Antimicrobials: Agents, Resistance and Design Flashcards
1
Q
Define
Acquired resistance
A
occurs when a particular microorganism obtains the ability to resist the activity of an antimicrobial agent to which it was previously susceptible
2
Q
Define
ADMET
A
Initialism of absorption, distribution, metabolism, excretion, toxicity: A set of test categories used together in drug discovery to provide insight into how a pharmaceutical drug interacts with the body as a whole
3
Q
Define
Aminoglycosides
A
any of a group of antibiotics (as streptomycin and neomycin) that inhibit bacterial protein synthesis and are active especially against gram-negative bacteria
4
Q
Define
Antimicrobial agents
A
A general term for drugs, chemicals, or other substances that either kill or slow the growth of microbes
5
Q
Define
Bactericidal
A
an agent that kills bacteria
6
Q
Define
Bacteriostatic
A
an agent that prevents the growth of bacteria
7
Q
Define
β-lactamases
A
enzymes produced by bacteria that provide multi-resistance to β-lactam antibiotics such as penicillins, cephalosporins, cephamycins, and carbapenems (ertapenem),
8
Q
Define
β-lactams
A
a class of antibiotic consisting of all antibiotic agents that contain a beta-lactam ring in their molecular structures. This includes penicillin derivatives (penams), cephalosporins (cephems), monobactams, carbapenems and carbacephems
9
Q
Define
Cephalosporins
A
a large group of antibiotics derived from the mold Acremonium. They are bactericidal (kill bacteria) and work in a similar way to penicillins
10
Q
Define
Colistin
A
an antibiotic produced by certain strains of the bacteria Paenibacillus polymyxa. It is effective against most Gram-negative bacilli
11
Q
Define
Fidaxomicin
A
an oral macrolide antibiotic labeled for the treatment of Clostridium difficile–associated diarrhea in adults
12
Q
Define
Fluoroquinolones
A
any of a group of fluorinated derivatives (such as ciprofloxacin and levofloxacin) of quinolone that are used as antibacterial drugs
13
Q
Define
Forward pharmacology
A
the traditional approach to discovering new drugs. Typically, a library of chemical compounds is screened for causing a desired phenotype in cells / tissue
14
Q
Define
High-throughput screening
A
recent scientific methods relevant to the field of chemistry and biology, in which hundreds of thousands of experimental samples are subjected to simultaneous testing under given conditions
15
Q
Define
Hit to lead
A
a stage in early drug discovery where small molecule hits from a high throughput screen (HTS) are evaluated and undergo limited optimization to identify promising lead compounds
16
Q
Define
Horizontal Gene Transfer (HGT)
A
the movement of genetic material between unicellular and/or multicellular organisms other than by the (“vertical”) transmission of DNA from parent to offspring (reproduction)
17
Q
Define
In silico screening
A
Producing and screening drug candidates on a computer or via computer simulation
18
Q
Define
Intrinsic resistance
A
a natural insensitivity in bacteria that have never been susceptible to a particular antibiotic
19
Q
Define
Klebsiella pneumoniae carbapenemase (KPC)
A
a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality
20
Q
Define
Lead optimisation
A
the process by which a drug candidate is designed after an initial lead compound is identified
21
Q
Define
Macrolides
A
a class of antibiotic that includes erythromycin, roxithromycin, azithromycin and clarithromycin. They are useful in treating respiratory, skin, soft tissue, sexually transmitted, H. pylori and atypical mycobacterial infections
22
Q
Define
Mobilised colistin resistance (MCR)
A
a gene confers plasmid-mediated resistance to colistin, one of a number of last-resort antibiotics for treating Gram-negative infections
23
Q
Define
New Dehli metallo-β-lactamase
A
an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections
24
Q
Define
Nosocomial infections
A
infections that have been caught in a hospital and are potentially caused by organisms that are resistant to antibiotics
25
# Define
Omp protein
a protein involved in signal transduction. It is a highly expressed, cytoplasmic protein found in mature olfactory sensory receptor neurons of all vertebrates
26
# Define
Oxazolidinones
a novel class of synthetic antimicrobial agents unrelated to any other antibacterial drug class. They were originally developed as monoamine oxidase inhibitors for treatment of depression, with subsequent recognition of their antimicrobial properties
27
# Define
Penicillin
an antibiotic or group of antibiotics produced naturally by certain blue molds, and now usually prepared synthetically
28
# Define
Pharmacodynamics
what the drug does to the body
29
# Define
Pharmacokinetics
what the body does to the drug
30
# Define
Porin protein
beta barrel proteins that cross a cellular membrane and act as a pore, through which molecules can diffuse
31
# Define
Quinolones
a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the compound 4-quinolone
32
# Define
Resistome
a proposed expression by Gerard D. Wright for the collection of all the antibiotic resistance genes and their precursors in both pathogenic and non-pathogenic bacteria
33
# Define
Reverse pharmacology
the science of integrating documented clinical/experiential hits, into leads by transdisciplinary exploratory studies and further developing these into drug candidates by experimental and clinical research
34
# Define
Rifamycins
a natural antibiotic produced by Streptomyces mediterranei, it is a commonly used antimycobacterial drug that inhibits prokaryotic DNA-dependent RNA synthesis and protein synthesis; it blocks RNA-polymerase transcription initiation
35
# Define
Selective toxicity
refers to the ability of the drug to targets sites that are relative specific to the microorganism responsible for infection
36
# Define
Sulphonamides
a group of man-made (synthetic) medicines that contain the sulfonamide chemical group. They may also be called sulfa drugs
37
# Define
Tetracyclines
a class of antibiotics that may be used to treat infections caused by susceptible microorganisms such as gram positive and gram negative bacteria, chlamydiae, mycoplasmata, protozoans, or rickettsiae
38
# Define
Thienamycin
one of the most potent naturally produced antibiotics known thus far, was discovered in Streptomyces cattleya in 1976. It has excellent activity against both Gram-positive and Gram-negative bacteria and is resistant to bacterial β-lactamase enzymes
39
# Define
Transglycosylation
A mechanism for glycosidic (see GLYCOSIDE) bond formation, particularly during polysaccharide synthesis. Nucleoside phosphate derivatives act as activated donor compounds in which the energies of their glycosidic bonds are partially conserved in the reaction products
40
# Define
Transpeptidation
a chemical reaction (as the reversible conversion of one peptide to another by a protease) in which an amino acid residue or a peptide residue is transferred from one amino compound to another
41
# Define
Trimethoprim
an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea
42
# Define
Vancomycin
an antibiotic that when taken by mouth fights bacteria in the intestines. It is used to treat an infection of the intestines caused by Clostridium difficile, which can cause watery or bloody diarrhea
43
