells.
誘導宿主表皮細胞, 類似胞飲作用吞噬入內, 宿主內複製後再以反胞飲作用出
細胞, 侵入另外細胞
• Some bacteria can also penetrate host cells by excreting
enzymes and by their own motility; such penetration can itself
damage the host cell. Most damage by bacteria, however, is
done by toxins.
分泌酵素, 游動穿入宿主細胞, 破壞宿主細胞結構, 以產生毒素最多
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產生毒素 Toxins- 最具破壞力
• Toxin
Substances that contribute to
pathogenicity
• Fatel, fever, cardiovascular disturbance, diarrhea,
shock, inhibit protein synthesis, destroy blood cells,
blood vessels, causing spasms
• Toxigenicity
Ability to produce a toxin
• Toxemia
Presence of toxin the host's blood
• Toxoid
Inactivated toxin used in a vaccine
• Antitoxin
Antibodies against a specific toxin by
toxoid
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Nomenclature of toxins (毒素命名方式)
(1) by characteristics (特性):
Neurotoxin,Cardiotoxin,Heptatotoxin,Enterotoxin,Cytotoxin,
Erythrogenic toxin
(attack nerve, heart, liver, gastrointestinal tract, variety of
cells, blood capillaries)
(2) for the disease they are associated(聯結的疾病):
Diphtheria toxin, Tetanus toxin
(3) for specific bacteria (特定的細菌):
Botulinum toxin, Vibrio enterotoxin
(Clostridium botulinum, Vibrio cholera)
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兩種毒素
Exo vs. endo toxin
*based on their position relative to the microbial cell
* known ~220 toxins, 40% cause disease by damaging cell
membranes)
Food poisoning is intoxication (中毒), not infection
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外毒素 Exotoxin - intoxication (中毒)
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Exotoxin-intoxication (中毒)
Among the most lethal
substance known
1 mg botulinum kill 1
million pigs
Disease-specific
Source
Mostly Gram +
Metabolic product
By-products of growing cell
Chemistry
Fever?
Heat stability
Neutralized by antitoxin
Protein
No
Unstable, destroy at 60-80℃ except
staphylococcal enterotoxin
Yes
LD50
Small
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Three types of exotoxin -- 外毒素3種
(1)A-B toxins
(2) Membrane-disrupting toxin
(3) Superantigens
Most are carried on bacterial plasmid or phages
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Exotoxins- A-B toxins -1
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Exotoxins- A-B toxins-2
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Exotoxins- A-B toxins-3
Receptor-mediated endocytosis
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Exotoxins- A-B toxins-4
Neurotoxic, enterotoxic, cytotoxic etc.
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Exotoxins
•Membrane-disrupting
Membrane-disrupting toxins
破壞細胞膜
• Lyse host’s cells by:
• Making protein channels in the plasma
membrane
• e.g., leukocidins(殺白血球素), hemolysins( 溶血素), S.
aureus
• Disrupting phospholipid bilayer,
• Clostridium perifringens (產氣莢膜梭菌)
• Virulent by killing host cells
• Phagocytes (吞噬細胞),
• Virulent by aiding the escape from
• phagosomes (吞噬泡 )
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Leukocidin vs. Hemolysin
(破壞細胞膜 exotoxins)
• Leukocidin (殺白血球素),
• Act by forming protein channels
• kill phagocyte leukocytes (WBC),
• act on macrophage, tissue phagocytes
• Most produced by staphylococcal, streptococci, and
pneumococci
• Hemolysin ( 溶血素) destroy erythrocytes (RBC)
• Act by forming protein channels
• staphylococcal, streptococci
• Streptolysin (鏈球菌溶血素)
• Lyze WBC, RBS, body cells
• SLO: it is inactivated by oxygen
• SLS: stable in an oxygen environment
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Exotoxins- Superantigens 免疫反應
• Superantigens (超強抗原)
• Cause an intense immune response due to release of
cytokines from host cells
• Superantigen stimulate T-cell nonspecifically proliferation
• T-cells are types of WBC lymphocytes
• T-cell release enormous amount of cytokines
• Cytokines are small protein hormones
• Cytokines enter the blood stream
• Stimulate or inhibit normal cell functions (fever, nausea,
vomiting diarrhea, shock, death etc.)
