Module 7 - Epidemiology, Antibiotics and Antibiotic Resistance Flashcards
Distinguish between Endemic, Epidemic and Pandemic disease
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
Name the disease that is responsible for the amphibian decline, and what kind of outbreak/disease is this?
Chytridiomycosis (panzootic -> animal pandemic)
Name 6 pandemic plant diseases
Maize Lethal Necrosis
Rice tungro
Sweet potato virus
Banana bunchy top
Citrus Tristeza Virus
Plum Pox
Name the two parameters for measuring disease rate (and define these)
Morbidity rate -> number of individuals becoming ill
Mortality rate -> rate of death from disease
What number is sometimes used as the threshold to define epidemics?
400 cases per 100,000 population per week
What are the two types of epidemics? (And define them)
Common source epidemic -> sharp rise to a peak and rapid decline (e.g., food poisoning)
Propagated epidemic -> slow rise and gradual decline
Approximately what percentage of population immunity is required to prevent the spread of measles, flu and polio respectively?
Measles: 90-95%
Flu: 90%
Polio: 70%
What is the approximate susceptible population size required to sustain measles in a community?
250,000 - 300,000
What are the two main sources of change in organisms that can render immunity ineffective?
Antigenic drift and antigenic SHIFT
Define antigenic drift
Minor antigenic variation -> Haemagglutanin or Neuraminidase can change due to genetic mutations altering amino acid sequences
Define Antigenic Shift
More significant antigenic variation -> reassortment of segments of genome due to gene exchange between strains
What four main things do epidemiologists investigate to understand disease?
The pathogen
The source of the pathogen
Reservoirs and Carriers
Transmission of Pathogens (e.g., airborne/contact/vector)
What are the three main types of disease control measure?
Eliminate source
Break connection between source and host
Raise level of herd immunity (vaccinate)
What genus of virus causes Zika (also genome type)
Flavivirus (ssRNA)
How is Zika virus transmitted?
Mosquito, Sexually, Blood Transfusion, in utero
What are some of the main factors responsible for emergence of new pathogens and re-emergence of known pathogens?
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
Name the organism that causes the Black Death
Yersinia pestis
Who first proposed the idea of antibiotics (and approx when)?
Paul Ehrlich - 1900s
Summarise the ideas proposed by Paul Ehrlich
That antibiotics could kill the target pathogen but leave the host unharmed (selective toxicity), and target structures and processes which are unique to humans
What was the first dye with antibiotic activity discovered by Ehrlich, and which disease + microbe did it target?
Salvarsan (containing Arsenic) -> targeted Syphilis + Treponema pallidum
What was the first antibiotic species to be discovered?
Penicillium (penicillin)
What was the first sulphonamide/first commercially available antibiotic?
Prontosil
Name (and give examples for) the four main types of antibiotic
- Cell Wall Synthesis Inhibitors (e.g., penicillin)
- Protein Synthesis Inhibitors (e.g., aminoglycosides + macrolides)
- Nucleic Acid Synthesis inhibitors (e.g., quinolones)
- Folic Acid Biosynthesis (e.g., sulphonamides)
Name the two types of effects of antibiotics on bacterial growth
Bacteriostatic (prevents growth) and Bactericidal (kills bacteria)
What is the structure found in Cell Wall Synthesis Inhibitor antibiotics, and what molecule does it prevent from being synthesised?
ß-lactam -> inhibits Peptidoglycan biosynthesis
What types of bacteria is Penicillin active against?
Gram-positives, e.g., pneumococci, streptococci (does not penetrate Gram-negative outer membrane)
How must Penicillin be administered, and why?
Via injection - it is destroyed by gastric pH
How does ß-lactam inhibit Peptidoglycan synthesis?
ß-lactam structure mimics D-Ala-D-Ala at end of peptide, so can bind to carboxypeptidase instead of D-Ala-D-Ala
How can semi-synthetic Penicillins be made to target Gram-negative bacteria (and name two examples)?
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)
What enzyme gives some bacteria penicillin resistance, and what are the two main solutions?
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
What are carbapenems and what do they do?
They are ß-lactamase inhibitors, which acylate penicillin binding proteins. They are used to treat penicillin-resistant (i.e. ß-lactamase producing) bacteria
How must carbapenems be administered and why?
Intravenously/intramuscularly - they cannot cross the gastrointestinal membrane
What are the two main types of carbapenem resistance?