# Definition
occurs when a particular microorganism obtains the ability to resist the activity of an antimicrobial agent to which it was previously susceptible
Acquired resistance
44
# Definition
Initialism of absorption, distribution, metabolism, excretion, toxicity: A set of test categories used together in drug discovery to provide insight into how a pharmaceutical drug interacts with the body as a whole
ADMET
45
# Definition
any of a group of antibiotics (as streptomycin and neomycin) that inhibit bacterial protein synthesis and are active especially against gram-negative bacteria
Aminoglycosides
46
# Definition
A general term for drugs, chemicals, or other substances that either kill or slow the growth of microbes
Antimicrobial agents
47
# Definition
an agent that kills bacteria
Bactericidal
48
# Definition
an agent that prevents the growth of bacteria
Bacteriostatic
49
# Definition
enzymes produced by bacteria that provide multi-resistance to β-lactam antibiotics such as penicillins, cephalosporins, cephamycins, and carbapenems (ertapenem),
β-lactamases
50
# Definition
a class of antibiotic consisting of all antibiotic agents that contain a beta-lactam ring in their molecular structures. This includes penicillin derivatives (penams), cephalosporins (cephems), monobactams, carbapenems and carbacephems
β-lactams
51
# Definition
a large group of antibiotics derived from the mold Acremonium. They are bactericidal (kill bacteria) and work in a similar way to penicillins
Cephalosporins
52
# Definition
an antibiotic produced by certain strains of the bacteria Paenibacillus polymyxa. It is effective against most Gram-negative bacilli
Colistin
53
# Definition
an oral macrolide antibiotic labeled for the treatment of Clostridium difficile–associated diarrhea in adults
Fidaxomicin
54
# Definition
any of a group of fluorinated derivatives (such as ciprofloxacin and levofloxacin) of quinolone that are used as antibacterial drugs
Fluoroquinolones
55
# Definition
the traditional approach to discovering new drugs. Typically, a library of chemical compounds is screened for causing a desired phenotype in cells / tissue
Forward pharmacology
56
# Definition
recent scientific methods relevant to the field of chemistry and biology, in which hundreds of thousands of experimental samples are subjected to simultaneous testing under given conditions
High-throughput screening
57
# Definition
a stage in early drug discovery where small molecule hits from a high throughput screen (HTS) are evaluated and undergo limited optimization to identify promising lead compounds
Hit to lead
58
# Definition
the movement of genetic material between unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction)
Horizontal Gene Transfer (HGT)
59
# Definition
Producing and screening drug candidates on a computer or via computer simulation
In silico screening
60
# Definition
a natural insensitivity in bacteria that have never been susceptible to a particular antibiotic
Intrinsic resistance
61
# Definition
a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality
Klebsiella pneumoniae carbapenemase (KPC)
62
# Definition
the process by which a drug candidate is designed after an initial lead compound is identified
Lead optimisation
63
# Definition
a class of antibiotic that includes erythromycin, roxithromycin, azithromycin and clarithromycin. They are useful in treating respiratory, skin, soft tissue, sexually transmitted, H. pylori and atypical mycobacterial infections
Macrolides
64
# Definition
a gene confers plasmid-mediated resistance to colistin, one of a number of last-resort antibiotics for treating Gram-negative infections
Mobilised colistin resistance (MCR)
65
# Definition
an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections
New Dehli metallo-β-lactamase
66
# Definition
infections that have been caught in a hospital and are potentially caused by organisms that are resistant to antibiotics
Nosocomial infections
67
# Definition
a protein involved in signal transduction. It is a highly expressed, cytoplasmic protein found in mature olfactory sensory receptor neurons of all vertebrates
Omp protein
68
# Definition
a novel class of synthetic antimicrobial agents unrelated to any other antibacterial drug class. They were originally developed as monoamine oxidase inhibitors for treatment of depression, with subsequent recognition of their antimicrobial properties
Oxazolidinones
69
# Definition
an antibiotic or group of antibiotics produced naturally by certain blue molds, and now usually prepared synthetically
Penicillin
70
# Definition
what the drug does to the body
Pharmacodynamics
71
# Definition
what the body does to the drug
Pharmacokinetics
72
# Definition
beta barrel proteins that cross a cellular membrane and act as a pore, through which molecules can diffuse
Porin protein
73
# Definition
a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the compound 4-quinolone
Quinolones
74
# Definition
a proposed expression by Gerard D. Wright for the collection of all the antibiotic resistance genes and their precursors in both pathogenic and non-pathogenic bacteria
Resistome
75
# Definition
the science of integrating documented clinical/experiential hits, into leads by transdisciplinary exploratory studies and further developing these into drug candidates by experimental and clinical research
Reverse pharmacology
76
# Definition
a natural antibiotic produced by Streptomyces mediterranei, it is a commonly used antimycobacterial drug that inhibits prokaryotic DNA-dependent RNA synthesis and protein synthesis; it blocks RNA-polymerase transcription initiation
Rifamycins
77
# Definition
refers to the ability of the drug to targets sites that are relative specific to the microorganism responsible for infection
Selective toxicity
78
# Definition
a group of man-made (synthetic) medicines that contain the sulfonamide chemical group. They may also be called sulfa drugs
Sulphonamides
79
# Definition
a class of antibiotics that may be used to treat infections caused by susceptible microorganisms such as gram positive and gram negative bacteria, chlamydiae, mycoplasmata, protozoans, or rickettsiae
Tetracyclines
80
# Definition
one of the most potent naturally produced antibiotics known thus far, was discovered in Streptomyces cattleya in 1976. It has excellent activity against both Gram-positive and Gram-negative bacteria and is resistant to bacterial β-lactamase enzymes
Thienamycin
81
# Definition
A mechanism for glycosidic (see GLYCOSIDE) bond formation, particularly during polysaccharide synthesis. Nucleoside phosphate derivatives act as activated donor compounds in which the energies of their glycosidic bonds are partially conserved in the reaction products
Transglycosylation
82
# Definition
a chemical reaction (as the reversible conversion of one peptide to another by a protease) in which an amino acid residue or a peptide residue is transferred from one amino compound to another
Transpeptidation
83
# Definition
an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea
Trimethoprim
84
# Definition
an antibiotic that when taken by mouth fights bacteria in the intestines. It is used to treat an infection of the intestines caused by Clostridium difficile, which can cause watery or bloody diarrhea
Vancomycin
85
What are some examples of natural antimicrobial agents?
