Antibiotics and Antimicrobial

Mode of Action got Protein Synthesis antimicrobial

30S: Block initiation of synthesis, inhibits t-RNA going A to P site, incorrect amino acid added to peptide chain

50S: Macro- premature release of tRNA intermediates. Linco: interrupt chain initiation

Tetracycline: 30 S at A site

Aminoglycoside: 30S at P site

Mode of action: Metabolic pathways

SULFONAMIDES: Inhibit dihydropteroate synthase

Trimethoprim: inhibit dihydrofolate to prevent conversion to dihydrofolic acid to tetrahydroloic acid

Possible general targets for antimicrobials?

Cell wall, plasma membrane, ribosomes, metabolic pathways, DNA synthesis

Specific targets for antimicrobial targeting cell wall?

Beta-lactams, glycopeptides, bacitracin

Specific targets for DNA synthesis

Fluoroquinolones (floxacin)

Specific targets for plasma membrane for antimicrobials?

Polymyxins and lipoprotein

Specific targets for ribosomes for antimicrobials?

30S subunit, 50S subunit

Specific targets for metabolic pathways for antimicrobials?

Folic acid synthesis (sulfo-), mycolic acid (izoniazid)

Definition of intrinsic resistance

Innate ability to resist antimicrobial activity

Causes of intrinsic resistance:

Lack of affinity to bacterial target, inaccessibility of antibiotic to bacterial cell, extrusion of antibiotic, innate production of enzymes that inactivate

Definition of acquired resistance

Obtain the ability of antibiotic resistance through chromosomal mutations and resistance gene acquisitions

How acquired genes are transferred to the bacteria?

Conjugation, Transformation, Transduction

Transduction

Gene is transferred from one germ to another

Conjugation

Gene transferred between germs when they connect

Transformation

Genes released from nearby germs can be picked up directly

Types of mobile genetic elements

Phases, transposons, plasmids

Mechanistic effects for antibiotic resistance on cell by Beta-lactams?

Efflux pumps and enzyme inactivation

Mechanistic effects of fluoroquinolones of antibiotic resistance?

Target modifications, efflux pump, blocked penetration

Target protection protein arm

• bind to antibiotic target

• remove antibiotic from the target

• mediate also steric dissociation

• Conformational changes to allow target protein to function

Make enzymes that inactivate antibiotic arm

• hydrolysis functional group

• Destroy its antibacterial activity

• Modify by covalent

Steps of enzymatic inactivation of antibiotic

Hydrolysis, group transfer, and redox process

Another strategy in the arms race bacteria has come up with against

Makes enzymes that inactivate antibiotic

Strategy 3 bacteria uses stategy for antibiotic resistance?

Target is redundant and replaces with another that sequesters antibiotic and the target in overproduced