Antibiotics Flashcards

Question

1. Inhibition of BACTERIAL Cell Wall BIOsynthesis

Answer 1

Antibiotic groups: B-lactams, glycopeptides -Cell wall not in mammal cells is needed for bacterial cell therefore good target by antimicrobials

Answer 2

-part of bacterial cell wall that that is synthesized in 4 stage process beta lactams join with enzymes (PBPs) that are involved in cross linking in final form of peptidoglycan -beta lactams affect stage 3, 4

Answer 3

both have multilayer cell wall structure with inner cell wall membrane GP - thicker petidoglycan layer GN- have another outer membrane seperated by a periplasmic space which has phospholipids, lipopolysaccrides and porins GN- Beta lactams need to pass through the porins to reach the PbP -effect on cell depending on agent and effect of PBP involved

Answer 4

-active moiety (functional group) is the 4 member B lactam ring -ring interferes with cell wall production -complexes with PBPs which will inhibit cell division forming long filamentous forms and formation of cell wall deficient type that will lyse under osmotic pressure vanco and glycopeptides

Answer 5

Carbapenem - beta lactam class -against GN broad spectrum -not active against MRSA or VRE -stable against most B lactamases including ESBL and extended spec. -can get through porin channels that other drugs cant expensive -can cause seizures

Answer 6

Carbapenem -- beta lactam class More soluble and more rapidly absorbed Less adverse effects

Answer 7

-blocks transpeptidation step -decrease peptidoglycan layer -targets step 3 and 4 of peptidoglycan biosynthesis of dividing bacteria. Decreased peptido are defective and can cause cells to lyse -cannot cross the outer layer of GN bacteria so its limited to GP orgs like Staph, Enterococcus, or Strepto vanco and glycopeptides -cannot cross the outerlayer of GN bacteria the porins because they are too big -NARROW SPECTURM

Answer 8

Antibiotic group: Quinolones/Fluoroquinolones -topoisomerases I-IV are essential enzymes for DNA replication. They help control DNA topolgy (construction, twist), replication and cleavage of 2 units at the end of DNA replication -Quinolones target topos 2 in Gn and 4 in GP but not both however newer ones can 2 control DNA gyrase 4 control DNA topology

Answer 9

-used to treat pneumonia -increased risk of MRSA and C diff colonization -interfere with RNA/DNA used in chemo good to treat - staph, strep, entero, neisseria

Answer 10

transcription forms mature mRNA and structural RNA - Mediated by RNA polymerase (tetramer) with ABtics targeting different subunits (4) -can be used to treat meningococcal prophylaxes Rifampin is a synthetic AB but it is used in a combination with other drugs to treat TB , Staph, S.pnuemo because on its own it can reduce its efficacy overtime and preventing resistant strains from surfacing

Answer 11

Tetracyclines, aminoglycosides – target 30S Macrolides, lincosamide, chloramphenicol – target 50S 30S and 50S rsubunits bind to mRNA before translation occurs. Translation is mRNA into functional proteins = protein synthesis

Answer 12

-bind to 30S = mistranslation -production of aberrant proteins incorporated into the cell wall resulting in leakage and increased AB penetration Nephrotoxic (kidney) and ototoxic (hearing)

Answer 13

-Polyketide class – targets 30S subunit -REVERSIBLY inhibits protein synthesis by blocking peptide chain elongation -not for 18 as it impacts bone growth and causing yellowing of teeth in those under 8 -not for pregnant women because it can interfere with fetal bone growth

Answer 14

-binding to 50S rsubunits blocks peptide chain elongation inhibiting protein synthesis -prevent its assembly E.g. Erythromycin, Clarithromycin, Azithromycin

Answer 15

-Bind 50S ribosomes blocking initiation step of protein synthesis -prevent its assembly

Answer 16

binds 50S ribosome -Clindamycin to treat Staph and Strep, TSS by blocking the M protein of Staph, treat protozoan infections, toxoplasma and malaria

Answer 17

-interference of intracellular anabolic processes -folic pathway provides precursors needed in DNA biosynthesis - mediated by 2 enzymes: dihydropteroate synthase and dihydrofolate reductase E.g. sulfamethoxazole and trimethoprim (SXT) UTI due to Enterobacteriaceae Gastrointestinal, Respiratory

Answer 18

competitively inhibits the binding of para aminobenzoic acid with dihydropteroate synthase

Answer 19

blocks THF formation by preventing the action of dihydrofolate reductase

Answer 20

-treat mixed infections or anaerobic infections -prevent ABtic resistance -so we can use less of each AB to prevent toxicity -work with Synergism, Antagonism, Indifference

Answer 21

-combo therapy is better against the org than agent alone -used in V strep to treat endocarditis with Peni + Gentamicin therapy uses agent active on the cell wall to increase aminoglycoside uptake -when you see an enhanced zone between orgs is an indication of synergy

Answer 22

using peni (active on the cell wall and needs orgs to replicate) and tetraclyine (bacteriostatic and wont let the org replicate) together is worse than using them alone when the ZOI stops before it reaches the other zone for the next drug like a blunting