Penicillin
Aminoglycosides
Polyenes
86
What are some examples of semisynthetic antimicrobial agents?
β-lactams
Cephalosporins
87
What are some examples of synthetic antimicrobial agents?
Oxazolidinones
Quinolones
88
What is the mode of action of antibiotics?
Disruption of cell membrane funciton
Inhibition of cell wall synthesis
Inhibition of RNA and DNA synthesis
Inhibition of folic acid metabolism
Inhibition of protein sythesis
89
What is the basic monomer of peptidoglycan
A peptapeptide with D-ala D-ala at the end of the stem
90
What do Penicillin-Binding proteins (PBPs) do?
PBPs play multiple roles in cell wall synthesis and maintenance of peptidoglycan:
* transglycosylation (wall synthesis for growth and septation)
* transpeptidation (crosslinking and remodelling)
* peptide cleavage (D-Ala carboxypeptidases, endopeptidases)
* control of crosslinking, insertion of new strands
91
What is a critical part in the action of PBPs? What happens when you interupt it?
A critical part of these processes is the recognition of the D-Ala-D-Ala sequence of the MurNac-GlcNac pentapeptide. Interfering with this recognition disrupts the cell wall synthesis
92
How do β-lactams act as antibiotics (general idea)?
The β-lactam ring mimics the structure of the D-Ala-D-Ala link and bind to the same place in the PBPs (the active site), disrupting the crosslinking process.
β-lactams inactivate PBPs.
93
β-lactams are *bacteriocidal/bacteriostatic*
β-lactams are **bacteriocidal**
94
How does resistance to β-lactams occur?
Resistance occurs through production of β-lactamases or PBP and porin mutations
95
How do glycopeptide antibiotics, like Vancomycin, work?
Bind to the terminal D-Ala-D-Ala dipeptide inhibiting transglycosylation and transpeptidation of peptidoglycan.
96
Which antibiotics interfere with cell wall biosynthesis?
β-lactams
Vancomycin
97
What antibiotics inhibit protein synthesis?
Tetracyclines
Aminoglycosides
Macrolides
Oxazolidinones
98
Why can molecules that target bacterial ribosomes be used as antibiotics?
Selective toxicity due to differences in bacterial/eukaryotic ribosomes
99
What are examples of antibiotics that target the 30S subunit?
Aminoglycosides
Tetracyclines
100
What are examples of antibiotics that target the 50S subunit?
Macrolides
Oxazolidinones
101
How do tetracyclines function?
Bind to the 30S ribosomal subunit preventing entry of amino acyl-tRNA into the A-site
102
How does resistance to tetracyclines occur?
Resistance through efflux or ribosomal protection proteins
103
How do aminoglycosides funtion?
Interfere with proof-reading process for incoming aa-tRNA • Results in premature termination or proteins with amino acid substitutions
104
How does resistance to aminoglycosides occur?
Resistance through target mutations and modifying enzymes
105
How do macrolides function?
Bind reversibly to 23S rRNA in 50S subunit (peptidyl transferase domain)
Disrupt movement of tRNA from A site to P site thereby inhibiting peptide chain elongation.
106
How does resistance to macrolides occur?
Multiple resistance mechanisms
* Target modification (e.g., RNA methylation)
* Efflux
* Enzymatic modification
107
How do Oxazolidinones function?
Bind to rRNA on the A side of the peptidyltransferase center (PTC) of the ribosome
108
How does resistance to Oxazolidinones occur?
Resistance mediated through rRNA mutations
109
Which antibiotics act as inibitors of nucleic acid synthesis?
Fluoroquinolones
Rifamycins
Fidaxomicin
110
How do Fluoroquinolones function?
Bind to DNA gyrase and topoisomerases blocking formation of complex with nicked DNA
Blockage of DNA replication and DNA repair
111
How does resistance to Fluoroquinolones develop
Resistance through gyrA and gyrB mutations and through expression of gyrase-binding proteins
112
How do Rifamycins and Fidaxomicin function?
Bind to DNA-dependent RNA polymerase and block synthesis of mRNA
113
What are metabolic antagonists?
Antimicrobials that inhibit or block metabolic pathways
114
What are examples of metabolic antagonists?
Sulphonamides
Trimethoprim
115
Why are metabolic antagonists that target folic acid selective for bacteria and not human cells?
Selective because humans obtain folic acid from diet and human dihydrofolate reductase is relatively resistant to trimethoprim.
116
How do bacteria become resistant to antimicrobials?
Chromosomally-mediated resistance
Plasmid-mediated resistance
Plasmid-mediated resistance on a transposon
117
What does chromosomally-mediated resistance produce?
Chromosomal mutation can produce a drug-resistant target, which confers resistance on the bacterial cell and allows it to multiply in the presence of antibiotic.
118
How does plasmid-mediated resistance work?
Resistance genes carried on plasmids can spread from one cell to another more rapidly than cells themselves divide and spread
119
How does plasmid-mediated resistance on a transposon work?
Resistance genes on transposable genetic elements move between plasmids and the chromosome and from one plasmid to another, thereby allowing greater dissemination of the resistance gene.
120
What are the features of acquired resistance by mutation?
* Usually result in resistance to a single class of antibiotics
* Generally alters the antimicrobial target site, a modifying enzyme or an efflux system
* Cross-resistance to structurally related compounds only
121
In what ways do bacteria modify the antibiotic molecule?
1. Inactivate the drug by chemically cleaving it
2. Inactivate the drug by adding chemical moieties.
122
How do β-lactamases confer resistance?
Inactivate the drug by chemically cleaving it
123
How do aminoglycoside modifying enzymes confer resistance?
Inactivate the drug by adding chemical moieties.
124
In what ways can modified antibiotic transport confer resistance?
Decreased cell wall pemeability
Increased efflux from the cell
125
How does decreased cell wall permeability prevent the action of some antibiotics?
Altered porin or Omp proteins lead to decreased uptake of βlactam antibiotics in Klebsiella pneumoniae and Pseudomonas aeruginosa.
126
How does modification of the target site confer resistance?
Alteration of the target site to reduce susceptibility to antibiotic
Acquisition of genes encoding enzymes that alter target
127
What does Vancomycin resistance involve?
Vancomycin resistance involves acquisition of genes encoding enzymes that alter the D-Ala-D-Ala to D-Ala-D-Lac, reducing the binding of the vancomycin drug.
