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MICR 341 - Quiz 4 > quiz 5 > Flashcards

quiz 5 Flashcards

1
Q

what is considered a GOOD antibiotic?

A
  1. no side effects
  2. far more toxic for bacteria than mammalian cells
  3. broad spectrum of activity to facilitate rapid medical intervention
  4. appropriate bioavailability, must reach site of infection
  5. low cost to develop and manufacture
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2
Q

what is the disadvantage of broad spectrum antibiotics?

A

affects the normal microbiota

e.g., C. Difficile infection and vaginal tract infection

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3
Q

tolerance of the patient for the antibiotic is affected by a wide variety of …

A

genetic factors (age, pregnancy, etc)

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4
Q

why are older antibiotics being brought back for usage?

A

Because of antibiotic resistance. They initially were stopped because of serious side effects, but are now used as a last resort due to antibiotic resistance

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5
Q

antibiotics and ____ affect the normal microbiota

A

antiseptics

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6
Q

what are the reasons for antibiotics potentially being the cause of developing certain diseases/conditions?

A

if they are taken with several other antibiotics before the age of five

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7
Q

antibiotic resistance genes come from and/or have evolved from the ______

A

environmental resistome

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8
Q

what consists of the environmental resistome?

A
  1. cryptic embedded genes
  2. pathogens
  3. antibiotic producers
  4. precursor genes
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9
Q

what are the 4 main mechanisms of antibiotic resistance?

A
  1. restriction of the access of the antibiotic to its target
  2. inactivation or modification of the antibiotic
  3. modification of the antibiotic target
  4. inactivation of a pathway critical for activation of the antibiotic, such as Metronidazole
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10
Q

what do multi-drug resistant bacteria possess?

A

many different mechanisms to resist many different antibiotics

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11
Q

what are antibiotic resistant genes acquired by?

A

horizontal gene transfer (HGT) and point mutations

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12
Q

What are the general bacterial factors that limit access of the antibiotic to its target?

A
  1. outer membrane porins
  2. transporters
  3. efflux pumps
  4. enzyme inactivation and modification
  5. modification of the target
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13
Q

what is the function of outer membrane porins?

A

allow selective diffusion of small molecules across the outer membrane of Gram-negative bacterial cells, including nutrients, ions and antibiotics

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14
Q

large antibiotics such as ____, are too bulky to diffuse through ____

A

vancomycin

outer membrane porins

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15
Q

what do point mutations in outer membrane porins result in?

A

restrict access to the periplasm, cytoplasmic membrane, and to the cytoplasm

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16
Q

what do point mutations in bacterial transporters result in?

A

alteration of antibiotic susceptibility

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17
Q

due to point mutations in transporters, how does down-regulation of transporters affect E. Coli?

A

becomes 10x more resistant to aminoglycoside (antibiotic) in anaerobic conditions. in anaerobic conditions, down-regulation of a specific transporter occurs to a greater extent than in aerobic conditions.

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18
Q

what is the function of efflux pumps?

A

used by bacteria to pump small molecules out of the cytoplasm and sometimes across the outer membrane. are used to reduce the intracellular concentration of the antibiotic to a level where the antibiotic is ineffective. a VERY EFFICIENT MECHANISM

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19
Q

what is the effect of enzyme inactivation in regards to Beta-Lactams?

A

enzyme inactivation, specifically of beta-lactamase, unaffects Beta-lactam which allows bacteria to be killed

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20
Q

what is the significance of beta-lactamase?

A

evolutionary related to transpeptidases. Activated beta-Lactamase inactivates beta-lactam, which prevents membrane degradation and bacterial cell death.

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21
Q

what is the significance of transpeptidase

A

target of beta-lactam, located in the peptidoglycan layer

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22
Q

what is the significance of Clavulinic acid?

A

inactivates beta-lactamase which keeps beta-lactam active and able to kill bacteria

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23
Q

what is an example of enzyme modification?

A

modification of aminoglycoside

  • N acetylation
  • O phosphorylation
  • O adenylation
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24
Q

what kind of proteins are transpeptidases?

A

penicillin-binding proteins

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25
Q

what do point mutations in penicillin-binding proteins result in?

A

reduce their susceptibility to beta-lactams, rendering the antibiotic ineffective

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26
Q

what is the significance of the mecA gene of S. aureus?

A

encodes a penicillin-binding protein that replaces the normal Beta-lactam sensitive transpeptidase, allowing transpeptidation of the peptidoglycan in the presence of Beta-lactams

27
Q

What is the role of the antibiotic, vancomycin?

A

binds to D-ala-D-ala, preventing cross-linking which causes membrane degradation of the bacteria- kills bacteria

28
Q

what enzymes do vancomycin-resistant bacteria have to prevent the binding of vancomycin to their membrane?

A

VanH, VanA/B, VanX

29
Q

what is the function of enzyme, VanH?

A

catalyzes conversion of pyruvate to D-lactate

30
Q

what is the function of enzyme, VanA/B?

A

leads to the formation of D-ala-D-lactate, vancomycin cannot bind to D-ala-D-lactate

31
Q

what is the function of enzyme, VanX?

A

cleaves D-ala-D-ala that is found by usual pathway, no incorporation into cell wall peptides

32
Q

What is ribosome protection?

A

modification of ribosomal subunits in bacteria, to prevent the binding of antibiotics such as tetracycline

33
Q

streptomycin resistance is mediated by ….

