Module 7 - Epidemiology, Antibiotics and Antibiotic Resistance

Question 1

Distinguish between Endemic, Epidemic and Pandemic disease

Answer 1

Endemic = Constantly present, low level frequency of disease at regular intervals
Epidemic = Sudden increase above expected level, each individual infects more than 1 other susceptible host
Pandemic = simultaneous increase over wide/global area

Question 2

Name the disease that is responsible for the amphibian decline, and what kind of outbreak/disease is this?

Answer 2

Chytridiomycosis (panzootic -> animal pandemic)

Question 3

Name 6 pandemic plant diseases

Answer 3

Maize Lethal Necrosis
Rice tungro
Sweet potato virus
Banana bunchy top
Citrus Tristeza Virus
Plum Pox

Question 4

Name the two parameters for measuring disease rate (and define these)

Answer 4

Morbidity rate -> number of individuals becoming ill
Mortality rate -> rate of death from disease

Question 5

What number is sometimes used as the threshold to define epidemics?

Answer 5

400 cases per 100,000 population per week

Question 6

What are the two types of epidemics? (And define them)

Answer 6

Common source epidemic -> sharp rise to a peak and rapid decline (e.g., food poisoning)
Propagated epidemic -> slow rise and gradual decline

Question 7

Approximately what percentage of population immunity is required to prevent the spread of measles, flu and polio respectively?

Answer 7

Measles: 90-95%
Flu: 90%
Polio: 70%

Question 8

What is the approximate susceptible population size required to sustain measles in a community?

Answer 8

250,000 - 300,000

Question 9

What are the two main sources of change in organisms that can render immunity ineffective?

Answer 9

Antigenic drift and antigenic SHIFT

Question 10

Define antigenic drift

Answer 10

Minor antigenic variation -> Haemagglutanin or Neuraminidase can change due to genetic mutations altering amino acid sequences

Question 11

Define Antigenic Shift

Answer 11

More significant antigenic variation -> reassortment of segments of genome due to gene exchange between strains

Question 12

What four main things do epidemiologists investigate to understand disease?

Answer 12

The pathogen
The source of the pathogen
Reservoirs and Carriers
Transmission of Pathogens (e.g., airborne/contact/vector)

Question 13

What are the three main types of disease control measure?

Answer 13

Eliminate source
Break connection between source and host
Raise level of herd immunity (vaccinate)

Question 14

What genus of virus causes Zika (also genome type)

Answer 14

Flavivirus (ssRNA)

Question 15

How is Zika virus transmitted?

Answer 15

Mosquito, Sexually, Blood Transfusion, in utero

Question 16

What are some of the main factors responsible for emergence of new pathogens and re-emergence of known pathogens?

Answer 16

Demographics (e.g., cities)
Transportation (^ speed of spread)
Economic development + Changes in Land Use
International Travel
Microbial Adaptation
Biological Warfare
Breakdown of Public Health Measures

Question 17

Name the organism that causes the Black Death

Answer 17

Yersinia pestis

Question 18

Who first proposed the idea of antibiotics (and approx when)?

Answer 18

Paul Ehrlich - 1900s

Question 19

Summarise the ideas proposed by Paul Ehrlich

Answer 19

That antibiotics could kill the target pathogen but leave the host unharmed (selective toxicity), and target structures and processes which are unique to humans

Question 20

What was the first dye with antibiotic activity discovered by Ehrlich, and which disease + microbe did it target?

Answer 20

Salvarsan (containing Arsenic) -> targeted Syphilis + Treponema pallidum

Question 21

What was the first antibiotic species to be discovered?

Answer 21

Penicillium (penicillin)

Question 22

What was the first sulphonamide/first commercially available antibiotic?

Answer 22

Prontosil

Question 23

Name (and give examples for) the four main types of antibiotic

Answer 23

1. Cell Wall Synthesis Inhibitors (e.g., penicillin)
2. Protein Synthesis Inhibitors (e.g., aminoglycosides + macrolides)
3. Nucleic Acid Synthesis inhibitors (e.g., quinolones)
4. Folic Acid Biosynthesis (e.g., sulphonamides)

Question 24

Name the two types of effects of antibiotics on bacterial growth

Answer 24

Bacteriostatic (prevents growth) and Bactericidal (kills bacteria)

Question 25

What is the structure found in Cell Wall Synthesis Inhibitor antibiotics, and what molecule does it prevent from being synthesised?

Answer 25

ß-lactam -> inhibits Peptidoglycan biosynthesis

Question 26

What types of bacteria is Penicillin active against?

Answer 26

Gram-positives, e.g., pneumococci, streptococci (does not penetrate Gram-negative outer membrane)

Question 27

How must Penicillin be administered, and why?

Answer 27

Via injection - it is destroyed by gastric pH

Question 28

How does ß-lactam inhibit Peptidoglycan synthesis?

Answer 28

ß-lactam structure mimics D-Ala-D-Ala at end of peptide, so can bind to carboxypeptidase instead of D-Ala-D-Ala

Question 29

How can semi-synthetic Penicillins be made to target Gram-negative bacteria (and name two examples)?

Answer 29

Modification of R1 group by adding hydrophillic NH2 side group allows the antibiotic to pass through outer membrane pores of Gram-negatives (e.g., amoxycilin and ampicillin)

Question 30

What enzyme gives some bacteria penicillin resistance, and what are the two main solutions?

Answer 30

ß-lactamases hydrolyse the ß-lactam ring. 1. Combine with clavulanic acid, a ß-lactamase inhibitor 2. Synthesise ß-lactamase resistant penicillins, e.g., methicillin

Question 31

What are carbapenems and what do they do?