128
How do we treat patients with resistant Gram-negative infections?
The β-lactams were the ‘golden bullet’ for a long time for infections with Gram-negative pathogens
Other current options for treatment include
* Tigecycline (tetracycline derivative)
* Colistin (also known as polymyxin E)
Not well suited to serious infections (poor pharmacokinetic profiles)
* Polymixins have side effects including kidney and neurotoxicity
* Tetracyclines have gastrointestinal side effect
129
Efflux pump mechanism
130
Aminoglycoside-modifying enzymes act to change the chemical structure of the aminoglycoside, preventing it from binding to its target.
Select one:
True
False
Aminoglycoside-modifying enzymes act to change the chemical structure of the aminoglycoside, preventing it from binding to its target.
Select one:
**True**
False
131
The major role of penicillin-binding proteins in bacterial cells is to
Select one:
a. bind penicillin and thereby confer penicillin resistance.
b. crosslink peptidoglycan strands by catalyzing transpeptidation.
c. bind penicillin and thereby block protein biosynthesis.
d. act as an essential co-factor in protein biosynthesis.
The major role of penicillin-binding proteins in bacterial cells is to
Select one:
a. bind penicillin and thereby confer penicillin resistance.
**b. crosslink peptidoglycan strands by catalyzing transpeptidation.**
c. bind penicillin and thereby block protein biosynthesis.
d. act as an essential co-factor in protein biosynthesis.
132
The structure below is a cell wall from which microorganism?
Fungus
133
Beta-lactamases are a diverse set of enzymes that can inactivate many different types of beta-lactam antibiotics.
Select one:
True
False
Beta-lactamases are a diverse set of enzymes that can inactivate many different types of beta-lactam antibiotics.
Select one:
**True**
False
134
Which of the following is the major reason why it has been difficult to treat viral infections with chemotherapeutic agents?
Select one:
a. Viral metabolism resembles that of their hosts so there is no selective point of attack.
b. Viruses use the metabolic machinery of their hosts, which limits many of the potential points of attack.
c. Viruses have no metabolism and therefore offer no selective point of attack.
d. Actually, viruses are not difficult to treat with chemotherapeutic agents.
Which of the following is the major reason why it has been difficult to treat viral infections with chemotherapeutic agents?
Select one:
a. Viral metabolism resembles that of their hosts so there is no selective point of attack.
**b. Viruses use the metabolic machinery of their hosts, which limits many of the potential points of attack.**
c. Viruses have no metabolism and therefore offer no selective point of attack.
d. Actually, viruses are not difficult to treat with chemotherapeutic agents.
135
A single mutation to a gene can be enough to induce resistance.
Select one:
True
False
A single mutation to a gene can be enough to induce resistance.
Select one:
**True**
False
136
Peptidoglycan synthesis inhibitors often induce bacterial lysis, while protein synthesis inhibitors do not. Beta-lactam antibiotics (e.g. penicillin, cefoxitin) cause bacterial lysis because:
Select one:
a. They block the ribosomal exit tunnel
b. They disrupt cell wall biosynthesis
c. They induce DNA breaks
d. They induce the synthesis of aberrant proteins
Peptidoglycan synthesis inhibitors often induce bacterial lysis, while protein synthesis inhibitors do not. Beta-lactam antibiotics (e.g. penicillin, cefoxitin) cause bacterial lysis because:
Select one:
a. They block the ribosomal exit tunnel
**b. They disrupt cell wall biosynthesis**
c. They induce DNA breaks
d. They induce the synthesis of aberrant proteins
137
The mechanisms that resistant bacteria can use to generate a resistant phenotype include
Select one:
a. Modification of the drug target, drug transport or drug itself
b. The acquisition of resistance genes
c. Horizontal gene transfer of plasmids containing transposons.
d. Spontaneous mutation of the chromosome
The mechanisms that resistant bacteria can use to generate a resistant phenotype include
Select one:
**a. Modification of the drug target, drug transport or drug itself**
b. The acquisition of resistance genes
c. Horizontal gene transfer of plasmids containing transposons.
d. Spontaneous mutation of the chromosome
138
HOW DO I MEDIATE RESISTANCE? I alter the sequence of the D-Ala-D-Ala sequence of the MurNac-GlcNac pentapeptide to D-Ala-D-Lac?
Alteration of the antibiotic target. Vancomycin resistance is mediated by the acquisition of genes that encode enzymes that change the target of vancomycin (D-Ala-D-Ala of the starting pentapeptide of peptidoglycan). This reduces the ability of vancomycin to bind and act.
139
Which of the following is a desirable general characteristic of antimicrobial drugs?
Select one:
a. Selective toxicity
b. Broad-spectrum of activity
c. Bactericidal rather than bacteriostatic
d. All of the choices are correct.
Which of the following is a desirable general characteristic of antimicrobial drugs?
Select one:
a. Selective toxicity
b. Broad-spectrum of activity
c. Bactericidal rather than bacteriostatic
**d. All of the choices are correct.**
140
The blaKPC gene encodes resistance to carbapenems.
Select one:
True
False
The blaKPC gene encodes resistance to carbapenems.
Select one:
**True**
False
141
MCR-1 refers to the protein the encodes resistance to the polymyxins.
Select one:
True
False
MCR-1 refers to the protein the encodes resistance to the polymyxins.
Select one:
**True**
False
142
As long as the antibiotic can get inside the bacteria (through the cell wall and membrane), it will be active.
Select one:
True
False
As long as the antibiotic can get inside the bacteria (through the cell wall and membrane), it will be active.
Select one:
True
**False**
143
Which of the following is likely to have the most toxic side effects to humans?
Select one:
a. Inhibitors of cell wall synthesis
b. Inhibitors of protein synthesis
c. Disrupters of cell membrane structure
d. Inhibitors of DNA synthesis
Which of the following is likely to have the most toxic side effects to humans?
Select one:
a. Inhibitors of cell wall synthesis
b. Inhibitors of protein synthesis
**c. Disrupters of cell membrane structure**
d. Inhibitors of DNA synthesis
144
If you come into contact with a multi-drug resistant bacteria, you will probably die.
Select one:
True
False
If you come into contact with a multi-drug resistant bacteria, you will probably die.
Select one:
True
**False**
145
Transposable genetic elements can move between plasmids and chromosomes and from one plasmid to another, thereby allowing greater dissemination of the resistance gene?
Select one:
True
False
Transposable genetic elements can move between plasmids and chromosomes and from one plasmid to another, thereby allowing greater dissemination of the resistance gene?
