1
Q
What is a pathogen?
A
A microorganism that is able to cause disease in another organism
2
Q
What is pathogenicity?
A
the ability to induce disease in a host organism
3
Q
What is virulence?
A
how pathogenic a microbe is
4
Q
What are the determinants of virulence?
A
The genetic or biochemical or structural features that enable a pathogen to produce disease in a host.
5
Q
Virulence and pathogenicity both modify the activities and functions of the other with the outcome dependent on…
A
the virulence of the pathogen and the host defence mechanisms
6
Q
What are the underlying mechanisms of bacterial pathogenicity?
A
Invasiveness and the ability to produce toxins (toxigenesis)
7
Q
The ability to invade tissues: invasiveness….
A
- Mechanisms for colonization: adherence and inital multiplication
- Ability to bypass or overcome host defence mechanisms
- Production of extracellular substances which facilitate invasion: adhesins like fimbriae
8
Q
The ability to produce toxins: Toxigenesis…
A
- Bacteria produce exotoxins and endotoxins.
9
Q
What are exotoxins?
A
Toxins that are released from bacterial cells and may act at different sites to the site of infection e.g. Botulinum or Cholera toxin.
10
Q
What are endotoxins?
A
Toxins that are structural components of the cell walls of Gram-negative bacteria e.g. capsule or LPS
11
Q
Is it true that a pathogen needs to enter the host in order to establish infection?
A
Yes
12
Q
Which ways can the pathogen enter the host to establish infection?
A
- Through common pathways, such as: respiratory, gastro-intestinal, urinary tract, genital tract
- Through other pathways of infection: insect bites, accidental or surgical trauma to the skin
- Way of opportunistic pathogens: these are often carried as part of the normal human microflora, and are a ready source of infection in the compromised host.
- Primary pathogens (a microorganism that causes disease in a healthy host with a normal immune system)
13
Q
Opportunistic pathogens usually don’t cause damage, but they can if the environment changes.
A
Opportunistic pathogens usually don’t cause damage, but they can if the environment changes.
14
Q
Is it true that entry of primary pathogens into the host is usually more complex?
A
Yes
15
Q
Give 2 examples of primary pathogens
A
- Bordetella pertussis (respiratory pathogen)
- Neisseria gonorrhoeae
16
Q
Why is the transmission of Bordetella pertussis into hosts usually complex?
A
Because it survives poorly outside the host, so transmission requires close contact with infectious respiratory droplets.
17
Q
Why is the transmission of Neisseria gonorrhoeae into hosts usually complex?
A
because direct person-to-person mucosal contact is required (humans are only natural host, very poor survival in environment)
18
Q
What is N. gonorrhoaea’s only natural host?
A
Humans
19
Q
Why is gonorrhoea an obligate pathogen?
A
- Because it only infects humans and cannot survive independently outside a human host.
- It must infect a human to facilitate its transmission from one person to another and survive.
20
Q
Give some examples of gastrointestinal pathogens
A
Salmonella, Shigella and Campylobacter
21
Q
What is the primary source of gastro-intestinal pathogens?
A
Primary source is environmental (contaminated water or food)
22
Q
Is it true that gastrointestinal pathogens need to be viable in many different environments?
A
Yes. The environments that they’re viable in determine their reservoirs and potential modes of transmission
23
Q
Are gastrointestinal pathogens restricted to a single physiological state?
A
No
24
Q
Is it true that gastrointestinal pathogens respond to environmental stimuli?
A
Yes
25
Is it true that gastrointestinal pathogens confer improved capacity for survival in adverse conditions?
Yes
26
Which environmental factors affect pathogens?
Temperature, pH tolerance, and anaerobiosis
27
How can temperature affect pathogens?
It can affect their growth and pathogenicity
28
How can pH affect pathogens?
It can affect their growth and pathogenicity
29
Which pathogens are commonly affected by temperature?
Listeria and Legionella
30
Which pathogens are commonly affected by pH?