A

amino acid changes in a ribosomal protein, due to point mutations

34
Q

mutation in the ___ -subunit leads to resistance against Rifapin (point mutation)

A

RNAP Beta-subunit

35
Q

what are the two main mechanisms for tetracycline-resistant bacteria?

A

efflux pumps and protected ribosomes

36
Q

what is antibiotic tolerance?

A

when the antibiotic doesn’t block the function of the bacterial cells. unlike resistance, tolerance is not due to mutations or acquisition of resistance genes and is reversible

37
Q

the antibiotics that inhibit cell wall synthesis are ____

A

bactericidal

38
Q

what are bactericidal antibiotics

A

antibiotics that degrade the cell wall during replication, exposing bacteria to osmotic shock

39
Q

why are non replicating bacteria tolerant to bactericidal antibiotics?

A

they do not replicate and therefore do not possess the degradative enzymes so their cell wall is unaffected by the presence of the antibiotic

40
Q

what are persisters?

A

non-growing cells in a bacterial population and are resistant to several antibiotics. form only a small fraction (less than 1%) of the total bacterial population

41
Q

what are additional problems of antibiotic resistance?

A
  1. reduction in virulence fitness - actually calls for natural selection, allowing the strongest virulence factors to prevail
  2. compensatory mutation (intergenic or intragenic) and HGT events can “restore fitness”
  3. resistant bacteria are the ones causing disease
  4. removing selective pressure doesn’t eliminate antibiotic resistance, just slows down its dissemination
42
Q

what factors in the 1950s were reason for the large drop of number of cases of infection?

A
  1. increased hygiene
  2. quality of food
  3. sanitation
  4. vaccination
43
Q

what is the definition of a vaccine?

A

nontoxic, greatly attenuated antigens that are injected, ingested, or inhaled to induce a protective immunity, without having to go through the infection/disease process itself. RISKS/BENEFITS ratio is very low, lower than some antibiotics

44
Q

benefits of vaccination?

A
  1. prevent infectious diseases
  2. reduce symptoms
  3. prevent long-term consequence of diseases (e.g. Shingles)
  4. much cheaper than treatment
  5. the only protection against infectious diseases for which no treatments are available.
45
Q

risks of vaccination?

A

mostly side effects: nausea, headache, fever and pain at the injection site (immune system activation)
*Rare side effects: anaphylaxis (allergic reaction), vaccine strain infection

46
Q

what are the types of barriers of vaccine development?

A

financial, legal and political barriers

47
Q

what infections showed the largest drops in number of cases in Canada?

A

Measles, Mumps, Rubella, Diphtheria, Pertussis, Polio

48
Q

What are the types of vaccines?

A
  1. whole, live non-pathogenic organism
  2. whole organism inactivated by heat or chemical treatment
  3. subunit vaccines
  4. conjugate vaccines
  5. adjuvants
49
Q

what whole, live non-pathogenic vaccine is now avoided due to serious side effects?

A

BCG - cowpox vaccine. provided strong and long-lasting immunity

50
Q

what type of vaccine was the old pertussis vaccine?

A

whole organism inactivated by heat or chemical treatment vaccine

51
Q

what kind of vaccine is the DTaP vaccine?

A

subunit vaccines

52
Q

what is a subunit vaccine?

A

a vaccine that consists of one or more purified proteins, sometimes inactivated, which provides immunity against invariant antigens

53
Q

what is the characteristic of DTaP vaccines?

A

provided immunity is weak, and repeated administration is needed to elicit a strong and long-lasting immunity

54
Q

what are conjugate vaccines used for?

A

development of vaccines against capsulated microorganisms - provide capsular antigens which are bound to protein antigens allowing them to be processed and presented on the MHC-2 complex, needed for antibody-mediated immunity.

55
Q

what are adjuvants?

A

components of the vaccine that stimulate, modify, or augment the immune system activity

56
Q

what was the significance of Dogma?

A

an antivaccination movement that believed vaccines were not necessary and had nothing to do with the huge drops in the number of cases for most infectious diseases since the 1950s

57
Q

What was the relevance of time where anti-vaxxers believed vaccines caused autism?

A

believed it was because of Mercury (thimerosal), and then after that was debunked, believed it was due to the aluminum adjuvant

58
Q

what is an example of a negative outcome due to anti-vaccination movements?

A

whooping cough epidemic in 2014, California

59
Q

whooping cough is caused by which bacteria?

A

Bordetella Pertussis

60
Q

what are the 3 phases of whooping cough?

A
  1. Catarrhal - bacteria attach to ciliated respiratory epithelium, causes similar symptoms to a cold
  2. Paroxysmal - periods of severe spasmodic coughing fits
  3. Convalescent - adaptive immune response kicks in
61
Q

what are the virulence factors of Bordetella Pertussis?

A

Adhesion, Invasion, Biofilm formation on epithelium, Cytotoxicity

62
Q

what are current issues with vaccine development?

A
  1. inability to induce protective immunity due to antigenic variation
  2. serious side effects
  3. inability to induce protective immunity, because the wrong side of the adaptive system was induced.
63
Q

what is more research needed for in vaccine development?

A
  • Discover the immune response needed to clear the infection
  • find vaccine targets that are virulence factors with no antigenic variation
  • find good immunogen

MICR 341 - Quiz 4 (2 decks)

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