Select one:
**True**
False
146
Protein synthesis inhibitors generally do not result in bacterial lysis, while peptidoglycan synthesis inhibitors do. Aminoglycoside antibiotics (e.g. Streptomycin, Kanamycin) cause bacterial death because:
Select one:
a. They block the ribosomal exit tunnel
b. They disrupt cell wall biosynthesis
c. The induce DNA breaks
d. The induce the synthesis of aberrant proteins
Protein synthesis inhibitors generally do not result in bacterial lysis, while peptidoglycan synthesis inhibitors do. Aminoglycoside antibiotics (e.g. Streptomycin, Kanamycin) cause bacterial death because:
Select one:
a. They block the ribosomal exit tunnel
b. They disrupt cell wall biosynthesis
c. The induce DNA breaks
**d. The induce the synthesis of aberrant proteins**
147
Generally, a bacterium only has one resistance mechanism per antibiotic.
Select one:
True
False
Generally, a bacterium only has one resistance mechanism per antibiotic.
Select one:
True
**False**
148
Resistance by mutation is a rare event and therefore is not a concern for antibiotic resistance.
Select one:
True
False
Resistance by mutation is a rare event and therefore is not a concern for antibiotic resistance.
Select one:
True
**False**
149
WHO AM I? I am a major cause for concern for Gram negative pathogens. I am an enzyme and can cleave the beta-lactam ring in beta-lactam antibiotics. I have lots of friends and family spread around the world. I can be found in the chromosome, on plasmids and transposons. There are over 1000 different classes of me.
beta-lactamases
150
Bacteria only become drug resistant due to incorrect usage of antibiotics?
Select one:
True
False
Bacteria only become drug resistant due to incorrect usage of antibiotics?
Select one:
True
**False**
151
WHO AM I? I am a resistance-mediating enzyme. I alter the target binding site of the macrolide antibiotics by methylating a residue in the 23S RNA of the 50S ribosomal subunit. There are at least 30 different classes of me.
The erythromycin ribosomal mediating (Erm) enzyme
152
What is a hit?
A “hit” candidate is an active substance that has the desired antimicrobial action on the microbe or in a disease model.
153
Where do you find hits?
Start with the natural substrate and produce a derivative.
Screening libraries (‘000s to 000’000s of candidates)
154
How do you identify a “hit” in a library?
1) High-throughput screening
2) Medium throughput screening
3) In silico (computational) screening
155
What are the advantages of High-throughput screening?
* Automated (high speed + low running cost)
* Small volumes (less reagents = cheaper)
* Screen millions of compounds if desired
* Broad applicability (can do many different types of assays)
156
What are the disadvantages of High-throughput screening?
* Expensive infrastructure
* Can be difficult to optimize (translation of complex assays from lab to a robot set-up can be hard to achieve)
* Can have high rate of false positives
157
What are the advantages of Medium throughput screening?
* Semi-automated (speed + low running cost)
* Cheaper set up (can be laboratory-based)
* Broader applicability (can do many different types of assays)
* Can get more data from single assay
* Less false positives
158
What are the disadvantages of Medium throughput screening?
* Limited number of samples
* Larger volumes (more regents required)
159
What are the advantages of In silico (computational) screening?
* Cost
* Speed
* (Apparent) higher hit rate
160
What are the disadvantages of In silico (computational) screening?
* Requires drug target is known and extensively characterised (structure & mechanism)
* In reality, false positive ‘hits’ are very high
* Requires a very high level of understanding of protein chemistry
* Must be experimentally validated
161
What do you do once a hit candidate has been identified?
* Identify the active substance / chemical composition of the “hit”.
* In vitro production or commercial supply of hit.
* Re-test hit in a dose-response assay and confirm activity.
162
What is the focus of hit to lead optimisation?
The focus of the hit to lead optimisation is:
1. Solubility of the candidate.
2. ADMET (Adsorption, Disposition, Metabolism, Excretion and Toxicity).
3. Ensuring minimal or no ‘off-target effects’.
163
What is drug design?
Select one:
a. The inventive process of finding new medicines.
b. The process by which existing drugs are improved.
c. The process by which all antimicrobials are made.
d. The process of finding active pharmaceutical compounds by trial and error.
What is drug design?
Select one:
**a. The inventive process of finding new medicines.**
b. The process by which existing drugs are improved.
c. The process by which all antimicrobials are made.
d. The process of finding active pharmaceutical compounds by trial and error.
164
X-ray crystal structures can
Select one:
a. Slow the drug discovery process because crystal structures are hard and slow to finish.
b. Speed up the process of hit candidate optimisation by improving structure-activity relationships.
c. Speed up the process of lead candidate optimisation by improving drug-like properties.
d. Stop a drug discovery project if a crystal structure cannot be determined.
X-ray crystal structures can
Select one:
a. Slow the drug discovery process because crystal structures are hard and slow to finish.
**b. Speed up the process of hit candidate optimisation by improving structure-activity relationships.**
c. Speed up the process of lead candidate optimisation by improving drug-like properties.
d. Stop a drug discovery project if a crystal structure cannot be determined.
165
The aim of hit-to-lead optimisation is
Select one:
a. To find an active substance that has desired anti-microbial action.
b. To optimise an active substance to be more potent.
c. To improve the potency of an active substance.
d. To optimise an active substance to retain potency and have desirable drug-like properties.
The aim of hit-to-lead optimisation is
Select one:
a. To find an active substance that has desired anti-microbial action.
b. To optimise an active substance to be more potent.
c. To improve the potency of an active substance.
**d. To optimise an active substance to retain potency and have desirable drug-like properties.**
166
Which of the following best describe the scientific disciplines required for early antimicrobial drug discovery?
Select one:
a. Microbiology / biochemistry, chemistry / medicinal chemistry, structural biology.
b. Microbiology, chemistry, bioinformatics, structural biology.
c. Chemistry / medicinal chemistry, structural biology.
d. Biochemistry and Pharmacology.
Which of the following best describe the scientific disciplines required for early antimicrobial drug discovery?
Select one:
**a. Microbiology / biochemistry, chemistry / medicinal chemistry, structural biology.**
b. Microbiology, chemistry, bioinformatics, structural biology.
c. Chemistry / medicinal chemistry, structural biology.
d. Biochemistry and Pharmacology.
