What is an antimicrobial agent?
a natural or synthetic compound that kills or prevents growth of bacteria or other microorganisms
What is an antibiotic?
An antimicrobial agent produced by a microorganism (natural)
How can antimicrobial agents be classified?
bacteriostatic, bacteriocidal, bacteriolytic
What does a bacteriostatic agent do?
inhibit growth but do not kill bacteria, impairment of growth reversed by dilution. Eg antimicrobials that inhibit protein synthesis
What does a bacteriocidal agent do?
kill bacteria. Some bacteriocidal agents lyse bacteria others don't. Toxicity is not reversed by dilution.
What does a bacteriolytic agent do?
Kill and lyse bacteria. Toxicity is not reversed by dilution. Examples include antibiotics that inhibit cell wall synthesis.
What must an antimicrobial do to be clinically useful?
inhibit bacterial growth at concentrations that are not toxic to human or animal cells
Less than ____ of known antibiotics are clinically useful
What is MIC (minimum inhibitory concentration)
lowest antimicrobial conc that completely inhibits bacteria growth.
How do you measure antimicrobial activity?
liquid culture: determines MIC (quantitative). Or solid culture.
What is solid culture?
disk diffusion technique. Disk of filter paper is soaked with an antimicrobial agent. Disk then placed onto an agar plate that was previously inoculated with a bacterium. Antimicrobial agent diffuses from the disk onto agar, creating a gradient, further from disk= lower conc of antimicrobial. If microbial= bacteriostatic, bacteriocidal a zone of inhibition results
What are some examples of synthetic antimicrobial drugs?
sulfa drugs, isoniazid, quinolones,
How do sulfa drugs work?
blocks synthesis of folic acid and interfers with nucleic acid synthesis, prevents growth of bacteria b/c they need to synthesise folic acid rather than getting it from diet
How does isoniazid work?
prevents growth of bacteria by inhibiting synthesis of mycolic acid, a cell wall component only found in bacteria. Though to inhibit NAD dependent enzymes involved in mycolic acid synthesis. Used to treat TB
How do Quinolones work?
Prevent growth of a wide range of gram positive and gram negative bacteria by inhibiting DNA gyrase, an enzyme critical for DNA structure and replication. Used for treating urinary tract infections.
Penicillin G and methicillin are active against ________ bacteria whereas ampicillin and carbenicillin affect ______
gram positive, gram positive and gram negative
What inactivates penicillin G, amphicillin and carbenicillin?
bacterial produced enzymes of the B-lactamase family. Methicillin is resistant to this
How do B-lactam antibiotics work?
inhibit cell wall synthesis, bind and inhibit penicillin binding proteins, enzymes that synthesise peptidoglycan. Inhibit the transpeptidation step of cell wall biosynthesis.
How does glycopeptide vancomycin work?
blocks the transpeptidation step of cell wall synthesis by binding to peptidoglycan itself (specifically the terminal D-ala D-ala dipeptide)
How does Rifampin/ rifampicin work?
inhibits the initiation step of transcription in bacteria by binding to RNA polymerase. Used in combination with isoniazid to treat TB, or with fusidic acid to treat MRSA
How do Aminoglycosides work?
Inhibit protein synthesis by targetting the small (30s) subunit of the ribosome (s12) protein. No longer used as bacterial resistance occurs frequently.
How do macrolides work?
inhibit protein synthesis by interacting with large (50s) subunit of the ribosome and blocking peptide bond formation. Examples: erythromycin used in patients who are allergic to penicillin
How do tetracyclines work?
inhibit translation by binding to the small (30S) ribosomal subunit. Tetracylines block binding of aminoacyl-tRNA to the A site of the ribosome. Inhibits growth of almost all gram positive and negative bacteria. Used in treatment of STDs, legionnaire's disease, anthrax
What are the 5 antimicrobial resistance mechanisms of bacteria?
impermable barrier, efflux pumps, chromosomal mutation conferring resistance, inactivation of antibiotic, lack of target for antibiotic
impermeable barrier- resistance?
impermeable to antibiotic. Most gram negative bacteria are impermeable to penicillin G
Efflux pumps- resistance?
Organism able to pump out an antibiotic entering the cell eg chromosomally or plasmid encoded efflux pumps for tetracycline, erythromycin
Chromosomal mutation conferring resistance?
eg mutations in genes coding DNA gyrase (resistance to quinolones), RNA polymerase (resistance to ritampicin) or S12 protein of small 30s ribosome subunit (resistance to streptomycin)
Inactivation of antibiotic- resistance?
Organism may be able to alter the to an inactive form. eg enzymatic phosphorylation of streptomycin, degradation of Penicillin G. Usually plasmid encoded.
Lack of target antibiotic- resistance?
The organism may lack the structure an antibiotic inhibits, eg mycoplasmids lack a cell wall and are therefore resistant to penicillins
What are plasmids?
extra chromosomal circular pieces of DNA that replicate i bacteria
How do R (resistance) plasmids confer antimicrobial resistance?
contain genes encoding proteins that confer antimicrobial resistance, referred to as R plasmids. Can be transmitted from one bacterium to another through genetic exchange (conjugation), thought to be one of the main ways resistance spreads.
Why is there rising rates of antimicrobial resistance?
inappropriate use of antimicrobials when treating patients, use in animal feeds, fish farming, fruit production