Antibiotic Resistance

Question 1

What is antimicrobial resistance?

Answer 1

when bacteria, fungi, viruses etc are no longer responsive to antimicrobial medicines — they become ineffective and infections become difficult or impossible o treat

Question 2

Biological Resistance

Answer 2

changes that result in reduced susceptibility of an organism to a set agent
- ongoing process

Question 3

Clinical Resistance

Answer 3

when the drug is no longer effective for clinical use against a set organism=== organism has clinical resistance

Question 4

3 aspects of antimicrobial R

Answer 4

Drug
Microorganism
Environment

Question 5

What is environmentally mediated antimicrobial R

Answer 5

R directly resulting from chemical/physical traits of the enviroment that either directly change drug or alter the microorganism’s normal response to the drug

Ex// pH - gentamicin needs low Ph to be effective/MIC

Question 6

Ex// Aminoglycosides and Divalent cations

Answer 6

divalent cations form environment bind to the negatively charged binding sites on outer membrane of Pseudomonas aeruginosa ; block aminoglycosides from getting to target + working

Question 7

What is microorganism mediated antimicrobial R

Answer 7

R that results from genetically encoded traits of micro
- can be intrinsic or acquired

Question 8

Intrinsic R

Answer 8

naturally resistant to a certain antibiotic/family of them without need for mutation or gain of further genes

ex// aerobic bacteria not able to anaerobically reduce certain antibiotic to active form ; penicillin and gram -

Question 9

Acquired R

Answer 9

get R through a new genetic mutation or by getting DNA from resistant bacteria

Question 10

How are resistance genes normally transferred bw bacteria

Answer 10

plasmids or transposons (mobile genetic elements)
- can transfer horizontally bw bacteria

Question 11

Bacterial conjugation

Answer 11

bw F+ and F- bacteria
- F+ bacteria has sex pilus; pulls F- bacteria in close to it
- form mating bridge: don’t physically touch but PM gets more permeable and allow for bidirectional gene transfer

Question 12

Transduction by bacteriophage

Answer 12

• bacteriophage inserts its DNA into donor bacteria cell —- production of phage DNA and proteins to start form packages
• sometimes donor DNA gets broken and incorporate into phage capsid
• cell with phage shit lyses and releases more phage that now have bacteria DNA incorporated in it
• infect new cell - insert DNA with bacteria DNA into new bacteria (recombination can occur)

can happen with chromosome or extrachromosomal DNA

Question 13

What are the 4 mechanisms of R

Answer 13

1) modification (chemical) or destruction of antimicrobial molecule
2) prevention of antibiotic reaching target
3) changes and or bypass target site
4) R due to global cell adaptive processes

Question 14

Transformation of Bacteria

Answer 14

Recipient takes up donor DNA that is complementary to recipient DNA
- donor DNA aligns with recipient complementary base pairs
- recombination occurs bw the two — donor DNA incorporated into genome

Question 15

Modification of antimicrobial: Chemical conjugation

Answer 15

3 types of modifications: acetylation, phosphorylation or adenylation

causes steric hinderance - can’t get to target and have effects

• generally impacts antibiotics that inhibit protein synthesis at ribosome

Ex// aminoglycoside modifying enzyme (AME)

Question 16

Ex// Destruction of Antibiotic : beta lactamases

Answer 16

• open up B lactam ring and alter it so that it can’t bing to penicillin-binding proteins (PBPs)

— antibiotic isn’t able to stop cell wall synthesis anymore

Question 17

Ways to decrease penetration of antibiotic

Answer 17

decrease permeability of cell
- efflux pumps

Question 18

T or F: a lot of antibiotics have intracellular targets

Answer 18

T

Question 19

How do we decrease permeability of bacteria cells

Answer 19

change in porins: types, expression or impair their function

Ex// in gram - bacteria: changes to the number of traits of outer membrane porins contributes to B-lactam R

Question 20

Types of Efflux pumps

Answer 20

1) Small multidrug resistance family
2) Major Facilitator Superfamily (MFS)
3) The ATP binding cassette family (ABC)
4) Multidrug and toxic compound extrusion family (MATE)
5) Resistance modulation cell division family (RND)

Question 21

Ways to change target site

Answer 21

1) Target protection: Tet(M) dislodges tetracycline that was bound to ribosome

2) Modify target site: mutations of the target site or enzyme alteration of the target site

3) Complete replacement or bypass of target site:

Question 22

What is changes in global cell adaptive processes

Answer 22

not just one mutation driving process — group of genes help

various gene clusters work together to make less antibiotics less effective

Question 23

Pathways for Beta lactam R

Answer 23

1) Enzyme destruction
2) Decreased uptake to B-lactam
3) Altered target

Question 24

MoA of glycopeptide antibiotics

Answer 24

biden to AA in cell wall to prevent addition of new units to the peptidoglycan

Question 25

Resistance to Glycopeptides

Answer 25

change target site: alter cell wall precursors so that they don’t bind to vancomycin /no inhibition of peptidoglycan

** commonly have high amount of R seen in enterococci

Question 26

R to Aminoglycosides

Answer 26

1) Enzyme modification: modify the drug directly (changes its affinity for the 30S unit; can’t bind)

2) Altered target: mutational changes in ribosomal binding site

3) Decreased uptake: change number and trait of porins

Question 27

T or F: R bacteria can pass from animals to humans

Answer 27

T; can also spread to environment —- go to humans via environment

Question 28

Why is resistance rising

Answer 28

misuse of antibiotics: use for common cold, use in animal feed, using leftover rx