167
What are the essential requirements starting a new drug discovery project with a drug target
Select one:
a. A complete understanding of the role of the target within the microbe physiology.
b. Target identification, in vitro production and a robust assay to assess the target activity.
c. Target identification, the mechanism of action and the structure of the target.
d. Target identification, the mechanism of action and a robust assay to assess the target activity.
What are the essential requirements starting a new drug discovery project with a drug target
Select one:
a. A complete understanding of the role of the target within the microbe physiology.
**b. Target identification, in vitro production and a robust assay to assess the target activity.**
c. Target identification, the mechanism of action and the structure of the target.
d. Target identification, the mechanism of action and a robust assay to assess the target activity.
168
TRUE OR FALSE? One Health refers to the collaborative effort of multiple disciplines – working locally, nationally and globally – to attain optimal health for people, animals and the environment.
Select one:
True
False
TRUE OR FALSE? One Health refers to the collaborative effort of multiple disciplines – working locally, nationally and globally – to attain optimal health for people, animals and the environment.
Select one:
**True**
False
169
TRUE or FALSE? Antibiotic use in animal husbandry represents one of the greatest challenges for antibiotic control and stewardship.
Select one:
True
False
TRUE or FALSE? Antibiotic use in animal husbandry represents one of the greatest challenges for antibiotic control and stewardship.
Select one:
**True**
False
170
TRUE or FALSE? Treating cancer patients will become more difficult in the absence of effective antibiotics.
Select one:
True
False
TRUE or FALSE? Treating cancer patients will become more difficult in the absence of effective antibiotics.
Select one:
**True**
False
171
TRUE or FALSE? Rapid and accurate, point of care, diagnostics are vital to control ‘superbugs’.
Select one:
True
False
TRUE or FALSE? Rapid and accurate, point of care, diagnostics are vital to control ‘superbugs’.
Select one:
**True**
False
172
TRUE or FALSE? Education is an essential part of antibiotic stewardship.
Select one:
True
False
TRUE or FALSE? Education is an essential part of antibiotic stewardship.
Select one:
**True**
False
173
The animal microbiome can (select all correct answers)
Select one or more:
a. exchange with farm workers who can then exchange with their friends, family and co-workers.
b. can be readily exchanged by eating animal meat
c. can contaminate vegetables
d. can acquire resistance genes from soil microbiome
e. only acquires resistance from over-use of antibiotics
f. can only effect other animals
The animal microbiome can (select all correct answers)
Select one or more:
**a. exchange with farm workers who can then exchange with their friends, family and co-workers.**
b. can be readily exchanged by eating animal meat
**c. can contaminate vegetables**
**d. can acquire resistance genes from soil microbiome**
e. only acquires resistance from over-use of antibiotics
f. can only effect other animals
174
The advantages of high-throughput screening for drug discovery are that the process is
Select one:
a. fully automated, accepts different assay types and can screen millions of compounds.
b. semi-automated, accepts different assay types and can screen thousands of compounds.
c. semi-automated and the screening is performed on computers
d. fully automated, accepts different assay types and has a low rate of false positives hits.
The advantages of high-throughput screening for drug discovery are that the process is
Select one:
**a. fully automated, accepts different assay types and can screen millions of compounds.**
b. semi-automated, accepts different assay types and can screen thousands of compounds.
c. semi-automated and the screening is performed on computers
d. fully automated, accepts different assay types and has a low rate of false positives hits.
175
# Define
Acellular vaccines
A vaccine that may contain cellular material but does not contain complete cells
176
# Define
Acquired immunity
Immunity acquired by infection or vaccination (active immunity) or by the transfer of antibody or lymphocytes from an immune donor (passive immunity)
177
# Define
Active immunity
the immunity which results from the production of antibodies by the immune system in response to the presence of an antigen
178
# Define
Adjuvant
a substance which enhances the body's immune response to an antigen.
179
# Define
Alum
the classical adjuvant most often used in vaccines in humans, includes a range of salts of aluminum precipitated under basic conditions, usually aluminum sulfate mixed with sodium or potassium hydroxide plus a variable amount of phosphate.
180
# Define
Antigen
a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies
181
# Define
Damage associated molecular patterns (DAMPs)
molecules released by stressed cells undergoing necrosis that act as endogenous danger signals to promote and exacerbate the inflammatory response
182
# Define
DTaP
a vaccine that helps children younger than age 7 develop immunity to three deadly diseases caused by bacteria: diphtheria, tetanus, and whooping cough (pertussis)
183
# Define
DTwP
a mixture of the detoxified toxins (toxoids) of diphtheria and tetanus and inactivated Bordetella pertussis that have been adsorbed onto an aluminum salt
184
# Define
Efficacy
the percentage reduction of disease in a vaccinated group of people compared to an unvaccinated group, using the most favorable conditions
185
# Define
Herd immunity
a form of indirect protection from infectious disease that occurs when a large percentage of a population has become immune to an infection, thereby providing a measure of protection for individuals who are not immune
186
# Define
Killed inactivate vaccines
a vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then lose disease producing capacity
187
# Define
Live attenuated vaccines
a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live")
188
# Define
Measles
a highly contagious infectious disease caused by the measles virus
189
# Define
Nanopatches
a needle-free vaccine delivery device
190
# Define
Opsonise
make (a foreign cell) more susceptible to phagocytosis
191
# Define
Passive immunity
the short-term immunity which results from the introduction of antibodies from another person or animal
192
# Define
Recombinant vaccines
a vaccine produced through recombinant DNA technology
193
# Define
Reservoir
is the population of organisms or the specific environment in which an infectious pathogen naturally lives and reproduces, or upon which the pathogen primarily depends for its survival
194
# Define
Subunit vaccines
a fragment of a pathogen, typically a surface protein, that is used to trigger an immune response and stimulate acquired immunity against the pathogen from which it is derived
195
# Define
The Cutter Incident
one of the worst pharmaceutical disasters in US history, and exposed several thousand children to live polio virus on vaccination
196
# Define
Toxoid vaccines
A vaccine made from a toxin (poison) that has been made harmless but that elicits an immune response against the toxin
197
# Define
Tropism
the turning of all or part of an organism in a particular direction in response to an external stimulus
198
# Define
Variolation
the method first used to immunize an individual against smallpox (Variola) with material taken from a patient or a recently variolated individual, in the hope that a mild, but protective, infection would result
199
# Definition
A vaccine that may contain cellular material but does not contain complete cells
Acellular vaccines
200
# Definition
Immunity acquired by infection or vaccination (active immunity) or by the transfer of antibody or lymphocytes from an immune donor (passive immunity)
Acquired immunity
201
# Definition
the immunity which results from the production of antibodies by the immune system in response to the presence of an antigen
Active immunity
202
# Definition
a substance which enhances the body's immune response to an antigen.
