Lecture 7 Flashcards
What are the non-genetic forms of antibiotic resistance?
Metabolic inactivity as many antimicrobials target metabolic processes of the bacteria so dormant cells will be unaffected
Lack of target structure
Exclusion by preventing an antibiotic from being able to reach its target molecule
What are the genetic forms of antibiotic resistance?
Chromosomal resistance and acquired genes
What are the 6 different mechanisms of antibiotic resistance?
Exclusion of the antibiotic from the site of action
Efflux pump for the removal of the antibiotic
Enzymatic modification of the enzyme to inactivate it
Destruction of the antibiotic via enzymes
Modified antibiotic insensitive target
New antibiotic insensitive target
What are beta-lactam antibiotics?
Molecules that inhibit peptidoglycan synthesis by irreversible inhibition of transpeptidase resulting in a poorly formed cell wall making the bacteria osmotically unstable and therefore lysing it and killing the cell
How are bacteria resistant to beta-lactam antibiotics?
Gram negative bacteria have intrinsic resistance to penicillin as it cannot penetrate the pores in the outer membrane (though several derivatives can)
Many bacteria have a beta-lactamase gene which produces an enzyme which can break the beta-lactam bond and inactivate the antibiotics
Some bacteria have a mutated transpeptidase which beta-lactams cannot bind to
What are extended-spectrum penicillins?
Penicillin-based antibiotics like amoxycillin that are able to pass through the pores in gram negative bacteria and are therefore effective against both gram positive and gram negative bacteria
What are beta-lactamases?
they are a large group of serine proteases with over 200 different types being known of with most being specific for an antibiotic group however some are zinc metallo enzymes with broad spectrum activity
How was beta-lactamase resistance overcome?
Development of resistant penicillins in the lab such as methicillin, oxacillin and nafcillin
What is staphylococcal cassette chromosomem mec?
A gene which allows for a transpeptidase which has a low affinity for beta lactams and is mainly found in gram positive bacteria
What is vancomycin?
An antibiotic of last resort which is active against methicillin resistance bacteria
it inhibits peptidoglycan synthesis by binding to the penta-peptides of the peptidoglycan monomers recognising a Ala-Alanine and binding to the last alanine preventing them from being used to make the transpeptidase link
What is VISA?
Vancomycin intermediate staphylococcus aureus which has mild resistance to vancomycin through alterations in the cell wall and reduced permeability
What are the mechanisms of vancomycin resistance by vancomycin resistant enterococci and staphylococcus aureus?
vanH which codes for a dehydrogenase of D-Lactate from pyruvate removing the ala-ala recognition site
vanA which codes for a ligase that forms D-Ala-D-Lac di-peptides
vanX dipeptidase that cleaves D-Ala-D-Ala dipeptides
vanY carboxypeptidase that cleaves off D-Ala from pentapeptide
What are the antibiotics that inhibit protein synthesis?
Aminoglycosides such as streptomycin Tetracyclines such as doxycyclne Lincosamides such as clindamycin Macrolides such as erythromycin Chloramphenicol These all bind to the ribosome to prevent protein synthesis
How are bacteria resistant to antibiotics that inhibit protein synthesis?
expulsion from cell (efflux pumps)
• mutational modification of rRNA
• mutational modification of ribosomal proteins
• enzymatic modification of rRNA (e.g. methylation)
• enzymatic modification of antibiotic
What antibiotics are inhibitors of nucleic acid synthesis?
Quinolones and fluroquinolones these bind to topoisomerases inhibiting DNA synthesis