• Staphylococcal toxin cause food poisoning and toxic
shock syndrome
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麻痺
痙攣
壞疽
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Table 15.2
Exotoxins
Bacteria
Syndrome (toxin)
• Corynebacterium
diphtheriae
Exotoxin
Lysogenic
conversion
A-B toxin. Inhibits
protein synthesis.
+ (tox gene)
diphtheria
• Streptococcus pyogenes Membrane-disrupting. A,
B, C. Erythrogenic.
scarlet fever
• Clostridium botulinum
A-B toxin. Neurotoxin
botulism
• C. tetani
A-B toxin. Neurotoxin
Tetanus, tetanospasmin
• Vibrio cholerae
A-B toxin. Enterotoxin
cholera
• Staphylococcus aureus
Superantigen.
Enterotoxin.
toxic shock syndrome
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+
+
+
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TORTORA • FUNKE
• CASE
Virulence Factors: Exotoxins
Microbiology
AN INTRODUCTION
EIGHTH EDITION
B.E Pruitt & Jane J. Stein
[insert Virulence_Exotoxins.jpg]
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內毒素
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Endotoxins
Source
Gram–
Metabolic product
Present in LPS of outer membrane
Chemistry
Lipid A
Fever?
Heat stability
Yes
Stable (withstand 121℃, 1 hr)
Neutralized by antitoxin
No
LD50
Relatively large
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內毒素 效應
Endotoxic effects
(1) pyrogenic response 發燒
(IL-1)
(2) septic shock 敗血性休克
(TNF)
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(1) The fever (pyrogenic response高熱所產生的) caused by
endotoxins
• When gram-negative bacteria are ingested by phagocytes and
• degraded in vacuoles, the LPSs of the bacterial cell wall are released.
These endotoxins cause macrophages to produce a cytokine called
interleukin-1 (IL-1), formerly called endogenous pyrogen,
• which is carried via the blood to the hypothalamus (下視丘), a
temperature control center in the brain.
• IL-1 induces the hypothalamus to release lipids called prostaglandins
(前列腺素), which reset the thermostat in the hypothalamus at a
higher temperature.
• The result is a fever.
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Endotoxins
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Endotoxins
下視丘
前列腺素
hyp
腦垂體
恆溫
下視丘
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TORTORA • FUNKE
• CASE
Virulence Factors: Endotoxins
Microbiology
AN INTRODUCTION
EIGHTH EDITION
B.E Pruitt & Jane J. Stein
[insert Virulence_Endotoxins.jpg]
PowerPoint® Lecture Slide Presentation prepared by Christine L. Case
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(2) Shock (休克 ) – G (-) cause endotoxin septic shock
•
Shock refers to any life-threatening decrease in blood pressure. Shock
caused by bacteria is called septic shock (細菌性之敗血性休克).
• Gram-negative bacteria cause endotoxic shock.
• Like fever, the shock produced by endotoxins is related to the secretion
of a cytokine by macrophages.
• Phagocytosis of gram-negative bacteria causes the phagocytes to
secrete a polypeptide called tumor necrosis factor (TNF), or cachectin.
•
TNF binds to many tissues in the body and alters their metabolism in a
number of ways.
• One effect of TNF is damage to blood capillaries; their permeability is
increased, and they lose large amounts of fluid.
• The result is a drop in blood pressure (低血壓) that results in shock.
• Low blood pressure has serious effects on the kidneys, lungs, and
gastrointestinal tract.
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Septic shock (細菌性之敗血性休克)
• Another mechanism that causes septic shock is discussed in the box in
Chapter 16.
• In addition, the presence of gram-negative bacteria such as
Haemophilus influenzae type b
• in cerebrospinal fluid causes the release of IL-1 and TNF.
• These, in turn, cause a weakening of the blood–brain barrier that
normally protects the central nervous system from infection. The
weakened barrier lets phagocytes in, but this also lets more bacteria
enter from the bloodstream.
• In the United States, 750,000 cases of septic shock occur each year.
