Bacteriology Flashcards
1
Q
Why are two-component systems important for bacteria?
A
They are essential for monitoring changes in the environment and responding to them
2
Q
Which two components constitute a two-component system?
A
- Sensor kinase
- Response regulator
3
Q
Where are sensor kinases in two-component systems often located?
A
Cytoplasmic membrane
4
Q
What is the function of the sensor kinase in two-component systems?
A
Detection of environmental signal, after which it autophosphorylates
5
Q
Where are response regulators in two-component systems often located?
A
Cytoplasm
6
Q
What is the function of response regulators in two-component systems?
A
DNA binding protein -> regulates gene transcription
7
Q
True or false: a response regulator always has the same effect on the genes it regulates
A
False; response regulators can be inhibitory for one gene, whilst activating another
8
Q
What are bacterial processes (partially) regulated by two-component systems? (5)
A
- Bacterial mobility
- Spore formation
- Regulation of metabolism
- Quorum sensing
- Stringent response
9
Q
True or false: all bacteria are able of movement
A
False; some bacteria are immmobile
10
Q
How will a bacterium move
1. When no attractant is present
2. When attractant is present
3. When repellent is present
A
- No attractant = random movement
- Attractant = targeted movement
- Repellent = targeted movement away
11
Q
What drives (targeted) bacterial movement?
A
Presence of attractans/repellents
12
Q
By which process can bacteria mostly find directionality?
A
Chemotaxis
13
Q
In which way do chemotactic two-component system differ from others?
A
Don’t influence gene transcription, but rather modify existing proteins
14
Q
What is the main protein that is modified when a chemotactic two-component system is activated?
A
Flagellin
15
Q
Which forms of attraction can be identified in bacteria? (5)
A
- Chemotaxis
- Phototaxis
- Aerotaxis
- Osmotaxis
- Hydrotaxis
16
Q
What are bacterial spores?
A
Survival structures to endure unfavourable growth conditions
17
Q
Why are bacterial spores resistant to many environmental influences?
A
Dormant stage -> metabolic processes cannot be disrupted
18
Q
To which factors are spores resistant? (3)
A
- Heat
- Harsh chemicals
- Radiation
19
Q
How is spore formation in bacteria triggered?
A
Two-component systems detect unfavourable conditions and activate spore-forming genes
20
Q
What is an additional advantage of spore formation to bacteria (in addition to survival)?
A
Easily dispersed via wind, water or (animal) guts
21
Q
True or false: all bacteria are capable of spore formation
A
False; only ~20 genera of Gram+ bacteria are able to do so
22
Q
How many genes are involved (approximately) in spore formation in bacteria?
A
~200
23
Q
How does the presence of maltose start transcription of maltose-related genes?
A
Maltose activates maltose activator protein, which activates RNA polymerase on the mal promotor
24
Q
What is catabolite repression?
A
A global control system in bacteria that controls the use of carbon sources if more than one is present
25
What are global control systems in bacteria?
System that regulates expression of many different genes simultaneously
26
Which carbon source do bacteria favour?
Glucose
27
What happens to bacteria in the presence of glucose?
'Glucose-effect' -> repression of lactose & maltose operons
28
Which system controls transcription in catabolite repression?
cAMP activates cAMP receptor protein (CRP), which blocks transcription maltose/lactose related genes
29
What is diauxic growth in bacteria?
Two exponential growth phases if two energy sources are available. Source one is used up first, after which the second source is used.
30
Why is there a delay between two growth phases in diauxic growth in bacteria?
Time necessary to transcribe genes needed to be able to consume another energy source
31
What is quorum sensing in bacteria?
A system by which bacteria assess population density
32
Why do bacteria use quorum sensing?
To ensure that a sufficient population density is reached before initiating certain responses
33
E. coli uses quorum sensing. Which toxin is upregulated when a quorum is reached?
O157:H17 shiga toxin
34
Which processes are activated in E. coli when a quorum is reached? (3)
1. Bacterial motility
2. Toxin production
3. Production of lesion-forming proteins
35
E. coli uses human hormones as part of its quorum sensing. Which hormones, and why?
Adrenaline/noradrenaline & AHL AI-3
Presence of human hormones notifies the bacterium that it is located intracellularly
36
In which two ways can S. aureus use autoinducing peptide (AIP) in its quorum sensing?
1. To gauge bacterial population density
2. To gauge whether it is located intracellularly (intracellularly, concentration builds up)
37
Which processes are activated by AIP in S. aureus? (2)
1. Damage to host cells
2. Alteration of the host immune system
38
Why can quorum sensing disruptors be used as drugs?
Bacteria often express virulence genes when a quorum is reached -> this can be prevented by quorum sensing disruptors
39
What is a stringent response in bacteria?
