Antibiotics: Quinolones and Lipopeptides

Question 1

What was the first quinolone, what type of gram does it work on

Answer 1

Nalidixic acid, gram positive and gram negative

Question 2

T/F: Nalidixic acid doesn’t work well systemically

Answer 2

True

Question 3

What is the main target of quinolone antibiotics

Answer 3

DNA gyrase in gram negative bacteria

Question 4

How many subunits does DNA gyrase have, what does each subunit do

Answer 4

2/ Subunit A is responsible for DNA cleavage, Subunit B is an ATPase that provides energy for the reaction

Question 5

T/F: DNA gyrase is essential for the cell because without it positively supercoiled DNA are expanded and DNA fragmentation occurs

Answer 5

True

Question 6

What is the mechanism of action for Quinolones

Answer 6

Forms a tertiary complex between DNA, gyrase, and quinolone that cause DNA gyrase to cut the DNA but does not allow the cut to be resealed

Question 7

T/F: Quinolones are bactericidal antibiotics

Answer 7

True

Question 8

What are mechanisms of bacterial resistance to quinolones

Answer 8

Uptake inhibtion, target modifications, target protection, quinolone inactivation

Question 9

What are the common mechanisms to resistance to quinolones

Answer 9

Mutations in DNA gyrase, usually in the A subunit, (target modification)/ active efflux of the drug from the cell (uptake inhibition)

Question 10

Since 2nd generation fluoroquinolones have limited activity against a number of clinically important gram positive bacteria, what organisms do third generation fluroquinolones work well on, why

Answer 10

Streptococci, Staphylococci and Enterococci, are less likely to be removed through efflux pumps

Question 11

What antibiotics act synergestically with quinolones, what is the MOA, why is do they work synergistically

Answer 11

Novobiocin, interferes with the activity of the B subunit of DNA gyrase, in having resistance to quinolones the B subunit is changed but the Novobiocin overcomes this aiding quinolones

Question 12

What is the MOA of the cationic cyclic lipopeptides Daptomycin, what type of gram bacteria does it work against

Answer 12

disrupt the integrity of the bacterial cell membrane due to its positive charge attracting the negative membrane causing leakage of potassium, gram positive

Question 13

T/F: Just like Beta lactams daptomycin also causes the cell to burst

Answer 13

False: Though there is leakage of potassium the cell doesn’t lyse when interacting with Daptomycin

Question 14

What are mechanism of resistance to daptomycin

Answer 14

D-alynated teichoic acid and D-alanylated lipoteichoic acid, Lysinylated phosphatidyglycerol

Question 15

What are another class of cationic cyclic lipopeptides

Answer 15

Polymyxins

Question 16

What are the two Polymixins, which is the last resort for resistant bacteria

Answer 16

Polymixin B and Polymyxin E (colistin)/ Colistin

Question 17

What type of gram bacteria do polymixins work against

Answer 17

Gram negative bacteria

Question 18

What is the key difference between polymxins and Daptomycin

Answer 18

Cell lysis when inserted into the membrane to assemble channels/pores

Question 19

Why are cationic cyclic lipopeptides selective to bacteria

Answer 19

Eukaryotic cell membranes are more neutral due to being zwitterionic phospholipids

Question 20

T/F: Certain resistance mechanisms for either polymyxin or daptomycin also confer resistance to cationic antimicrobial peptides in the innate immune system

Answer 20

True

Question 21

What is a new antibiotic resistance to polmixin that is troublesome

Answer 21

Plasmid (plasmid-mediated colistin resistance)

Question 22

What is a consequence of overuse/misuse of antibiotics

Answer 22

Development of many disorders associated with alteration of gut microbiota

Question 23

T/F: Though oral antibiotics can effect gut microbiota IV antibiotics do not since they do not enter the stomach

Answer 23

False: IV antibiotics can still reach the gut via biliary excretion

Question 24

T/F: No matter what the antibiotic is working against it will bacterocidal always or bacteriostatic always

Answer 24

False: Antibiotiocs can switch between bacteriostatic or bacteriocidal depending on the organism

Question 25

What is collective antibiotic resistance

Answer 25

If two strands are present and one is susceptible while the other is resistant, the resistant strain can cause change in the antibioitc allowing the susceptible strains to grow over time

Question 26

What is a resistance to Beta-lactam and vancomycin antibiotics that has lead to alternate gene expression

Answer 26

Senor proteins detect the antibiotcs leading to activation of transcription factors that aid in expressing resistance genes

Question 27

How can IV antibiotics lead to gut microbiota resistance

Answer 27

The antibiotics become sub-MIC leading to sensor proteins activating with no actual antibiotic effect occuring

Question 28

T/F: A higher MIC leads to more resistance

Answer 28

True

Question 29

T/F: Exposure to antibiotics at birth or during pregnancy leads to a worse defense against bacterial infection and increases risk chronic disease

Answer 29

True

Question 30

What antibioitics increase the risk of getting hospital-cquired Clostridium difficile infection, why

Answer 30

Cephalosporins, Clindamycin, Fluroquinolones/ loss of gut bacterial diversity and causes antibiotic resistance

Question 31

T/F: In order for quinolones to target gram positive organisms they instead target Topoisomerase IV

Answer 31

True