Antibiotics: Quinolones and Lipopeptides Flashcards
What was the first quinolone, what type of gram does it work on
Nalidixic acid, gram positive and gram negative
T/F: Nalidixic acid doesn’t work well systemically
True
What is the main target of quinolone antibiotics
DNA gyrase in gram negative bacteria
How many subunits does DNA gyrase have, what does each subunit do
2/ Subunit A is responsible for DNA cleavage, Subunit B is an ATPase that provides energy for the reaction
T/F: DNA gyrase is essential for the cell because without it positively supercoiled DNA are expanded and DNA fragmentation occurs
True
What is the mechanism of action for Quinolones
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
T/F: Quinolones are bactericidal antibiotics
True
What are mechanisms of bacterial resistance to quinolones
Uptake inhibtion, target modifications, target protection, quinolone inactivation
What are the common mechanisms to resistance to quinolones
Mutations in DNA gyrase, usually in the A subunit, (target modification)/ active efflux of the drug from the cell (uptake inhibition)
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
Streptococci, Staphylococci and Enterococci, are less likely to be removed through efflux pumps
What antibiotics act synergestically with quinolones, what is the MOA, why is do they work synergistically
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
What is the MOA of the cationic cyclic lipopeptides Daptomycin, what type of gram bacteria does it work against
disrupt the integrity of the bacterial cell membrane due to its positive charge attracting the negative membrane causing leakage of potassium, gram positive
T/F: Just like Beta lactams daptomycin also causes the cell to burst
False: Though there is leakage of potassium the cell doesn’t lyse when interacting with Daptomycin
What are mechanism of resistance to daptomycin
D-alynated teichoic acid and D-alanylated lipoteichoic acid, Lysinylated phosphatidyglycerol
What are another class of cationic cyclic lipopeptides
Polymyxins
What are the two Polymixins, which is the last resort for resistant bacteria
Polymixin B and Polymyxin E (colistin)/ Colistin
What type of gram bacteria do polymixins work against
Gram negative bacteria
What is the key difference between polymxins and Daptomycin
Cell lysis when inserted into the membrane to assemble channels/pores
Why are cationic cyclic lipopeptides selective to bacteria
Eukaryotic cell membranes are more neutral due to being zwitterionic phospholipids
T/F: Certain resistance mechanisms for either polymyxin or daptomycin also confer resistance to cationic antimicrobial peptides in the innate immune system
True
What is a new antibiotic resistance to polmixin that is troublesome
Plasmid (plasmid-mediated colistin resistance)
What is a consequence of overuse/misuse of antibiotics
Development of many disorders associated with alteration of gut microbiota
T/F: Though oral antibiotics can effect gut microbiota IV antibiotics do not since they do not enter the stomach
False: IV antibiotics can still reach the gut via biliary excretion
T/F: No matter what the antibiotic is working against it will bacterocidal always or bacteriostatic always
False: Antibiotiocs can switch between bacteriostatic or bacteriocidal depending on the organism