Answer 31

They are ß-lactamase inhibitors, which acylate penicillin binding proteins. They are used to treat penicillin-resistant (i.e. ß-lactamase producing) bacteria

Question 32

How must carbapenems be administered and why?

Answer 32

Intravenously/intramuscularly - they cannot cross the gastrointestinal membrane

Question 33

What are the two main types of carbapenem resistance?

Answer 33

1. Enzymes which hydrolyse the ß-lactam ring (3 classes) 2. Mutations that reduce influx or increase efflux of the drug

Question 34

Which gene allows Methicillin Resistance in MRSA (and how)?

Answer 34

mecA - it encodes penicillin binding protein 2A (which has low affinity for ß-lactam antibiotics and does not bind to them)

Question 35

What does vancomycin do and what is its role as an antibiotic?

Answer 35

It inhibits cell wall synthesis in Gram-positives by binding to D-ALA-D-ALA INSTEAD OF CARBOXYPEPTIDASE; it is used as a drug of last resort to treat MRSA

Question 36

Name the microbe that produces vancomycin

Answer 36

Amycolatopsis orientalis

Question 37

How do some bacteria develop resistance to vancomycin?

Answer 37

Modification of D-Ala-D-Ala target by exchanging terminal D-Ala for L-serine or D-lactate

Question 38

Name the three main types of Protein Synthesis Inhibitor antibiotics; and provide three examples of the first type

Answer 38

Aminoglycosides (e.g., kanamycin, gentamycin, streptomycin), Tetracyclines, Macrolides

Question 39

What do Aminoglycosides do and how must they be administered?

Answer 39

They bind to 30S in aerobic bacteria, preventing 50S from joining; they also create fissures in the outer membrane (enhanced antibiotic uptake). They must be administered intramuscularly/intravenously as they cannot be absorbed through the gut

Question 40

What do tetracyclines do?

Answer 40

They are broad spectrum and they bind to the 30S -> notably, they can penetrate macrophages for intracellular infections

Question 41

What do macrolides do (and name one example)?

Answer 41

Macrolides (e.g., erythromycin) bind to the 50S in Gram-positives, and prevent incoming tRNAs + Amino Acids from binding to nascent polypeptide chain

Question 42

Name the major group of Nucleic Acid Synthesis inhibitors (and one example)

Answer 42

Fluoroquinolones (e.g., ciproflaxin)

Question 43

What do fluoroquinolones (e.g., ciproflaxin) do?

Answer 43

They bind to - and inhibit - DNA gyrase, preventing it from supercoiling DNA. Thus, they inhibit DNA replication

Question 44

What are the two main groups of antimetabolite antibiotics (and what process do they both target)?

Answer 44

Sulphonamides and Trimethoprim (usually used in combination) -> Folic Acid Synthesis!

Question 45

What do sulphonamides do?

Answer 45

They are antimetabolites: competitive inhibitors of dihydropeterate synthase (which is required for Folate Synthesis)

Question 46

What does Trimethoprim do?

Answer 46

Inhibits dihydrofolate reductase (which is required for Folate Synthesis)

Question 47

Name the antibiotic discovered in 2015 (mentioned), what does it essentially do, and what types of bacteria does it target?

Answer 47

Teixobactin: - it inhibits peptidoglycan biosynthesis -in Gram-positives

Question 48

What does Teixobactin do?

Answer 48

It binds to and forms ß-sheets, then fibrilliar oligomers, with Lipid II (a peptidoglycan precursor), thus obstructing peptidoglycan synthesis

Question 49

Name two recently discovered antibiotics besides Teixobactin

Answer 49

Malacidin (similar to Teixobactin) and retinoids (kills MRSA)

Question 50

Name the bacteria that causes serious food poisoning and has poultry as its reservoir (NOT salmonella)

Answer 50

Campylobacter jejuni (gram-negative motile spirillium) -> especially cipR strains

Question 51

Which type of antibiotic was commonly used PROPHYLACTICALLY in chickens for over 20 years?

Answer 51

Fluoroquinolones (e.g., ciprofloxacin)

Question 52

Name the (first?) multi-resistant strain of bacteria that emerged in 1998

Answer 52

Salmonella typhimurium DT104 (resistant to 6 antibiotics)

Question 53

Name the (mentioned) species of penicillin-resistant penumococci

Answer 53

Streptococcus pneumoniae

Question 54

Name the (mentioned) species of multidrug-resistant mycobacteria

Answer 54

Mycobacterium tuberculosis

Question 55

Name the (mentioned) species of methicillin-resistant bacteria that is only sensitive to vancomycin

Answer 55

Staphylococcus aureus

Question 56

Name the commensal that has become resistant to Vancomycin (species and "other" name)

Answer 56

Enterococcus faecalis: vancomycin-resistant enterococci (VRE)

Question 57

What two reasons can a bacterium have INNATE/NATURAL/INTRINSIC resistance? (And one key example)

Answer 57

Lack of target structure; or impermeable to antibiotic (e.g., mycoplasma pneumoniae lack peptidoglycan)

Question 58

What are the three main mechanisms for acquired antibiotic resistance?

Answer 58

1. Enzymatic inactivation of antibiotic 2. Modification of target 3. Efflux of antibiotic

Question 59

Name the three mechanisms for transfer of resistance genes (and which ones are narrow/broad host range)

Answer 59

1. Transduction via bacteriophage (narrow) 2. Transformation via naked DNA (narrow) 3. Conjugation (broad - between different genera)

Question 60

What is the mechanism for resistance to Aminoglycosides (e.g., streptomycin)?

Answer 60

Enzymes inactivate the antibiotic by adding groups (e.g., acetyl, adenyl), reducing transport into cell

Question 61

What is the mechanism for resistance to tetracycline?

Answer 61

Active efflux - cytoplasmic membrane proteins catalyse transport of Tet out of the cell