Adjuvant
203
# Definition
the classical adjuvant most often used in vaccines in humans, includes a range of salts of aluminum precipitated under basic conditions, usually aluminum sulfate mixed with sodium or potassium hydroxide plus a variable amount of phosphate.
Alum
204
# Definition
a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies
Antigen
205
# Definition
molecules released by stressed cells undergoing necrosis that act as endogenous danger signals to promote and exacerbate the inflammatory response
Damage associated molecular patterns (DAMPs)
206
# Definition
a vaccine that helps children younger than age 7 develop immunity to three deadly diseases caused by bacteria: diphtheria, tetanus, and whooping cough (pertussis)
DTaP
207
# Definition
a mixture of the detoxified toxins (toxoids) of diphtheria and tetanus and inactivated Bordetella pertussis that have been adsorbed onto an aluminum salt
DTwP
208
# Definition
the percentage reduction of disease in a vaccinated group of people compared to an unvaccinated group, using the most favorable conditions
Efficacy
209
# Definition
a form of indirect protection from infectious disease that occurs when a large percentage of a population has become immune to an infection, thereby providing a measure of protection for individuals who are not immune
Herd immunity
210
# Definition
a vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then lose disease producing capacity
Killed inactivate vaccines
211
# Definition
a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live")
Live attenuated vaccines
212
# Definition
a highly contagious infectious disease caused by the measles virus
Measles
213
# Definition
a needle-free vaccine delivery device
Nanopatches
214
# Definition
make (a foreign cell) more susceptible to phagocytosis
Opsonise
215
# Definition
the short-term immunity which results from the introduction of antibodies from another person or animal
Passive immunity
216
# Definition
a vaccine produced through recombinant DNA technology
Recombinant vaccines
217
# Definition
is the population of organisms or the specific environment in which an infectious pathogen naturally lives and reproduces, or upon which the pathogen primarily depends for its survival
Reservoir
218
# Definition
a fragment of a pathogen, typically a surface protein, that is used to trigger an immune response and stimulate acquired immunity against the pathogen from which it is derived
Subunit vaccines
219
# Definition
one of the worst pharmaceutical disasters in US history, and exposed several thousand children to live polio virus on vaccination
The Cutter Incident
220
# Definition
A vaccine made from a toxin (poison) that has been made harmless but that elicits an immune response against the toxin
Toxoid vaccines
221
# Definition
the turning of all or part of an organism in a particular direction in response to an external stimulus
Tropism
222
# Definition
the method first used to immunize an individual against smallpox (Variola) with material taken from a patient or a recently variolated individual, in the hope that a mild, but protective, infection would result
Variolation
223
What is the first main barrier to infectious agents?
Skin
224
Which three main types of leukocytes are there?
Lymphocytes
APCs
Innate cells (NK, neutrophils etc.)
225
What does immunological memory require?
Innate immune responses
Antigen uptake and presentation to trigger
Adaptive immune responses (B and T cells)
226
What does vaccination and immunological memory do to the number of B or T cells that recognise a specific antigen?
Increases the number of B or T cells that recognise a specific antigen
227
What does vaccination and immunological memory do to the amount of signal needed to activate antigen-specific memory B and T cells?
Decreases the amount of signal needed to activate antigen-specific memory B and T cells
228
What are the two types of acquired immunity?
Active and Passive
229
What is passive immunisation good for?
* Toxins: snake bites, tetanus, rabies, gas gangrene
* Outbreaks where antibody can provide protection to survivors but vaccines are not developed
230
Passive immunisation is ideally given *before/after* infection
Passive immunisation is ideally given **before** infection
231
Passive immunisation provides *delayed/immediate* onset of protection
Passive immunisation provides **immediate** onset of protection
232
Passive immunisation is *long-lasting/limited*
Passive immunisation is **limited**
233
Active immunisation is ideally given *before/after* infection
Active immunisation is ideally given **before** infection
234
Active immunisation protection is *delayed/immediate*
Active immunisation protection is **delayed**
235
What is active immunisation good for?
* Inducing widespread immunity in the community to highly transmissible diseases
* Influenza, measles, HPV
236
What is the ultimate aim of vaccination? What are the secondary aims?
Eradication of disease from population
* Prevent infection
* Reduce infectious load/severity
* Reduce infection transmission
237
What is the major limit of herd immunity?
Herd immunity only applies for diseases that spread from human to human
238
\_\_\_\_\_\_\_\_\_\_\_: a compound that triggers innate immunity
\_\_\_\_\_\_\_\_\_\_\_: a component of the virus, bacteria or parasite that is immunogenic
**Adjuvant**: a compound that triggers innate immunity
**Antigen**: a component of the virus, bacteria or parasite that is immunogenic
239
What are the criteria for selecting suitable antigens?
1. Abundantly expressed and accessible to protective immune mechanisms:
* Expressed on the pathogen surface or a secreted toxin if antibody‐mediated immunity provides protection
* Expressed on infected cells if T cell‐mediated immunity provides protection
2. Does not vary:
* Some pathogens can mutate antigens if immune responses are directed against those antigens (HIV, influenza, etc.)
* Some pathogens change antigens during their natural lifecycle (malaria, TB, etc.)
* Therefore, choose an antigen which is essential to critical life stages of the pathogen
240
Why do viruses live HIV-1 ungergo extremely rapid rates of mutation?
RNA polymerase doesn't proofread
241
How do you combat the increadible diversity of HIV in order to make a vaccine?
* Env is the most abundant antigen on the virus surface and it mutates at incredibly high rate
* BUT certain sites on Env must be conserved to enable virus binding and entry to infect cells‐ the “CD4 binding site”
* We can make antibodies for the CD4 binding site that neutralise a diverse array of HIV‐1 viruses:
* Use in passive immunisation We can focus the immune response on the CD4 binding site:
* Vaccinate with the CD4 binding site alone as our antigen
242
What does a good adjuvant do?
1. Increases the magnitude of the adaptive immune response
2. Shapes the type of adaptive immune response (antibody isotype, CD4+ T cell subset, CD8+ T cells)
243
How do adjuvants augment the immune response?
1. Trigger innate immunity
2. Promote uptake of antigen by DCs
244
What are some examples of PRRs that recognise PAMPs and DAMPs?
TLR
RLR
CLR
NLR
245
What do PRRs bind to?
