Antimicrobial Resistance

Question 1

• Intrinsic resistance? E. Coli with penicillin? Mycoplasma with B-LActams?
• Tolerance? 2 examples?
• Porins: What species? Allow what to enter?
• Efflux pumps: Species? Chrom or plasmid? 1 pore = ? Which species has multiple efflux pumps? Type of resistance?
• Peptidoglycan: Precursor consists of? (3) Sugars linked by? Peptides linked by? What does the linking? What is then cleaved?
• Most important enteric GNR’s? (3) Bipolar struc?
• Most important non enteric GNR’s? long struc?

Answer 1

• Had resistance before ab; porin; no cell wall
• Escape; biofilm, stationary phase
• Gram negative; hydrophillic organisms
• Both gram positive and negative; can be either; 1 drug efflux; pseudonomas; intrinsic
• Glc-Nac linked to MurNac with 5 AA’s (last 2 D-alanine) on Mur-Nac; Transglycosylase; transpeptidase; PBP; D-alanine
• Enterobacter, Escherichia (E.Coli), klebsiella; kelbsiella
• pseudonomas; pseudonomas

Question 2

Beta-lactam resistance: What do beta lactams bind? At what step is inactivated? 2 ways resistance occurs?

• Narrow spectrum resistance: Species? (3) Resistant against?
• ESBL: Species? (2) Resistant against?
• ampC constit: Species? (2) Resistant against?
• KPC/NDM1: Species? (2) Resistant against?
  1. ) Narrow spectrum penicillinase: 3 species? gene? plasmid or chrom? All vs. few with it?
  2. ) ESBL: Mutants of? Usually on? Additional drug resistance? (2) Inhibited by clavulanic acid? Treat with?
  3. ) Broad spectrum: Gene? Located? 2 states? Species? (2) Not inhibited by? (2) What induce it? Inducible resistant to? Consitit. resistant to? Treat?
  4. ) Carbapenemase: Resistant to? KPC on what? Species? NDM1 species? Rarely on?

Answer 2

• PBP’s; Transpeptide linking; modify drug via enzymes; modify PBP target
• S. Aeurues, e.coli, kelbs; pen/amp
• E. Coli, Kleb; all pen, all cephs
• Enterobacter, pseudonoma; all pens all cephs
• Kleb, E. Coli (rare); all pens, all cephs, carban.
  1. ) Staph aeureus = bla = plasmid = all; e.coli = TEM1 = Plasmid = few; Klebs pneu = SHV-1 = chrom
  2. ) TEM 1/2 and SHV-1; plasmids of e coli and klebs; piper and all cephs; yes; Carbapenems
  3. ) ampC; chrom; inducible/constit.; GNR’s enterobacter and pseudonomas; C. acid and tazobactam; amp and cefazolin; amp and ceph 1; amp, all cephs, pip; carbap
  4. ) all beta lactams; plasmid of Kleb pneu; kleb. pneu; e.coli

Question 3

Altered PBP’s: Done how? (2)

1. ) Staph (all): Genes for this? endcodes? Leads to what? BL inhibitors work? What drug still works? How did this occur? Maybe from?
2. ) Enterococcus: E. Faecium: Mutation? Leads to?E. faecelius?
   - How does vancomycin work? Who is intirisically resistant? Why?
3. ) VanA: Leads to? Plasmid/chrom? What was the concern? Type of resistance? Found in what?
4. ) VISA/VRSA: Type of resistance? Done how? Increases what? Effect?

Answer 3

• Mutate current PBP or acquire new PBP
  1. ) mecA; PBP2A; MRSA; No; vancomycin; cassette picked up via transformation; viridians strep
  2. ) PBP5 mutation; overexpression; rare
• Bind PG precursor blocking PBP to link sugars; GNR’s via drug too big to enter pores
  3. ) D-Ala –> D-Lac; plasmid; go to staph; modified target; E. faecium
  4. ) Decreased drug interaction; less drug to bind precursor; increase D-ala to bind; thicker wall

Question 4

Macrolide resistance: Often found in? (2)
1.) MSR gene: Does what?
2.) erm gene: Type of resistance? Done how? 2 states? Clindamycin resistant to? Even if it says? Eryhtro resistant to? Test to check for this? If eythro resistant, don’t use?
Quinolone: Works by targeting what? (2)
- Resistance occurs via? (2) which is rare?
- Mutations occur slow and? To what region?
1.) Gram positive target? Drug that does this? Good for what?
2.) Gram negative target? Drug that does this? Good for what?
- If staph has R to Cipro (gyrA mutation), soon will be R to? On?
- If e.coli has R to moxi (ParC mutation), soon will be R to? On?