Helicobacter pylori, Salmonella, Gram positive bacteria
31
Which pathogen is affected by Anaerobiosis?
Clostridium
32
What is anaerobiosis?
Lack of oxygen
33
Is it true that microbes define themselves by the temperature that they grow in?
Yes
34
What temperatures do Psychrophile's grow best in?
Grow best at relatively low Temp
0 - 20 degrees
Optimum:10-15°C
35
What temperatures do Psychrotroph's grow best in?
Able to grow at low Temp but prefer moderate Temp
0 - 25 degrees+
Optimum: 15-30°C
36
What temperatures do Mesophile;s grow best in?
- Most known bacteria esp. those living in association with warm-blooded animals
- 10 - 45 degrees range
- Optimum: 30-40°C
37
What temperature do thermophiles grow best in?
- Among all thermophiles is wide variation in optimum and maximum T.
- Highest optima in the Archaea
- 45 - 100 degrees range
- 45-70°C optimum
38
Why are mesophiles a concern for us?
Because they grow at our body temp
39
Is it true that most bacteria and archaea are poorly adapted to growing at temperatures above their optimum?
Yes
40
What happnes to the growth of bacteria beyond maximum?
There is a rapid decrease in growth, as high temperatures have adverse effects on important cellular processes.
41
What is cold shock?
A decrease in temperature
42
What happens when bacteria, like e coli, undergo cold shock?
There is a transient inhibition of most protein synthesis – causes a growth lag (acclimation phase)
43
What happens when e coli experiences cold shock?
- Protein synthesis for most of its core genes stops and CSPs are rapidly produced instead, and bacterial growth resumes
- CSPs protect the e coli dna and allow an organism to grow
44
Is it true that some CSPs are essential to resume growth at low temperature?
Yes
45
What diesease does the bacteria listeria cause?
Listeriosis
46
How commmon are listeria infections?
They are quite rare
47
Is listeria a food pathogen?
Yes
48
Q: Who is most susceptible to Listeria monocytogenes infection?
Pregnant women (especially late pregnancy) → risk of miscarriage, stillbirth
Immunocompromised individuals
49
Is it true that listeria is widespread in the environment and if so, where?
Yes, listeria is widespread in the environment and is found in: vegetation, water, soil, wild or domestic animals and people
50
What temperature range is listeria capable of growing over?
A wide temperature range of 4 - 40 degrees celcius
51
How does listeria spread?
From contaminated food
52
Because listeria can grow and multiply over low temperatures, where is it commonly found?
- Meats
- Unpasteurized milk
- Contaminated vegetables (salads, coleslaw)
- Seafood
- Food that require no further heating or processing
- Long shelf life
53
Is it true that listeria can survive and multiply in fridge temperatures?
Yes
54
Listeria has particular proteins that allows it to invade mammalian cells. What are these proteins called?
Internalin A and B
55
What are Listeria's virulence factors?
- Invasion of mammalian cells
- escape from a single membrane vacuole
- Movement through the cytoplasm, cell-to cell spread (Required for escape from double membrane vacuole).
56
How does listeria escape the vacuole produced by the body?
By forming a pore in the vacuole using the LLO cytotoxin
57
How does listeria move through the cytoplasm?
By using the actin to propel itself through the cytoplasm
58
What temperatures can listeria grow at?
1 - 44°C, including in refrigerators!
59
Is it true that listeria can survive freezing and relatively high cooking temperatures?
Yes
60
What temperature should kill Listeria?
>70°C throughout a food for at least two minutes will kill/disable Listeria
61
What other types of food can Listeria grow in?
- grow in foods with 12% NaCl
- grow in food with a pH range of 4.4- 9.8
- food preservatives have little effect on Listeria
62
What can be used to prevent and treat Listeria?
- Disinfectants control Listeria on surfaces and equipment
- Avoid unpasteurised milk products
- Avoid coleslaw & deli meats
- Cook meat thoroughly, & re-heat after refrigeration (or avoid meat!)