One-third of the patients die within a month, and nearly half die within 6
months.
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血腦障壁的功能
• 血腦障壁 (blood–brain barrier)有幾項重要的
功能：
• 保護腦部不受血液中「外來物質」的中傷
• 保護腦部遠離來自身體其他部位之荷爾蒙與
神經傳導物質之影響
• 維持腦中環境的衡定
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血腦障壁的崩解
• 高血壓(hypertension or high blood pressure)：高血壓會
使 血腦障壁門戶洞開
• 發育：出生時 血腦障壁並沒有發育完全
• 高張狀態：血液中高濃度的物質可能會撬開 血腦障壁的大門
• 微波：暴露在微波之中可能會打開血腦障壁
• 放射線：暴露在放射線之中可能會打開血腦障壁
• 感染：接觸感染源會使 血腦障壁出現漏洞
• 創傷 ，局部缺血，發炎，壓迫：腦部的損傷可能會打開血腦
障壁
來自 Loyola University School of Medicine 以及Society for Neuroscience
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Characters of endotoxin
• All endotoxins produce the same signs of syndrome
• Chill, fever, weakness, generalized aches, shock
• Cause “disseminated intravascular clotting (DIC)”:
散播性內管壁凝血
• activate blood-clotting proteins, 血塊破壞微血管
• Do not promote the formation of effective antitoxins against
CHO component of endotoxin
• S. typhi (the causitive agent of typhoid fever)
• Proteus spp. (urinary tract infection)
• Neisseria meningititus (meningococcal meningitis)
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測內毒素存在的方法
• Materials that have been sterilized may contain endotoxin
• LAL assay (Limulus amoebocyte 鱟lysate, horseshoe crab)
• -detect minute amt of endotoxin
• Endotoxin cause the ameobocyte in the hemolymph to
release clotting protein to precipitate
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Plasmid, Lysogeny and pathogenicity
質體, 潛溶性, 影響致病的毒力
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質體影響致病的毒力
• (1) Plasmid code for virulent factor
• Encoded by plasmid genes
• Tetanospasmin (破傷風痙攣素), heat-labile熱不穩定
enterotoxin, staphylococcal enterotoxin
• Dextransucrase by Streptococcus mutans
• Adhesins, coagulase by Staphylococcus
aureus
• Carry genes for antibiotic resistance, toxins,
capsules and fimbriae
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• (2) Lysogenic
conversion
潛溶性
影響致病的毒力
• A change in the characteristic of bacteria due to
prophage
• Bacteriophage incorporate DNA into bacterial chromosome
• A latent state
• The bacteria is immune to infection by the same type of
phage
• Diphtheria, erythrogenic, staphylococcal enterotoxin,
pyrogenic, botulinum, cholera
• Shiga toxins in E. coli O157
• Can result in bacteria with virulence factors, such as
toxins and capsules
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病毒致病性
• 1. Viruses avoid the host’s immune response by growing
inside cells.
• 2. Viruses gain access to host cells because they have
attachment sites for receptors on the host cell.
• 3. Signs of viral infections are called cytopathic effects
(CPE).
• 4. Some viruses cause cytocidal effects (cell death), and
others cause noncytocidal effects.
• Infected cells produce interferon (干擾素)
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病毒如何躲避宿主防禦系統?
• Their attachment mimic ( 假裝) the neurotransmitter
acetylcholine  the virus enter the host cell along with
the neurotransmitter
• HIV hide (躲避) its attachment site sites from the immune
response, and attack (攻擊) the components of the
immune system directly
• Attack cells which have the CD4 protein, surface
marker , of most immune cells
• Virus surface folded (摺疊) to form ridges and valleys
• CD4 are long and slender for HIV to reach the
binding sites, whereas Ab molecules made against
HIV are too large to destroy -- > 很難破壞HIV
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CPE (Cytopathic effects 細胞病變效應,用於診斷病毒感染)
• stopping of mitosis
• lysis
• the formation of inclusion bodies
• cell fusion
• antigenic changes
• chromosomal changes
• Transformation
• Most cells cease growing in vitro when they come
close to another cells, called “contact inhibition”.
