antibiotics, therapy, and resistance

B lactams

• block syn of peptidoglycan by cleaving B-lactam ring

• examples: penicillins and cephalosporins

inhibition of cell wall syn

• penicillins

• cephalosporins

inhibition of protein syn

• aminoglycosides

• tetracyclines

• chloramphenicol

• macrolides

• antisense nucleic acids

disruption of cytoplasmic membrane

• polymyxins

inhibition of general metabolic pathway

sulfonamides

inhibition of DNA/RNA syn

rifampin

B lactams

• block syn of peptidoglycan by cleaving B-lactam ring

• examples: penicillins and cephalosporins

• most effective against young growing cells (log phase)

penicillins don’t penetrate what?

the outer membrane (LPS layer) making them less effective against gram - bacteria

a cell w a damaged cell membrane dies from?

lysis

polymyxins

• interact w phospholipids creating leakage, particularly in gram - bacteria

• bind to phospholipids

what toxic effects can polymyxins have?

• renal fxn and can cause respiratory paralysis

• usually only topical but use to combat antibiotic resistant strains

rifampin

attacks RNA polymerase during transcription; may block syn of nucleotides or stop transcription

replication

DNA to DNA

transcription

DNA to RNA

translation

RNA to proteins

Antibiotics usually have a selective action against prokaryotes but…

can also damage eukaryotes because mitochondria have 70S ribosomes

Streptomycin & gentamycin

insert on sites on the 30S subunit and cause incorrect reading of the mRNA code

tetracyclines

block attachment of tRNA on the A acceptor site and stop further synthesis- binds 30S subunit blocks tRNA docking

blocking translation → 30S No protein syn =

cell death

chloramphenicol

Binds to 50S portion and inhibits formation of peptide bond

erythromycin

Binds to 50S and blocks movement of the ribosome

tetracyclines

Interfere with attachment of tRNA to mRNA–ribosome complex

Gentamycin & Streptomycin

Changes shape of 30S portion, causing code on mRNA to be read incorrectly

sulfonamides

lock enzymes required for folic acid synthesis

needed for DNA and RNA synthesis.

competitive inhibition

competes for active site on enz; shape of drug is so similar to the substrate it stops it from binding

humans acquire folic acid from?

sulfa drugs bc we lack this metabolic pathway

disk diffusion method

etermining the activity of antimicrobials

Adaptive response in which microorganisms begin to tolerate an amount of drug that would ordinarily be inhibitory=

due to genetic versatility or variation

acquired assistance

– spontaneous mutations in critical chromosomal genes

– acquisition of new bact genes

conjugation

transfer of DNA from 1 bact to another via pili; plasmid via pilus

transduction

acquiring DNA via bacteriophage transfer; virus transfers gene

transformation

taking up free DNA from the environment; picks up DNA (plasmid) from the environment

Mechanisms of Drug Resistance- due to new gene expression=new proteins with new protein expression

1. Decreased permeability to drug = blocked entry

• Change porins or block receptor

2, Drug inactivation by acquired enzymatic activity

• penicillinase- cleaves beta lactam ring

3. Change in drug receptors

• blocks drug binding site on target

4. increased elimination of drug from cell

• protein pumps drug out

5. Change in metabolic pathway

• New enzyme bypasses blocked enzyme

beta lactamase

cuts the beta lactam ring

Misuse of antibiotics selects for resistance

mutants includes:

– Using outdated or weakened antibiotics

– Using antibiotics for the common cold (virus) and other inappropriate conditions

– Using antibiotics in animal feed

– Failing to complete the prescribed regimen

– Using someone else’s leftover prescription

In hospitals

• despite efforts to maintain sanitary conditions a

hospital provides:

• A lot of sick people in close proximity= ↑transmission

-ppl w weak immune systems

-multiple types of infection

-majority of ppl on antibiotic

• patients are usually more ill and have lowered resistance to infection

• use a variety of antibiotics: ↑risk of conjugation+others

Limit antibiotic use to situations in which?

recover is unlikely without antibiotic treatment

• Sensitivity tests should be done

• Complete antibiotic regime

Patients with an infectious disease should be?

isolated from other patients