Stress response that modifies bacterial metabolism based on surroundings
40
What is an example of a stringent response in E. coli?
Voiding of E. coli reduces nutrients -> initiates production of ppGpp
41
What is an example of a stringent response in Caulobacter?
Carbon/ammonia starvation triggers production of ppGpp -> increases motile cell formation, which may reach niches with more nutrients
42
What is an example of a stringent response in mycobacteria?
Hypoxic & phostphate-limited environment of the lung produces a population of dormant persisting cells, that are also resistant to antibiotics
43
What kind of response is the heat shock response in bacteria?
Global control network
44
True or false: the heat shock response is unique to bacteria
False; this response is widespread in all domains of life
45
What is the effect of the activation of the heat shock response?
Production of heat shock proteins, which counteract damage of denatured proteins and help cells recover from temperature stress
46
Which exposures induce a heat shock response? (3)
1. Heat
2. Ethanol
3. UV-radiation
47
What is the main controller of heat shock responses in bacteria?
RpoH
48
What is the phosphate/pho regulon?
Global response network responding to evironmental phosphate concentrations
49
What is the RpoS regulon in bacteria?
Global response network that initiates a bacterial stress response
50
What is the role of RpoS in the RpoS regulon?
Master controller, controlling 400+ genes
51
Genes involved in which processes are activated by the RpoS regulon in bacteria? (4)
1. Nutrient limitation
2. Resistance to DNA damage
3. Biofilm formation
4. Responses to osmotic, oxidative & acidic stress
52
What kind of bacterium is S. pneumoniae?
Gram+ microaerophilic diplococcoid bacterium
53
In how many % of children & adults is S. pneumoniae present asymptomatically?
Children: 27-65%
Adults: <10%
54
How does S. pneumoniae spread?
Shedding of mucus
55
Which areas of the body can S. pneumoniae invade?
1. Lungs -> pneumonia
2. Bloodstream -> bacteriaemia/meningitis
3. Local invasion -> otitis media
56
How does S. pneumoniae reach the bloodstream?
Often times after invasion of the lungs
57
Why does S. pneumoniae have a so-called U-shaped curve?
Incidence is highest in young children & elderly
58
In which population does S. pneumoniae mainly cause mortality?
Elderly
59
Is the epidemiology of S. pneumoniae the same in the whole world?
Unknown; limited data from developing countries, epidemiology could be different
60
What is a common co-infection that often occurs with S. pneumoniae?
Influenza
61
Why does the epidemiology of influenza influence the epidemiology of S. pneumoniae?
Influenza infection predisposes for S. pneumoniae -> increased incidence of S. pneumoniae in case of high incidence of influenza
62
Why does influenza predispose to S. pneumoniae infection? (4)
1. Epithelial cell damage
2. Decreased mucociliary velocity
3. Reduced CCL2 expression
4. Reduced macrophage functionality
63
From which sources can S. pneumoniae be diagnosed? (4)
1. URT
2. Blood
3. Sputum
4. CSF
64
What are characteristics of S. pneumoniae cultures? (5)
1. Alpha-hemolytic
2. Shiny colonies
3. Autolytic changes -> depressed centra of bacterial colonies
4. Optochin susceptible
5. Bile solubility test
65
How does bile solubility differentiate S. pneumoniae from other streptococci?
S. pneumoniae are bile soluble, whilst other streptococci are not
66
Which other modalities (in addition to culture) can be used to diagnose S. pneumoniae? (2)
1. PCR
2. MALDI-TOF
67
What does the Griffith experiment show? What can be concluded from that?
Bacterial transformation
Shows:
1. Bacteria can transfer DNA
2. Capsules are an important virulence factor
3. Pneumococci are adept at picking up genetic material from their surrounding
68
How many serotypes of pneumococcal capsules have been identified?
~100
69
Why is the bacterial capsule a virulence factor for S. pneumoniae? (2)
1. Resistance to phagocytosis
2. Hides surface structures that lead to pathogen recognition
70
Which two pathways are involved in the synthesis of capsules? Which serotypes are produced by each pathways?
1. Synthase pathway -> serotypes 3 & 37
2. Wzx/Wzy-dependent pathway -> all other serotypes
71
How are capsule serotypes 3 & 37 bound to S. pneumoniae bacteria?
Capsule is bound to membrane
72
How are all capsule types (not 3 & 37) bound to S. pneumoniae bacteria?
Bound to peptidoglycan
73
True or false: bacterial capsules are genetically determined and cannot be influenced by surroundings
False; bacteria can adapt their capsule properties & thickness depending on surroundings
74
Which two parts can be identified in the genome of S. pneumoniae?
1. Core genome = conserved part
2. Accesory genome
75
Which two techniques are there to determine genetic variation in bacteria? (2)
1. Multi locus sequence typing
2. Whole genome sequencing
76
How can S. pneumoniae obtain accesory genes?