• Lose contact inhibition
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病毒引起 細胞病變效應-1
融合細胞
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病毒引起 細胞病變效應 -2
肉瘤病毒引起細胞失去
contact inhibition
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Figure 15.8 Human fibroblasts are transformed by Rous sarcoma virus.
Rounded up
fibroblast
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病毒之CPE
(細胞病變效應)
小兒痲痺
腺
桿狀
Form syncytium 融合細胞
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Pathogenic Properties of Fungi, Protozoa, Helminths, and
Algae
Pathogens
Cause of symptoms of
fungal infections
capsules, toxins, and allergic
responses.
damage to host tissue or by
the metabolic waste products
of the parasite.
change their surface antigens
while growing in a host so the
host’s antibodies don’t kill the
protozoa.
produce neurotoxins that
cause paralysis when
ingested by humans.
protozoal and helminthic
diseases
Some protozoa
Some algae
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黴菌致病性 -1
• Fungal waste products may cause symptoms
• Chronic infections provoke an allergic response
• Tichothecene toxins inhibit protein synthesis
• Fusarium-grain, rice, wheat
• Proteases
• Candida, Trichophyton-modify host cell membrane
• Capsule prevents phagocytosis
• Cryptococcus
• Ergot toxin-sclertia ( 麥角毒素 )
• Claviceps-alkaloid Claviceps-alkaloid cause
hllumination
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黴菌致病性 -2
• Aflatoxin (AFX) 黃麴毒素
• Aspergillus flavus
• Carcinogenic to liver
• Mycotoxins 黴菌毒素
• Neurotoxins: Phalloidin, amanitin
• Amanita phalloids Amanita phalloids
• The death angel (死亡天使)
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Pathogenic Properties of Protozoa (原蟲致病性)
• Presence of protozoa
• Plasmodium-cause malaria 瘧疾
http://www.youtube.com/watch?v=AvscsJadW0k&feature=related
• Taxoplasma-attach phagocyte, prevent normal
acidifaction and digestion
• Carry by fly, host produce Ab, but microbe make
up 1000 Ag
• Giardia lamblia-cause giardiasis 梨形蟲病
http://www.youtube.com/watch?v=L8UTpc37Wx8&playnext=1&list=PLE4634B15
51CA015F
• Trypanosoma-cause sleeping sickness 嗜睡病
由 tsetse fly (舌蠅, 為酣睡症傳媒) p627
http://www.youtube.com/watch?v=BgQVzbL0zJs&feature=related
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嗜睡病原蟲的Antigenic variation逃避防禦系統
• Protozoan waste products may cause symptoms
• Avoid host defenses by
• Growing in phagocytes
• Antigenic variation
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Pathogenic Properties of Helminths (蠕蟲致病性)
• Parasite use host tissue for growth
• Round worm, Wuchereria bancrofti cause
elephantiasis (象皮病,血絲蟲病)
• Block lymphatic circulation, cause leg and body
swelling
• Presence of parasite interferes with host function
• Parasite's metabolic waste can cause symptoms
血絲蟲幼蟲在人體的淋巴系統內繁殖使淋
巴發炎腫大，使人體外觀類似於象的皮膚
和腿，一般傳染的途徑是蚊蟲叮咬
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引起象皮病的一種蠕蟲
http://www.youtube.com/watch?v=nZPh
QOr9LgQ&feature=fvwrel
Brugia malayi.
http://www.youtube.com/watch?v=qRmNP
b4ODZw&feature=related
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Pathogenic Properties of Algae (藻類致病性)
• Neurotoxins produced by dinoflagellates 渦鞭毛藻
• Alexandrrium
• Saxitoxin (STX) 河蚌毒
• Paralytic shellfish poisoning (PSP) 河豚毒
• Consume mollusk during red tides
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Portals of Exit
• Just as pathogens have preferred portals of entry, they
also have definite portals of exit.
• Respiratory tract
• Coughing, sneezing
• Gastrointestinal tract-the most common
• Feces, saliva
• Genitourinary tract
• Urine, penis, vaginal secretions
• Skin discharge, tissue
• Blood
• Biting arthropods, needles/syringes
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