Answer 23

combined therapy is no better than drug alone

Answer 24

-over using ABtic - TOO LONG -using the wrong dose -when antimicrobials are used in animal feed or aquaculture -globalization Selection pressure - only strongest survive, susceptible bacteria removed Continuous development - findings to offset resistance, slow , global concern

Answer 25

resistance against S aureas then to GC

Answer 26

GC resistance followed by meningococcal resistance

Answer 27

used to treat Peni resistant S aureas

Answer 28

-treats peni resistant and clozallini resistant S aureus -no alternatives to fight infections by S aureus and Enterococcus

Answer 29

-decrease AB use -Dr should ration -control vet use - live stock -antimicrobial stewardship -using nanotechnology Encapsulating drugs allows for more surface modification and stabilization for longer

Answer 30

vancomycin resistance genes from Enterococcus faecalis could be transferred by horizontal gene transfer to S. aureus in experiments in vivo and in vitro -transposon on plasmid confers vanA-type vancomycin resistance in enterococci.

Answer 31

-natural members of species , passed vertically to progeny cells - predictable -bacteria differs in cell wall composition differences in resistance and susceptibility -resistance can be hydrophobic or hydrophilic nature of Abtic -resistance can depend on cell wall impermeability to AB, formation of biofilms and efflux -intrinsic resistance can also be chromosomally mediated enzymatic inactivation of antibiotics that penetrate the cell wall

Answer 32

1-Lipopolysaccharide composition (lipid + polysacc joined by covalent bond found in GN) 2-composution of outer membrane proteins OMP called porins. They all nutrients in and waste out , restrict influx of ABtics Natural and passed vertically to progeny -in GNb outer membrane is impermeable to large molecules like Vanco whereas Lactobacillus does not have a cell wall precursor which allows Vanc to bind and inhibit wall synthesis

Answer 33

Example 1: Vancomycin vs. GN (Ab too large to enter wall) Example 2: Vancomycin vs Leuconostoc and Lactobacillus (Organism w/o cell wall precursor target for vancomycin) Example 3: Enterococci – low levels of penicillin (Organism has PBPs with low attraction for penicillin) Example 4: Pseudomonas – lots of Ab (impermeable OMP; OMP + efflux system)

Answer 34

-irreversible attachment of orgs on surface can be single or multiple species -they form a matrix in nutrient rich environment increasing metabolic efficiency -outside of matrix protects the replication on the inside from ABtic exposure can be: Innate -part of biofilm pathway with presister cells found deep in the biofilm differentiating into a phenotypically resistant state - slow grower induced -induced by exposure have potential to produce biofilm but its not turned on until AB exposure

Answer 35

-efflux pumps found in GN and GP -natural in both susceptible and resistant -transporter proteins that remove toxic substances from within cells -resistance to antimicrobial agent, class, or cross resistance = multidrug resistance

Answer 36

most common resistance mechanism production of enzymes that destory ABtics before they reach the target B-lactam Ab bind to PBPs – Organisms can continue to produce cell walls Enzyme opens or cleaves the beta-lactam ring which makes it unable to attach to the PBPs (penicillin-binding proteins) Beta lactamase hydrolyze β-lactam antibiotics 4 classes: A,B, C,D Class B: metallo-based mechanism of action requiring zinc ions to disrupt β-lactam ring Class A,C,D: Serine-based mechanism -structure between PBPs and Classes A,C,D beta lactamases similar = may have evolved from PBPs

Answer 37

-distinct from parent - horizontal transfer of pre existing genes -Efflux (via plasmids)–Streptococcus macrolide resistance -Acquisition of new targets MRSA acquired staph cassette chromosome mec (SCCmec) =Methicillin resistance which encodes a PBP2A with reduced affinity to B lactams Resistance to Sulfonamides in GP and GN; new enzyme in folate pathway not affected by AB some can use both in and extrinsic

Answer 38

-Chromosomal mutation (transformation and recombination) -found in quinolones -Enzymatic target site alteration -ERM gene confers macrolide resistance found on plasmids and transposons -VRE (both vanA (highly onto MRSA), vanB confer vanc resistance) vanA transmissibility is a concern because it transmits resistance from Enterococcus to Staph

Answer 39

-Plasmid mediated β-lactamase resistance like on Extended spectrum beta lactamases (ESBL) for GN infections some aminoglycoside resistant antibiotics can produce an enzyme that prevents recognition of the 16S binding site (and therefore no inhibition of mRNA translation)

Answer 40

Lateral Gene Transfer (LGT) -spreading Ab resistance -physical movement of DNA and incorporating it in the recipient genome -Transduction, conjugation, transformation using plasmids, transposons, insertion sequences abd integrons

Answer 41

poly mixin

Answer 42

RNA polymerase

Answer 43

Nalidixic acid Flouroquinolones

Answer 44

essential metabolites by targeting enzymes in the folate pathway

Answer 45

some bacteria can produce b lactamase which can destroy or hydrolyze b lactam ring -PBP and serine have similar structure since they are kinda the same B lactam drug can bind to either. if they bind to the beta lactamase they will be destroyed . GN the beta lactamase is found in the periplasmic space and GP orgs they are released from the cell