UNIT 3 DAY 2 - EVOLUTION OF RESISTANCE TO ANTIBIOTICS

Question 1

coevolution of host and pathogen analogy

Answer 1

humans arms race

Question 2

why is a humans arms race an analogy for the coevolution of host and parasite/pathogen

Answer 2

• host and parasites must both evolve as fast as they can to maintain their current levels of adaptation

Question 3

humans resistance to pathogens

Answer 3

• pathogens can evolve faster than human resistance because cells produce faster

Question 4

antibiotic resistance abilities

Answer 4

• 95% of staph, previously controlled by penicillin is penicillin resistant (80 years)
• 75% of gonorrhoea strains make enzymes that inactivate once effective bacteria
• salmonella resistance to antibiotics caused by genetic changes from long-term antibiotic use
• amoxicillin is no longer effective against 30-50% of pathogenic E. coli
• 1/3 tuberculosis cases resistant (30% chance of survival without antibiotics)

Question 5

N&W first conclusion about the evolution of antibiotic resistance to antibiotics

Answer 5

• bacterial resistance to antibiotics arises not by the gradual development of tolerance by individual bacteria but by rare gene mutations or new genes introduced by plasmids
• populations are the ones that evolve not individuals because individuals retain the same genes throughout their lives

Question 6

N&W second conclusion about the evolution of antibiotic resistance to antibiotics

Answer 6

• gene mutations can be transmitted by plasmid infection or other processes to different species of bacteria
• between species transmission of resistance factors by plasmids is a problem because they provide genetic variation helping the spread of antibiotic resistant genes

Question 7

N&W third conclusion about the evolution of antibiotic resistance to antibiotics

Answer 7

• presence of an antibiotic causes the initially rare mutant strain to increase and gradually replace the ancestral type
• this is consistent with how natural selection is expected to change population overtime

Question 8

N&W fourth conclusion about the evolution of antibiotic resistance to antibiotics

Answer 8

• if the antibiotic is removed, ancestral strains slowly replace the resistant forms
• the biological explanation for why this happens is: the disadvantage of resistant gradually lost by further evolutionary changes

Question 9

N&W fifth conclusion about the evolution of antibiotic resistance to antibiotics

Answer 9

• mutations within a resistant strain can confer still greater resistance, so that increasing the dose of an antibiotic may be effective only temporarily
• an antibiotic is a temporary fix until the bacteria becomes resistant to it and then is able to become resistant to others because of the antibiotic similar makeups

Question 10

N&W seventh conclusion about the evolution of antibiotic resistance to antibiotics

Answer 10

• mutations that confer still higher levels of resistance arise in such partially adapted strains more often than in the original nonresistant strain

Question 11

N&W eighth conclusion about the evolution of antibiotic resistance to antibiotics

Answer 11

• resistance to one antibiotic may confer resistance to another
• an antibiotic is a temporary fix until the bacteria becomes resistant to it and then is able to become resistant to others because of the antibiotic similar makeups

Question 12

N&W ninth conclusion about the evolution of antibiotic resistance to antibiotics

Answer 12

• disadvantage of resistant strains in the absense of an antibiotic is gradually lost by furtjer evolutionary changed, so that resistance can prevail even where no antibiotics have been used for a long time
• cost to resistance strain is eventually lost by further evolutionary changes
• 1st mutation = resistant gene
• 2nd mutation = a change that reduces the cost of resistance

Question 13

evolutionary theory hypothesis

Answer 13

the gene flow of antibiotic resistant genes

Question 14

plasmids

Answer 14

• extrachromosomal DNA molecule –> replicates independently of the chromosomal DNA
• much smaller, just a few to 200,000 base pairs, existing in multiple copies within a bacterium
• can replicate with 1 bacterium and transfer copies of themselves to 2nd bacterium by conjugation

Question 15

Lenski - How do mutations for resistance function?

Answer 15

• disrupting some normal physiology process in the cell, thereby causing detrimental side-effects

Question 16

Lenski - mutations for resistance confer an advantage when antibiotic are present but also:

Answer 16

• environment containing antibiotics, possession of a corresponding resistance gene beneficial to bacteria
• absence of antibiotics, resistant genotypes may have lower growth rate than sensitive counterparts
• mutations for resistance have disadvantages without mutations because they disrupt normal processes within the cell, hindering success in the environment
• resistant bacteria –> inferior competitors to sensitive genotypes in absence of antibiotics
• less tradeoffs that resistance has, longer time needed to eradicate mutant bacteria

Question 17

Lenski - results and discussion

Answer 17

• many studies show that mutant bacteria are less fit
• carriage of plasmids and expressions of plasmid encodes resistance functions
• caveat studies performed in “naive bacteria” not adopted to resistance funtiosn

Question 18

Schrag and Perrot

Answer 18

• streptomycin resistance gene (rpsL) gene in E. coli mutated –> changed shape of ribosome to allow it assenille proteins even when. antibiotic
• initial cost of resistance, competitive handicaps substantially reduced 200 generations later
• gene mutations outside of rpsL caused decreased cost of resistance

Question 19

Ribosomes

Answer 19

• constructed of proteins and r-RNA, site of protein synthesis in all cells
• an mRNA, translated from DNA, transcribed into a protein when a series of tRNA

Question 20

Schrag and Perrot Ribsomes role

Answer 20

• antibiotic streptomycin kills bacteria by blocking protein assembly on the ribosomes
• a mutation in one of the genes that builds ribosomes (rpsL gene) changes the shape of the ribosome such that it can continue to function even in the presence of the antibiotic
• mutant ribosomes, however, string together amino acids more slowly than non-mutant ribosomes, which slows the growth rate of the bacteria that contain them

Question 21

Schrag and Perrot insecticide dicizinan

Answer 21

• flies developed resistance and with removal of insecticide were hampered initially, eventually evolved to be just as strong in absence of insecticide

Question 22

Schrag and Perrot

Answer 22

1. sensitivity of bacteria pathogens to antibiotics = natural resouce and beneficial to humans BUT has been depleted and there is major resistance
2. antibiotic sensitivity = renewable resource; if there is a cost, top use of antibiotics, resistant strain would die off
3. after evolving resistance, bacteria may adapt to cost –> hard to “renew’ sensitivity

Question 23

Taubes (2008)

Answer 23

• MRSA (methicillin-resistant staphypoccous alleles) especially worrisome due to resistance to marry antibiotics and threat to life
• many pathogen bacteria come from good bacteria growing in the wrong place
• how hospital pathogens acquire resistance exchanging DNA with other bacteria through plasmids, or gene cassettes

Question 24

Taubes (2008)

Answer 24

• penicillin-like antibiotics work by attacking cell wall enzymes in bacteria
• penicillinase enzyme from resistant bacteria –> decomposes ring-like structure of penicillin
• resistance to methicillin gene (meCA) produces surrogate binding protein to keep antibodies at bay

Question 25

Taubes (2008)

Answer 25

• MRSA has history of outbreaks in hospitals but also seen in other areas
• VRSA less of a threat die to competition disadvantage in broader environment (plasmid mutation)

Question 26

gram-positive bacteria

Answer 26

• bacteria that have simple cell walls with peptidoglycan (single cell membrane) (MRSA)

Question 27

Gram-negative bacteria

Answer 27

• have structurally more complex cell walls, thinner peptidoglycan later and an outer membrane that contains molecules called lipopolysaccharides

Question 28

MRSA

Answer 28

strain of staphylococcus aureus resistant to methicillin