- Antibiotics not really useful unless disease diagnosed very early
63
Is pH also a determiner of pathogenicity?
Yes
64
Describe Legionella pneumophila
- Named after The American Legion - “Legionnaires” disease
- Isolated after outbreak at AL Convention 1976
- Fever and extensive lung damage
- Killed 29 people (149 were ill!)
- Motile, aerobic Gram-negative rod
- Complex nutritional requirements
- Form biofilms (particularly in air-conditioning cooling towers)
- Live inside protozoa e.g. Acanthamoeba
- In Humans enter phagocytic cells esp. macrophages
- Humans are probably an opportunistic host!
65
How does temperature affect L. pneumophila?
- Temp affects motility, piliation, and virulence of L. pneumophila
- Cells make more flagella and type IV pili at 30°C than at 37°C
- L. pneumophila less virulent at 24°C than at 37°C
- Humans are an accidental host
- Legionella Hsp60 is implicated in attachment and entry into human epithelial cells.
66
How many pH units do most bacteria/archaea grow?
Most bacterial/archaeal species grow over a range of 3 pH units- A 1000-fold range in conc. of [H+]
67
With pH, growth is quite symmetrical, pH effect is gradual
With pH, growth is quite symmetrical, pH effect is gradual
68
- pH follows a logarithmic scale
- pH 7-> 8 represents an increased number of hydrogen ions by 10 fold
- pH follows a logarithmic scale
- pH 7-> 8 represents an increased number of hydrogen ions by 10 fold
69
Acidophiles...
“loves acid” – less that pH 5 (ish)
70
Neutrophiles...
“loves neutral” – around pH 7
71
Alkaliphiles...
“love alkaline” – above pH 9 (ish)
72
Why do obligate acidophiles require a low pH?
For growth (e.g. Thiobacillus species)
73
Why do obligate acidophiles require a high [H+]?
For membrane stability
74
Which microorganisms are usually obligate acidophiles?
Many Archaea, (i.e. Sulfolobus and Thermoplasma)
75
76
What do obligate alkaliphiles use to make ATP?
They use a proton motive force, even though their membrane surface is so alkaline
77
Is it true that many fungi are acidophiles?
Yes
78
What pH can the eukaryotic alga Cyanidium grow at?
pH 0
79
What pH can obligate alkaliphiles grow up to?
can grow up to pH 10 (soda lakes & high carbonate soils)
80
Why do obligate alkiliphiles require a low [H+]?
For membrane stability
81
What do Alkaliphilic Bacillus species use for transport and motility?
A sodium gradient provides the energy for transport and motility.
82
What is the optimal growth pH?
The environmental pH
83
Why does most organisms intracellular pH stay around 7?
To prevent damage to acid/alkali labile macromolecules
84
What are the major problems caused by acidic conditions?
- It's difficult to generate energy in acidic conditions
- It's difficult to acquire nutrients
- It becomes difficult to protect DNA and proteins, which are critical for survival
- Chaperone proteins and alkalisation of the periplasm help cells to survive well in these conditions
-
85
What are the characteristics of H. pylori?
- Gram-negative curved rod
- Highly motile with 4-7 polar flagella
- C-source - glucose, amino acids, organic acids
- Internal pH 7.0-7.3
- Small, 1.7 Mbp genome
86
What diseases can Helicobacter pylori cause?
- Gastric and duodenal ulcers
- Development of gastric cancer
87
What are the main virulence factors of Helicobacter pylori?
- Flagella
- Urease –neutralises acidic pH of stomach
- Adhesins
- Vacuolating toxin
88
Q: What does H. pylori use urease for?
A: To increase the local pH by producing ammonia, allowing it to survive in the acidic stomach environment.
89
What can be used to prevent and treat h. pylori infection?
Antibiotics, which can be used to cure disease and prevent ulcer recurrence.
90
How do we know H. pylori causes ulcers?