Horizontal gene transfer
77
What does 'competence' in bacteria mean?
Able to transfer genetic information based on environmental signals
78
Which environmental factors induce horizontal gene transfer in bacteria?
1. High cell density
2. Stress
79
Which characteristics of the URT favour natural transformation of S. pneumoniae? (2)
1. Lower temperature
2. Nutritionally challenging
80
What is the regular treatment of S. pneumoniae?
Penicillin
81
Pneumococci often contain a lot of ABC-transporters in their membrane. What are they, and what is their function?
ABC-transporter = ATP-binding casette transporters
Essential for niche adaptation through nutrient transport
82
What is pneumolysin?
Toxin produced by pneumococci
83
Which toxin do pneumococci produce?
Pneumolysin
84
What is the effect of pneumolysin?
Makes a pore in the cell membrane -> damages epithelium
85
What is the immunologically beneficial effect of pneumolysin?
Induces immune response, leading to faster clearance and decreased transmission of pneumococci
86
In which age group are pneumococcal colonization rates highest?
0-5 years
87
Which two different stages can be identified in the establishment of colonization by pneumococci? What happens during each of these stages?
1. Adherence -> expression of adherence factors & reduction of capsule thickness
2. Persistence -> increased capsule thickness
88
Production of pneumolysin leads to [higher/lower] shedding of pneumococci
Higher
89
Capsule type [does/doesn't] influence pneumococcal shedding
Capsule type does influence pneumococcal shedding
90
What is the effect of IgG on pneumococci?
Agglutination of bacteria, decreasing shedding
91
What is the effect of IgA on pneumococci?
Cleaved by pneumococcal IgA protease -> does not affect pneumococci
92
What is the effect of viral co-infection on pneumococcal shedding? (2)
1. Increased bacterial load
2. Mucus production
93
Why is invasive disease unfavourable for pneumococci?
Dead-end road -> no effective transmission
94
What are the three main reasons why S. pneumoniae is a prevalent cause of disease? (3)
1. High carriage rates
2. Genetic adaptability
3. Ability to shift from commensal to pathogenic within its host
95
What type of vaccines were the first pneumococcal vaccines?
Whole cell vaccines
96
Which two types of pneumoccoccal vaccines are currently used?
1. Polysaccharide vaccines
2. Conjugate vaccines
97
What is the main polysaccharide vaccine against S. pneumoniae?
Pneumovax
98
What do pneumococcal polysaccharide vaccines contain?
Polysaccharides of 23 most prominent serotypes
99
What is the downside of using polysaccharides in vaccines?
They are sugar structures -> cannot be presented to T-cells in MHCII, leading to a less effective immune response
100
In which population are pneumococcal polysaccharide vaccines mostly used?
Elderly
101
Why are polysaccharide vaccines not effective in children <2 years?
B-cells are immature -> incapable of mounting immune response to these vaccines
102
What do pneumococcal conjugate vaccines contain?
10/13/23 purified capsular polysaccharides, conjugated to carrier proteins that activate an immune response
103
Which carrier proteins are used in pneumococcal conjugate vaccines? (3)
1. Diphteria toxoid
2. Tetanus toxoid
3. H. influenzae protein 3
104
What is PPV23?
A 23-valent pneumococcal conjugate vaccine
105
Which adjuvant does PPV23 contain? What is its effect?
Aluminium phosphate -> activates Th2-response -> increased antibody responses by B-cell stimulation
106
How can polysaccharide-only vaccines still induce an immune response?
T-cell independent B-cell activation by crosslinking of BCR
107
What are the disadvantages of the T-cell independent activation of B-cells by polysaccharide-only vaccines? (3)
1. Weak/no induction of memory B-cells
2. Only IgM production -> not a very strong response
3. No somatic hypermutation -> no affinity maturation
108
How do conjugate vaccines induce an immune response? (3)
1. B-cells get stimulated by polysaccharides and internalize them
2. Conjugated carrier proteins are broken down and presented in MHCII by B-cells, activating Th-cells
3. Th-cells provide B-cell stimulation
109
What is the beneficial effect of the presence of T-cell help in conjugate vaccines? (3)
1. Memory formation
2. Class switch recombination
3. Somatic hypermutation
110
What is a 'correlate of protection'?
Threshold of antibody that is considered sufficient for protection
111
What is the main mechanism of protection against pneumococci after vaccination?
Osonophagocytosis
112
What are important limitations of current pneumococcal vaccines? (3)
1. Protection against a limited number of serotypes
2. Designed based on prevalence in US/EU
3. Expensive and complex to develop/manufacture
113
Current pneumococcal vaccines cover the serotypes responsible for the highest morbidity. Why is it still disadvantageous that they don't cover all serotypes?
