Antimicrobial Chemotherapy Flashcards

Question

Origin of antibiotic resistance II

Answer 1

**Fortuitous advantageous mutations** Examples: • Mutations of antibiotic target (such as gyrB): direct • Mutation of regulator that increases expression of efflux pumps: indirect **Expropriating genes** • Kidnapping resistance mechanism from antibiotic producing organisms (such as beta- lactamase, ermC) • Subverting enzymes to perform resistance tasks • Plasmids encoding one or many resistance genes are important in spreading resistance

Answer 2

**Vertical Gene Transfer** Resistance trait passed on from one generation to another, with **clonal expansion**. Resistance trait can be a **mutated gene, or resistance genes can be encoded on chromosome or plasmids** **Horizontal Gene Transfer** Resistance trait transferred to a different bacteria Transfer occurs mostly by **conjugation of plasmids**, but can also occur by **transformation in naturally competent bacteria**

Answer 3

-Impaired受损的 influx -efflux -target mutation -target modification -drug modification & drug degradation Specific antibiotics can have multiple mechanisms of resistance Specific mechanisms can confer resistance to more than one class of antibiotics

Answer 4

gram-negative bacteria and mycobacteria（even lower permeability than gram negative） hydrophobic and impermeable and acts as a selective barrier Hydrophilic molecules and some hydrophobic molecules must enter through size-limited pores Primarily responsible for intrinsic resistance

Answer 5

Min resistance value of one species

Answer 6

• Antibiotics are pumped out of the cell (outer and inner membrane) and therefore cannot reach their targets • Major mechanism in gram negative bacteria • Complex “multi-purpose” efflux pumps • Can cause multi-drug resistance • Can be upregulate by antibiotics

Answer 7

• Can be due to **genetic mutation of the target gene** -gyrB (topoisomerase) mutations and quinolone resistance • Can be due to **enzymatic modification of the target structure** -Erm (methyl transferase) modification of 50S subunit and macrolide resistance • Can be due to **acquisition of a variant target with low affinity to the antibiotic** -Penicillin Binding Protein PBP2 with low affinity penicillin

Answer 8

• Enzymes secreted in periplasm that are highly effective at cleaving beta-lactam rings • Different beta-lactamases exist with different spectrum… now there are extended spectrum (ESBL) that can cleave cephalosporins and metallo-beta-lactamases can cleave carbapenems. Concerns: can be horizontally transferred Trying to make beta-lactamases inhibitor, give the inhibitor with antibiotics as the treatment

Answer 9

• Inactivation of aminoglycoside by adding additional moieties: -AMP by adenylyl transferases -PO3 by phosphoryl transferases - acetyl by acetyl transferases • This prevent proper binding of aminoglycosides to the 30S subunit

Answer 10

• Antibiotic overuse -Health, food and animal industries • Antibiotic misuse -Improper indications e.g treating viral infections with antibiotics • Insufficient length of treatment. E.g. Tuberculosis 结核病

Answer 11

livestock: enter environment human pee: enter environment india: cheap antibiotics

Answer 12

Bring antibiotics to everywhere

Answer 13

What type of compounds? • Improve existing compounds: chemical modification or combine therapy • Natural products • Synthetic compounds • New targets • Unknown targets but known drugs How to get a new compound? • Isolate and purify natural compounds • Chemical or biological synthesis • FDA-Approved non-antimicrobial drugs

Answer 14

• No new drugs were approved between 2003 and 2011 • No new classes approved in >20 yrs • No new targets • Not that many drugs • Minimal products from big pharma

Answer 15

Beta lactum

Answer 16

Beta lactum

Answer 17

Beta lactum

Answer 18

Beta lactum

Answer 19

Aminoglycosides

Answer 20

Aminoglycosides Used a lot for selection

Answer 21

Aminoglycosides