- H. pylori was found in ulcer lesions and successfully grown in pure culture, but scientists couldn’t test it in animals.
- To prove it caused ulcers, Barry Marshall drank a culture of H. pylori himself. Two weeks later, he developed stomach inflammation and H. pylori was detected in his stomach.
- After recovering naturally, his experiment provided strong evidence that H. pylori causes ulcers—work that later earned him a Nobel Prize.
91
How does H. pylori survive in stomach acid?
- Colonises the mucin layer of the gastric mucosa - NOT the lumen of the stomach
- Whilst swimming H. pylori produces the enzyme urease.
- Urease hydrolyses urea (from gastric cells) to make ammonia and CO2.
- Ammonia neutralises stomach acid around the H. pylori
92
What are the characteristics of Salmonella typhimurium?
Motile gram-negative rod
93
What disease does Salmonella typhimurium cause?
Gastroenteritis, diarrhoea
94
What are the reservoir's of salmonella?
Humans, livestock animals, reptiles
95
What are the modes of transmission of salmonella?
- Contaminated food –poultry meat or eggs
- Also milk, ice cream & marijuana!
96
What are the main virulence factors of salmonella?
- Acid tolerance response
- Adhesins
- Invasion of intestinal mucosal cells
- Type III secretion system
97
How can salmonella be prevented and treated?
- Proper food handling
- Antibiotics
98
What does S. typhimurium have to survive to cause disease?
To cause disease S. typhimurium has to survive passage through the stomach
99
Obligate aerobes...
- Require O2 for growth
- O2 is the final electron acceptor in aerobic respiration.
100
Obligate anaerobes...
- Do not need or use O2
- O2 is a toxic substance, which either kills or inhibits growth.
- Obligate anaerobes live by fermentation, anaerobic respiration, bacterial photosynthesis or methanogenesis.
101
Facultative anaerobes/aerobes...
- both aerobic and anaerobic
- In anaerobic conditions (no O2) grow by fermentation or anaerobic respiration
- In the presence of O2 switch to aerobic respiration.
102
What are aerotolerant anaerobes
- fermentative bacteria, insensitive to O2
- Ferment whether or not O2 is present
103
Microaerophile
Microaerophile
104
What are the responses to oxygen in the environment?
- Various oxygen radicals are generated by cells in presence of O2
- The superoxide free radical is highly toxic
- Chlorophyll and other pigments generate singlet oxygen in the presence of light, very potent oxidising agent
105
Q: How do organisms deal with toxic oxygen (ROS)?
- Most organisms use superoxide dismutase (SOD) to detoxify superoxide.
- Most use catalase to break down hydrogen peroxide (H₂O₂).
- Some (e.g. lactic acid bacteria) use peroxidase instead of catalase.
- Carotenoids protect against singlet oxygen (in photosynthetic organisms).
- Obligate anaerobes lack these enzymes → oxygen is toxic to them
106
What do Reactive Oxygen Species (ROS) include?
- Superoxide (O₂⁻)
- Hydrogen peroxide (H₂O₂)
- Singlet oxygen
- These damage DNA, proteins, and membranes. So cells need defences to protect them from this.
107
How do carotenoid pigments protect photsynthetic organisms from singlet oxygen?
- React with the singlet oxygen radical
- lower it a non-toxic "ground" (triplet) state
- Carotenoids "quench" singlet oxygen radicals
108
.
109
What makes Clostridium spp. obligate anaerobes?
- Lack SOD, catalase, peroxidase
- No cytochromes (no respiratory chain)
- Cannot detoxify ROS → oxygen is lethal
110
111
Where is Clostridium botulinum
commonly found?
In soil and sediments
112
What does clostridium botulinum cause?
botulinum food poisoning
113
How potent is the Botulinum toxin?
Botulinum toxin extremely potent (ingesting 70𝜇g can kill)
114
Is it true that clostridia form spores that can survive some food processing?