Answer 4

• Staph and strep
  1. ) Decrease interaction by effluxing drug
  2. ) Modify target by methylating 23s RNA; Inducible/Constit.; Constit state; Sensitive; both inducible and constit; D-Test; Clindamycin
• 2 subunits of DNA gyrase; 2 subs of DNA toposisomerase 4
• modified target via point mutations; rare decreased interaction via efflux
• Stepwise; QRDR region
  1. ) Topo 4; moxi; strep pneu
  2. ) DNA gyr; Cipro; pseudo
• Moxi; ParC
• Cipro; GyrA

Question 5

Bacterial Toxins:

• Toxin is a macromolecular product of microbes that do what? 2 ways?
• How can toxin be implicated? (4 ways)
• Liposaccharide toxin: Ex? On what? Leads to what?
• Antitoxin: Ab’s against the toxin are what? Response speed?
• Toxoid: Active? Do what? Leads to lasting?
• New therapetutic agents doing what?

Answer 5

• harm the host; alter structure or function
• purified toxin leads to disease; antitoxin stops disease; correlation b/n amount and virulance; mutant bacteria without toxin = no disease
• endotoxin; GN species; septic shock via PAMP
• Infused; immediate
• No; creates immune response; prophalaxis
• “A” part of toxin coupled to Ab to target cells you want to destroy

Question 6

Toxins: Bacterial proteins: Heat labile? Name?

1. ) Facilitate spread of microbe: Done how?
2. ) Damage cell membranes: Ex? Do what?
3. ) Induce excessive cytokines: Ex? Bind to what? Increases what? Ex? (2)
4. ) Interfere with protein synthesis leads to?
5. ) Alter cytoskeleton example?
6. ) Inhibit release of NT’s: What is inactivated? Ex? (2)
7. ) Interfere with signal transduction: Many target what? (2) Examples: Increase cAMP by increasing Gs pathway? Increase cAMP by inhibiting Gi in respiratory endo? Activate cGMP to induce diarrhea? Mimic adenylate cyclase (need Ca/calmodulin)? Cleaves MAP kinase kinase to cell death?

Answer 6

1. ) Break down ECM
2. ) Cytolysins; insert probe
3. ) Superantigens; Th non specifically; cytokines and inflammation; Staph Toxic Shcok, pyrogenic species
4. ) Kills cell
5. ) C diff alters GI epi
6. ) SNARE; Botulinum = Inhibit Ach release; Tatanus = Inhibit inhibitory NT’s from interneurons
7. ) Adenylate or guanylate cyclase; Cholera/ E.coli; Pertussis; E. Coli enterotoxin; Anthrax Edema Factor; Anthrax Lethal Factor

Question 7

• Penicillin Resistance: Occurance? Gene involved/ PBP? Mechanism? Drugs Targeted? Inhibitable?
  1. ) Staph?
  2. ) Strep pneu?
  3. ) Enterococcus faecium?

Answer 7

1. ) Common; mecA (PBP2a); mecA acquired which leads to PBP2a; ALL beta lactams; no
2. ) rare; PBP2x; picked up via TRANSFORMATION (maybe from strep viridians); ALL beta lactams; no
3. ) Few; PBP5; Mutation in PBP5 or overespression; ALL beta lactams; no

Question 8

• Vancomycin resistance: Occurance? Gene involved (where) ? Mechanism? Level of resistance? Inhibitable?
  1. ) S. Aureus?
  2. ) S. Aureus?
  3. ) E. faecium?
  4. ) E. faecalis?
• Quinolone resistance:
  1. ) Gram positive organisms?
  2. ) Gram negative organisms?

Answer 8

1. ) EXTREMEly RARE; VanA on plasmid; D-ala to D-lac; high level; No
2. ) Rare; multiple chrome genes altered; Increased cell thickness with more D-ala spots for vanco to bind; Low level; no
3. ) Few; VanA on plasmid; D-ala to D-lac; high level; No
4. ) RARE; VanA on plasmid; D-ala to D-lac; high level; No
5. ) few; parC more than gyrA; conformation change not allowing Flouroquinolones to bind; step wise process; no
6. ) few; gyrA more than parC; conformation change not all

Question 9

• Macrolide and Clindamycin Resistance:
  1. ) Efflux pumps: Species that develop this? (2) Plasmid or chromosome? drugs effected? Test for it?
  2. ) Methylase: Species? (2) gene? drugs effected? test for it?
• Erythromycin/clindamycin with macrolide efflux? macrolide methylase inducible? macrolide methylase con?

Answer 9

• Strep pneu and staph; chromosome; macrolides only; D-test is negative
• Strep pneu and staph; Erm; Macro and clindamycin; positive D test
• E: R, R, R
• C: S, S, R