- Enzymes which hydrolyse the ß-lactam ring (3 classes)
- Mutations that reduce influx or increase efflux of the drug
Which gene allows Methicillin Resistance in MRSA (and how)?
mecA - it encodes penicillin binding protein 2A (which has low affinity for ß-lactam antibiotics and does not bind to them)
What does vancomycin do and what is its role as an antibiotic?
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
Name the microbe that produces vancomycin
Amycolatopsis orientalis
How do some bacteria develop resistance to vancomycin?
Modification of D-Ala-D-Ala target by exchanging terminal D-Ala for L-serine or D-lactate
Name the three main types of Protein Synthesis Inhibitor antibiotics; and provide three examples of the first type
Aminoglycosides (e.g., kanamycin, gentamycin, streptomycin), Tetracyclines, Macrolides
What do Aminoglycosides do and how must they be administered?
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
What do tetracyclines do?
They are broad spectrum and they bind to the 30S -> notably, they can penetrate macrophages for intracellular infections
What do macrolides do (and name one example)?
Macrolides (e.g., erythromycin) bind to the 50S in Gram-positives, and prevent incoming tRNAs + Amino Acids from binding to nascent polypeptide chain
Name the major group of Nucleic Acid Synthesis inhibitors (and one example)
Fluoroquinolones (e.g., ciproflaxin)
What do fluoroquinolones (e.g., ciproflaxin) do?
They bind to - and inhibit - DNA gyrase, preventing it from supercoiling DNA. Thus, they inhibit DNA replication
What are the two main groups of antimetabolite antibiotics (and what process do they both target)?
Sulphonamides and Trimethoprim (usually used in combination) -> Folic Acid Synthesis!
What do sulphonamides do?
They are antimetabolites: competitive inhibitors of dihydropeterate synthase (which is required for Folate Synthesis)
What does Trimethoprim do?
Inhibits dihydrofolate reductase (which is required for Folate Synthesis)
Name the antibiotic discovered in 2015 (mentioned), what does it essentially do, and what types of bacteria does it target?
Teixobactin:
- it inhibits peptidoglycan biosynthesis
-in Gram-positives
What does Teixobactin do?
It binds to and forms ß-sheets, then fibrilliar oligomers, with Lipid II (a peptidoglycan precursor), thus obstructing peptidoglycan synthesis
Name two recently discovered antibiotics besides Teixobactin
Malacidin (similar to Teixobactin) and retinoids (kills MRSA)
Name the bacteria that causes serious food poisoning and has poultry as its reservoir (NOT salmonella)
Campylobacter jejuni (gram-negative motile spirillium) -> especially cipR strains
Which type of antibiotic was commonly used PROPHYLACTICALLY in chickens for over 20 years?
Fluoroquinolones (e.g., ciprofloxacin)
Name the (first?) multi-resistant strain of bacteria that emerged in 1998
Salmonella typhimurium DT104 (resistant to 6 antibiotics)
Name the (mentioned) species of penicillin-resistant penumococci
Streptococcus pneumoniae
Name the (mentioned) species of multidrug-resistant mycobacteria
Mycobacterium tuberculosis
Name the (mentioned) species of methicillin-resistant bacteria that is only sensitive to vancomycin
Staphylococcus aureus
Name the commensal that has become resistant to Vancomycin (species and “other” name)
Enterococcus faecalis: vancomycin-resistant enterococci (VRE)
What two reasons can a bacterium have INNATE/NATURAL/INTRINSIC resistance? (And one key example)
Lack of target structure; or impermeable to antibiotic (e.g., mycoplasma pneumoniae lack peptidoglycan)
What are the three main mechanisms for acquired antibiotic resistance?
- Enzymatic inactivation of antibiotic
- Modification of target
- Efflux of antibiotic
Name the three mechanisms for transfer of resistance genes (and which ones are narrow/broad host range)
- Transduction via bacteriophage (narrow)
- Transformation via naked DNA (narrow)
- Conjugation (broad - between different genera)
What is the mechanism for resistance to Aminoglycosides (e.g., streptomycin)?
Enzymes inactivate the antibiotic by adding groups (e.g., acetyl, adenyl), reducing transport into cell
What is the mechanism for resistance to tetracycline?
Active efflux - cytoplasmic membrane proteins catalyse transport of Tet out of the cell