Yes
115
Tinned foods are processed to protect consumers from ........... contamination
Botulinum
116
What kind of environment can poorly canned foods create?
Poorly canned foods can create an anaerobic environment
117
Poorly canned foods can create an anaerobic environment. What is the issue with this?
This allows spores to germinate and produce toxins
118
Is it true that different strains of clostridium botulinum produce one of 7 exotoxin types (A,B,C1,D,E,F,G)?
Yes
119
How does the botulism toxin affect the body?
- Toxins block the release of neurotransmitter acetylcholine, resulting in: double vision, slurred speech, decreased saliva, difficult swallowing general weakness.
- Paralysis, respiratory failure, death
120
Clostridium botulinum exotoxin types C and D are encoded by what?
- Types C and D are encoded by lysogenic bacteriophage that infect the bacteria
121
What can destroy the boutlism toxin?
Cooking, as it is heat labile
122
What type of bacteria is C. difficile?
Gram positive
Obligately anaerobic
Spore former
123
What facilitates the growth of C. difficile?
- Antibiotics
- This is because they affect normal microbiota and C. difficile overgrows
124
What toxins does C. difficile produce?
Toxins A and B, which are large endotoxins
125
What happens to the body as a result of C. difficile toxin production?
- Toxins cause diarrhoea and lesions on the colon surface, resulting in extensive tissue damage (pseudomembranous colitis)
126
Describe Clostridium tetani
- Causative agent of tetanus (lockjaw)
- Infection from trauma or a puncture wound leading to tissue contamination
- Caused by release of a exotoxin by C. tetani
- Exotoxin circulates binds to neuronal receptors
- Toxin fixes to gangliosides blocking release of neurotransmitters glycine and γ-amino butyric acid (GABA).
- Prevents contraction of antagonistic muscles; therefore, muscle spasms and convulsions (lockjaw) may occur
- Was very common cause of death until vaccine to toxin developed
127
What do the hosts of clostridium tetani usually die from?
- Respiratory paralysis
128
What disease does the bacteria Legionella pneumophila cause?
Legionnaire's disease
129
Salmonella typhimurium acid tolerance response
Salmonella typhimurium must survive stomach acid to cause infection.
Cells grown at neutral pH survive only down to pH 4.
Cells adapted to mild acid (pH 6) can survive as low as pH 3.
The Fur protein (iron regulator) also controls acid shock proteins, sensing both iron and pH through separate mechanisms — proven by mutants that respond to one but not the other.
130
Is legionnaire's disease a type of pneumonia?
Yes
131
What type of environments is Legionella pneumophila naturally found in?
aquatic environments (like water systems)
132
Why are humans accidental hosts of Legionella pneumophila ?
Because Legionella pneumophila normally infects protozoa (microscopic aquatic organisms)
133
Why are humans accidental hosts of Legionella pneumophila ?
Because Legionella pneumophila normally infects protozoa (microscopic aquatic organisms)
134
How do humans get infected with Legionella pneumophila?
By inhaling contaminated water droplets
135
What does motility mean?
The ability to move (using flagella)
136
What does piliation mean?
presence of pili (hair-like structures that help attach to surfaces or host cells).
137
How does temperature affect Legionella pneumophila?
- ~25–30°C (water): ↑ motility & attachment → survives in environment
- 37°C (human body): ↑ virulence → infects host cells
- Adapted to aquatic environments but becomes pathogenic at body temperature
138
Do motility, piliation and virulence depend on temperature?
Yes
139
What happens to Legionella pneumophila at human body temperature?
- Heat shock is induced, which is stress from high temperature environments
- This stress response makes it more invasive — it switches to a mode that allows it to invade and survive inside human cells.
140
Describe the Legionella Hsp60 (Heat shock protein 60)
- A protein produced in response to heat stress.
- It helps the bacterium attach and enter human epithelial cells (cells lining the lungs).