PAMPs
DAMPs
246
What molecules are usually used as adjuvants?
PAMPs or induced DAMPs
247
What do you need to consider about adjuvant that you choose?
What branch of the immune system does it fire up
Each PAMP/DAMP elicits a different set of innate cytokines, which acts on B cell and T cells to skew the immune system in distinct directions:
i.e. IL‐12 + IFN‐γ= IgG2a antibody, Th1 CD4 T cells and CD8 T cells
248
Which adjuvant triggers innate immunity and promotes antigen uptake?
Alum
249
True or False:
Only one adjuvant can be used per vaccine
False
There can be synergy when adjuvants are combined‐ RTS’S (Malaria) and Shingrix (Shingles)
250
What are the three main considerations when designing a vaccine?
Route of delivery
Adjuvant
Antigen
251
What are the four phases for the clincial testing of vaccines?
Phase I: Safety
Phase II: Immunogenicity (and Safety)
Phase III: Immunogenicity, Feasibility (and Safety)
Phase IV: Post‐approval monitoring (i.e. Safety)
252
What are the potential side-effects of vaccines?
* Swelling at vaccine site, fever, muscle aches, fatigue: activation of innate immunity causes immune cell recruitment and pyrexia, etc
* Anaphylaxis: some vaccines are cultured in eggs or yeast expression systems (15 min wait after vaccination)
* Seizures in children: due to vaccine‐induced innate immunity causing fevers. Similar to infection‐induced febrile seizures.
* Guillian‐Barré syndrome: due to vaccine‐induced innate immunity triggering auto‐immunity. Can also be induced by infections.
253
What are the three types of vaccines?
Live attenuated vaccines
Killed inactivated vaccines
Subunit vaccines
254
What does attentuated mean?
passage through cell culture or use of genetic techniques to induce mutations that remove virulence but retain immunogenicity
255
How are pathogens killed to created killed inactivated viruses
Uses chemical (formalin or phenol treatment) or heat inactivation to kill pathogen, which is then used in the vaccine, sometimes with an additional adjuvant
256
What was initially used to prevent Smallpox?
Variolation
257
Why was Smallpox successfully eradicated?
* A stable, cheap, very efficacious (90‐97%) vaccine available
* The reservoir was limited:
* Only infects humans (no animal reservoir)
* Infected died or resolved infection (no chronic infection)
* Infection was easily recognised (isolate the infected)
* Only 2 viral variants (variola major and variola minor)
* Intensive, co‐ordinated, global surveillance‐ ring vaccination
258
What is the name of the activated vaccine used to treat polio? What were the negatives?
Trivalent Oral polio vaccine (tOPV)
* Developed by Albert Sabin (1963)
* Live attenuated vaccine (3 strains)
* Very effective at inducing immunity
* Easy to administer (oral)
* But it can:
* Revert to virulent virus
* Cause vaccine‐induced paralysis
259
What is the name of the inactivated Polio vaccine? What is its negatives?
Trivalent Inactivated Polio Vaccine (tIPV)
* Developed by Jonas Salk (1955)
* Inactivated vaccine (3 strains)
* Virus is formalin inactivated
* Not as effective at inducing immunity
* Have to inject the vaccine
260
Why did the Cutter Incident occur?
* Inexperience at lab
* Lack of federal regulation
261
What is the name of the inactivated Pertussis vaccine? What are its negatives?
First vaccine was known as the “whole cell” vaccine (DTwP)
* Formulated with diphtheria and tetanus toxins
* Inactivated vaccine
* Treat bacteria formalin to inactivate the bacteria and toxin
* Adjuvanted with alum
* Issues with reactogenicity‐ high rate of fevers and seizures
262
What is the name of the acellular subunit Pertussis vaccine? What is its negatives?
New pertussis vaccine is known as the “acellular” vaccine (DTaP)
* Subunit vaccine
* 3‐5 purified pertussis antigens, including the inactivated toxin
* Alum adjuvant
* Much less reactogenic but immunity is less effective and wanes quickly, so an adolescent boost (TdaP) was added:
263
How do you make a recombinant vaccine?
* Identify antigen of interest
* Clone the gene coding that antigen into an expression system that grows, produces protein at a high rate (i.e. yeast)
* Purify the protein antigen
264
What are the differences between polysaccharide-only and conjugate vaccines?
* Bacterial capsules made of polysaccharide are targets for antibody
* But polysaccharide isn’t immunogenic for T cells:
* Polysaccharide‐only vaccines lack CD4 T cell help for B cell responses and immunity is weak and short‐lived
* Conjugate polysaccharide to immunogenic protein (i.e toxoid):
* In conjugate vaccines, a CD4 T cell response to the protein provides “help” for the B cell response to the polysaccharide
265
What are the pros and cons of Live Attenuated vaccines?
**Pros:**
* Induces strong life-long immunity for antibody and T-cells
**Cons:**
* Can cause more severe side-effects
* Can cause disease in immunocompromised people
* Chance of reversion of virulence
266
What are the Pros and Cons of Killed Inactivated vaccines?
**Pros:**
* Can induce strong, long-lasting immunity
**Cons:**
* Reliant on effective inactivation
* Can be more reactogenic
267
What are the Pros and Cons of Subunit vaccines?
**Pros:**
* Very safe
* Can induce antibody immunity
**Cons:**
* Not good for T-cell imunity
* Immunity may wane or be less effective at preventing infection
* Requires multiple shots
268
How are viral vector vaccines made?
Take a harmful pathogen:
* Identify gene for a target antigen
Take a minimally pathogenic virus:
* Remove genetic material associated with virulence
* Insert target antigen
Infects cells like vector virus:
* Not virulent
* Expresses target antigen
269
What is the antigen for viral vector vaccines?
inserted gene that encodes the required protein
270
What is the adjuvant for viral vector vaccines?
viral particle increases uptake, several viral danger signals (dsRNA‐ TLR3; ssDNA‐ TLR7; etc)
271
What are the advantages of viral vector vaccines?
* Very safe
* Quick and cheap to make (pandemic situations)
* Mimics a “live” infection more closely because it combines mechanisms of adjuvancy
272
What are the disadvantages of viral vector vaccines?
Pre‐existing immunity to the virus used as the vector may limit immune responses
273
Which viral vector was used to make the ebola vaccine?
Vesicular stomatis virus (VSV)
274
What does attentuation remove and what does it retain?
Remove: Virulence factors
Retain: Infectivity
275
Name one eradicated pathogen
Smallpox
276
Name one near-eradicated pathogen
Polio
