8. antimicrobial drugs and resistance Flashcards
these are agents used to treat diseases by destroying pathogenic microorganisms or inhibiting their growth at concentrations low enough to avoid undesirable damage to the host
antimicrobial agents
in 1928 _______ was discovered
penicillin
in 1935 ______ was discovered (not microbial produced)
sulfonamides
in 1940, _______ was first used in clinical as an effective therapeutic substance
penicillin
in 1944, _______ antibiotic was discovered from streptomycin bacterial species
streptomycin
are antibiotics primary or secondary metabolites?
secondary
today, 80% of the antibiotics are sourced from the bacterial genus ___________
streptomyces
between what years were most antibiotics disordered
1950-1980
do ideal antimicrobial drugs exhibit selective toxicity or non selective toxicity
selective toxicity
this is when the drug is harmful to the pathogen and not the host
selective toxicity
what are the 4 ways that a drug may act
- inhibition of cell wall synthesis
- inhibition of cell membrane function
- inhibition of protein synthesis
- inhibition of nucleic acid synthesis
this is when the drug inhibits transpeptidation enzymes involved in the building of peptidoglycan layers of the cell wall by cross linking NAG and NAM; as a result
- incomplete cell wall build
- cell will lyse and die
inhibition of cell wall synthesis
what are some drugs that are selective inhibitors of bacterial cell wall synthesis
- all beta-lactam antibiotics (penicillin, ampicillin, cephalosporins, cephamycin, carbapenems)
- vancomycin
- bacitracin
- novobiocin
- glycopeptide analogues (teicoplanin and cycloserine)
after inhibiting the transpeptidation reaction, some of the beta-lactam drugs are involved in __________ which leads to cell wall lysis
the inactivation of inhibitors of autolytic enzymes in the cell wall
T/F: gram positive and gram negative bacteria have different susceptibility to beta-lactam antibiotics due to structural differences in their cell walls
true
why do beta-lactam drugs show a remarkable lack of toxicity to mammalian cells
our cells do not have cell walls which is what these drugs target!
many pathogens gram positive and gram negative) show resistance to beta-lactam antibiotics due to their ability to produce __________: enzymes that inhibit or Destry beta-lactam compounds
beta-lactamases
know some beta-lactamases that are plasmid-mediated
- penicillinase of staphylococcus aureus, neisseria gonorrhoeae. haemophilus influenzae, enterococci
know some beta-lactamses that are chromosomally mediated
- bacteroids, acinetobacter, enterobacter, and pseudomonas species
a group of beta-lactamses called _________________________ confer additional resistance to more beta-lactam drugs such as cefotaxime, ceftazidime, or aztreonam; produced by certain species of gram-negative bacilli
extended-spectrum beta-lactamases (ESBLs)
ESBLs are produced by certain species of gram negative bacilli such as ____________ and __________
Klebsiella pneumoniae and Escherichia coli
what are some examples of Beta-lactamase inhibitors?
clavulanic acid, sulbactam and tazobactam
these have a high affinity for the beta-lactamses enzymes, they can bind to them and inhibit them rendering the beta-lactam resistant pathogen sensitive to beta-lactam drugs
beta-lactamase inhibitors
what are some examples of B-lactam/B-lactamase inhibitors
-amoxicillin/clavulanic acid (augmentin)
-ampicillin/sulbactam (Unasyn)
-piperacillin/tazobacterum (zosyn)
these drugs disrupt the membrane structure and permeability properties
polymyxins
these drugs interfere with biosynthetic functions of the cell membrane and inhibit teichoic acid synthesis
nalidixic acid and novobiocin
these drugs permit rapid diffusion of specific cations (such as potassium ions) through the membrane
ionophores (valinomycin)
this drug is a rapid bactericidal; it binds to the cell and causes depolarization of the bacterial membrane. this leads to intracellular potassium release which causes cell death
daptomycin
these drugs bind with the 30S subunit of the bacterial ribosome causing misreading of the mRNA and inhibiting protein synthesis
amuniglycosides (streptomycin and gentamicin)
these drugs bind ti the 50S subunits and inhibit the chain elongation
macrolides, azalides, ketolides and lincoasmide
- erythromycin’s, azithromycin, clarithromycin and roxithromycin
- the ketolide telithromycin
- the lincosamide clindamycin
these drugs binds reversibly to the 30S subunit of microbial ribosomes and interfere with aminoacyl-tRNA binding
tetracyclines
this drug binds to the 50S subunit
it interferes with the binding of new amino acids to the nascent peptide chain, through inhibiting peptide transferase
this drug is mainly bacteriostatic
chloramphenicol
these drugs possess a unique mechanism of inhibition of protein synthesis in gram positive bacteria
they interfere with translation by inhibiting the formation of N-formyl methionyl tRNA, the initiation complex at the 23S ribosome
oxazolidinones
this was the first oxazolidinone to be commercially available, and it is used to treat infections caused by vancomycin-resistant Enterococci and even Mycobacterial infections
lienzolid
this drug binds strongly to the DNA-dependant RNA polymerase of bacteria. it blocks bacterial RNA synthase
rifampin
these drugs inhibit bacteria DNA gyrases (topoisomerase) thus interferes with DNA replication, transcription and DNA repair mechanisms
quinolones and fluoroquinolones
these drugs inhibit the synthesis of nucleic acids
sulfonamides, trimethoprim and pyrimethamine
_______ are produced by beta-lactam-antiobiotic-resistant pathogens e.g. K. pneumoniae, staphylococci
beta-lactamases
__________ resistant pathogens produce adenylating, phosphorylating or acetylating enzymes that destroy the drug
aminoglycoside
how can micro-organisms change their permeability to the drug?
through down regulation of porin channels require for B-lactan entry; exhibit resistance to carbapenam antibiotics based on the loss of these porin channel proteins
_______ have a natural permeability barrier to aminoglycoside antibiotics
streptococci
what are some examples where microorganisms can develop an altered structural target for the drug?
- modification in PBPs (mutation or expression of alternative PBPs): this can lower the ability of beta-lactam antibiotics to bind to PNPs in the bacterial cell wall
- erythromycin resistant organisms have an altered receptor on the 50S subunit of the ribosome
in trimethoprim resistant bacteria, the dihydrofolic acid reductase (involved in nucleic acid synthesis) is inhibited far less efficiently than in trimethoprim susceptible bacteria. what is this an example of?
micro-organism can develop and altered enzyme that can still perform metabolic function but is much less affected by the drug
this process occurs in some multi drug-resistant gram negative pathogens; the upregulation of efflux pumps in concert with low membrane permeability confers the resistance to penicillin and cephalosporins as well as other antibiotics
micro organisms develop efflux systems that expel antibiotics out of the cell