- Hsp60 belongs to a large group of proteins called “immunodominant common bacterial antigens” — these are proteins recognized strongly by the immune system and shared across many bacteria.
141
Legionella pneumophila temperature summary
- Cool temps (<37°C) → more flagella/pili → better survival in environment.
- Warm temps (37°C) → activates heat shock proteins → increases virulence in humans.
- Humans are not the natural host — Legionella is adapted to water and protozoa but can “accidentally” infect humans through aerosolized water.
142
How does the botulinum toxin inhibit muscle contraction?
- Because it prevents the release of acetylcholine from vesicles, resulting in a lack of stimulus to the muscle fibres, and therefore a lack of contraction.
143
144
What do the hosts of Clostridium tetani usually die from?
respiratory paralysis
145
146
Describe the action of Urel- the H. pylori pH sensor
- Urel is an inner membrane protein.
- Transports urea into cytoplasm ONLY when cell is in low pH environment.
- pH detected by via sensory residues on the periplasmic face of UreI
147
What is the acid tolerance response (ATR) in Salmonella typhimurium?
- Adaptation to mild acid (≈ pH 6)
- Induces acid shock/protective proteins
- Allows survival at much lower pH
148
What pH can Salmonella typhimurium survive?
- Normal cells → survive to ~pH 4
- Acid-adapted cells → survive to ~pH 3
149
What is the role of the Fur protein in Salmonella acid response?
- Fur = regulator
- Controls acid shock proteins
- Senses: iron and ph via separate pathways
150
Mild acid trains Salmonella to survive stronger acid
Mild acid trains Salmonella to survive stronger acid
151
How do organisms detoxify reactive oxygen species (ROS)?
Superoxide dismutase (SOD) → superoxide → H₂O₂
Catalase → H₂O₂ → H₂O + O₂
152
What enzyme can replace catalase in some bacteria?
Peroxidase
Used by e.g. lactic acid bacteria
153
How do some organisms protect against singlet oxygen?
Carotenoids
Neutralise singlet oxygen
Seen in photosynthetic organisms
154
Why is oxygen toxic to obligate anaerobes?
Lack SOD and catalase/peroxidase
→ Cannot detoxify ROS
→ Oxygen becomes lethal
155
“SOD first, catalase cleans up”
“SOD first, catalase cleans up”
156
What are common routes of pathogen entry into the host?
- Respiratory tract
- Gastrointestinal tract
- Urinary/genital tract
157
What are other routes of pathogen entry into the host?
- Insect bites
- Trauma or surgery
158
Primary pathogens cause disease in healthy individuals and often require specific transmission routes
Primary pathogens cause disease in healthy individuals and often require specific transmission routes
159
What pathogen causes listeriosis?
Listeria monocytogenes
160
What are the virulence factors that Listeria monocytogenes uses to avoid extracellular immune detection?
- Internalin A/B → cell invasion
- Listeriolysin O (LLO) → escape phagosome
- ActA → actin-based motility
- Forms actin tails → cell-to-cell spread
161
Is Legionnaires’ disease a case of severe pneumonia?
Yes
162
Is it true that H. pylori lives in the mucus layer, not the stomach lumen ?
Yes
163
Does clostridium botulinum cause spores?
Yes
164
Microbial Pathogens
flashcards
Decks in class (10)
# Cards
-
Introduction and Environment164
-
Fungal Pathogens127
-
Lecture 3: Mycobacterial infection: Leprosy69
-
Lecture 4: Mycobacterial infection: Tuberculosis60
-
Lecture 5: Flagellated Protozoa: American Trypanosomes- Chagas Disease I90
-
Lecture 6 + 7: Flagellated Protozoa: American trypanosomes II + Flagellated protozoa: African trypanosomes (Tuesday 28th October)97
-
Lecture 8: African Trypanosome IIs49
-
Lecture 9: African trypanosomes45
-
Lecture 10: Malaria; Transmission and Epidemiology91
-
Lecture 11: Malaria Entomology and Vector Control65