Vaccine serotypes are replaced by serotypes not covered by the vaccine
114
Why is it a disadvantage of current pneumococcal vaccines that they are designed based on prevalence in EU/US?
Suboptimal constitution to protect against prominent serotypes in other parts of the world
115
What are important requirements of new pneumococcal vaccines? (4)
1. Broadly protective, no serotype dependency
2. Afforable
3. Targeted at infants & elderly
4. Reduces carriage and not only transmission
116
What are the two routes of administration of pneumococcal vaccines?
1. Parenteral
2. Mucosal
117
Which two types of mucosal vaccines can be used against pneumococci?
1. Intranasal
2. Oral
118
What are the advantages of using mucosal vaccines against pneumococci?
Activates MALT, leading to local and systemic immunity
119
Which are the two main immunological systems protecting against pneumococci?
1. Antibodies
2. Th17 immunity
120
What are the functions of antibodies in the defence against S. pneumoniae? (3) Which types
of antibodies are involved?
1. Opsonophagocytosis: IgG, IgA, complement
2. Blocking interaction with epithelium: IgA
3. Agglutination: IgG
121
How does IgG from the circulation reach pneumococci in mucosal surfaces?
Transcytosis by FcRs
122
Why are Th17-cells involved in defence against pneumococci?
Th17-cells are involved in defence against extracellular pathogens
123
What is the main effector mechanism of Th17-cells in pneumococcal infection?
Production of IL-17A
124
What is the effect of IL-17 secreted by Th17-cells in pneumococcal infection? (3)
1. Production of AMPs
2. Recruitment of neutrophils
3. Production of IgA
125
What are the advantages of using outer membrane vesicles in pneumococcal vaccines? (2)
1. DCs recognize both the antigen and the structure they are presented in -> vesicles induce a stronger response than loose antigens
2. OMVs contain PAMPs and can display surface antigens -> act as a combination of antigen & adjuvant
126
What are outer membrane vesicles?
Bacterial extracellular vesicles
127
What is the difficulty of using OMVs in pneumococcal vaccines? How can this be overcome?
OMVs induce a strong immune response due to high immunogenicity of LPS -> causes severe side effects
Can be overcome by detoxification of LPS
128
Which pneumococcal antigens are currently being investigated for use in pneumococcal vaccines? Why are they advantageous over polysaccharides?
Pneumocccal protein antigens -> more conserved than polysaccharides
129
How are pneumococcal protein antigens discovered?
Bacteria are cultured under conditions similar to the URT, causing them to express proteins that can be targeted
130
How many % of nosocomial infections is caused by S. aureus?
15%
131
How many % of bacteriaemia is caused by S. aureus?
25%
132
What are possible virulence factors of S. aureus? (4)
1. Panton-Valentin leucocidin (PVL)
2. TSST
3. Exfoliative toxins
4. Enterotoxins
133
What is the danger of enterotoxins?
Can act as superantigens, causing toxic shock syndrome
134
Which two main antibiotic-resistant forms of S. aureus can be identified?
1. MRSA = methyicillin-resistant S. aureus
2. VRSA = vancomycin-resistant S. aureus
135
True or false: MRSA only occurs in hospitals
False; there is now community-acquired MRSA
136
True or false: VRSA only occurs in hospitals
True
137
True or false: nasal carriers of S. aureus also have a higher carriage rate on the rest of their body
True
138
What is the age distribution pattern of nasal S. aureus colonization?
Very young children = high colonization, colonization rates decline as children age, but increase between 10-30 years old, and again decrease after 40 years of age
139
Which part of the nose is mostly colonized by S. aureus?
Vestibulum nasi -> border between skin and nose
140
How many % of people is S. aureus persistent/intermittent/non-carrier?
Persistent: 15-20%
Intermittent: 30-45%
Non-carriers: 40-50%
141
True or false: persistent S. aureus carriers often carry multiple strains
False; 98% of permanent nasal carriers only carry 1 strain
142
What are host factors that influence S. aureus colonization? (4)
1. Fasting glucose levels -> higher = higher colonization
2. Smoking -> decreases carriage rate
3. Ethnicity -> differences between groups
4. Intranasal production of AMPs
143
Which pathogen factors influence S. aureus colonization? (3)
1. Local immunosuppression by S. aureus
2. SpA levels -> positively correlated with carriage duration
3. Clumping factor B
144
What is SpA?
Staphylococcal protein A; associated with carriage of S. aureus
145
How can bacterial interference influence S. aureus colonization?
Competition with other bacterial species can reduce S. aureus carriage
146
With which bacterial species does S. aureus often compete in the nose? (2)
1. S. pneumoniae
2. S. epidermidis
