LM 2.32: Antibiotic Resistance I

Question 1

what are the 4 things contributing to antibiotic resistance?

Answer 1

1. antibiotic pipeline
2. antibiotic overuse
3. inadequate infection control
4. resistance

Question 2

what is the antibiotic pipeline?

Answer 2

the supply of new antibiotics

there was a 40 year gap where no antibiotics were even being made

Question 3

what does resistance mean?

Answer 3

the bacteria are not inhibited by clinically-achievable, nontoxic levels of the antibiotic

sometimes bacteria can be killed by an antibiotic, but if the level of antibiotic would kill the patient then the bacteria are considered resistant

Question 4

what is the Kirby-Baur method?

Answer 4

spread bacteria on agar plate

then put a drug in the middle of the agar

bacteria will only grow far away from the disc if the bacteria is responsive to bacteria

zone of inhibition!!

Question 5

why didn’t we see antibiotic resistance coming?

Answer 5

it’s rare and sometimes it even weakens the bacteria…

so the chance that a given mutation will give antibiotic resistance but not kill the human cell and not cause harm to the bacteria is rare…

also bacteria grow clonally so normal growth does not spread beneficial mutations –> there’s no sexual recombination, no reassortment and offspring are genetically identical; so if you get resistance in one lineage, they can’t help other lineages (or so we thought)

unfortunately it turns out that bacteria have a way to exchange genes

Question 6

what are the 3 basic machnisms by which resistance and other genes can spread between bacteria?

Answer 6

1. conjugation
2. transduction
3. transformation

**bacteria CAN exchange genes!!

Question 7

what is transformation?

Answer 7

the cells lyse/pump out and release DNA

DNA is taken up into a new bacteria cell – not all cells are capable of doing this though (only naturally competent cells can do this)

ex. strep. pneumoniae

then the new DNA is integrated and can lead to antibiotic resistance

Question 8

what is transduction?

Answer 8

DNA is carried inside a virus that infect bacteria = bacteriophage

bacteriophages just carry viral DNA back and forth

they inject their DNA into the bacteria and then take over the cell to get it to produce viral components –> during assembly process the viral precursors package bacteriophage DNA

then the bacteriophage that are released when the cell burst are released go on to kill other bacteria and are carrying nothing but viral DNA

however, in the case of transducing phages, at a low rate the virus packages bacterial DNA

then when these phages are released, they’re releasing bacterial DNA!

Question 9

what is conjugation?

Answer 9

there is direct transfer between two physically adjacent cells leading to DNA transfer that can result in antibiotic resistance

they use pili to bring other bacteria cells next to each other

conjugation involves plasmid = smaller version of the chromosome that has optional genes on it that give you extra super powers like adhesins and exotoxins or antibiotic-resistance proteins

some plasmids code for the ability to transfer from cell to cell!

Question 10

what are replicons?

Answer 10

they can replicate as independent DNA molecules from their own origins

plasmids and chromosomes are both replicons

to replicate you need an ori sequence

conjugative plasmids have an ori sequence and also a second origin called oriT used only during conjugation

conjugative plasmis can also integrate into chromosomes

Question 11

what is Hfr?

Answer 11

high frequency gene transfer

if a conjugative plasmid integrates into a chromosome you start getting replication from oriT and transfer, the transfer replicase just keeps going because it looks like one big DNA molecules

this way you can get the entire chromosome transfered from one chromosome to another and this can give you recombination

so the importance of Hfr is you can use conjugation to transfer the whole chromosome between bacteria cells

Question 12

what is mutational resistance?

Answer 12

resistance that arises via a newly occurring mutation

TB relies on this

Question 13

what is importing resistance?

Answer 13

importing new resistance genes via transduction, transformation, conjugation

this is a really efficient way to spread antibiotic resistance

most bacteria rely on this

Question 14

what is intrinsic resistance?

Answer 14

arises from antibiotic produces have to have ways to avoid suicide

if you’re making an antibiotic you have to have ways to avoid suicide

so fungi are intrinsically resistant to B-lactams like penicillin

can’t transfer to other bacteria…

Question 15

what is active resistance?

Answer 15

when you make something that protects you like an enzyme

ex. strep fradiae pumps out neomycin and it produces an enzyme that inactivates any neomycin that comes back into the cell

active resistance is transferable to other bacteria! transformation, transduction, conjugation

Question 16

what are the 5 basic mechanisms of which bacteria resist antibiotics?

Answer 16

1. blocking entry or accumulation of the drug
2. blocking binding by altering target (so let the antibiotic in but block the target, like the ribosome for example)
3. producing a replacement of the target that is resistant to the antibiotic (rare)
4. hydrolyzing or modifying the antibiotic (ex. B-lactamase)
5. failing to activate the antibiotic (only 1: isoniazid)

Question 17

how easy is it for bacteria to exchange genes?

Answer 17

the more different two bacterial species are the more limitations there are on their ability to exchange genes

soil microbes are very different from clinically relevant microbes

also with transduction, the phage adhesin and recipient have to match

this is one of the reasons that spread to distantly-related species was unexpected