AMR Exam 2 full notes (-ESKAPE)

Abraham & Chain

Discovered penicillinases (1940)

Henrici

First described biofilms

Griffith

Genetic transformation experiment in mice

Clinical Resistance

MIC>toxic dose

bacteria type, infection site, pharmacokinetics, & immune response

WHO Importance Criterion

C1: AB is Sole Therapy

C2: AB treats bacteria from non human source

WHO Priority Criterion

C1: AB is sole therapy

C2: AB use induces resistance

C3: AB treats bacteria that can transmit resistance

Critically Important and Highest Priority ABs

Cephalosporins

Glycopeptides

Macrolides

Polymyxins

Quinolones

Biofilms mechinisms

Physical barrier

Persister cells

Stress AB

AB degradation

Biofilm efflux pumps

CA-MRSA

Healthy people

Curable

Highly Virulent

HA-MRSA

Immunocompromised

Resistant

Less virulent

Carriers, Vectors, & Pathogens

High capacity to transfer AB resistant genes

Carriers: environment

Vectors: non-clinical/clinical

Pathogens: pathogenic

Conjugation

HGT

F+ gives gene to F- (s strand)

Hfr: F+ into genome from plasmid

Transformation

HGT

uptake of naked DNA

recombination

Transduction

HGT

phage w/F+ DNA infects and gene gets incorperated

Vertical gene transfer

parent to daughter cell

ABT Enzymatic Modifications

Increase steric hindrance of AB

Nucleotidylation, phosphorylation, glycosylation, acylation, hydroxylation

ABT Sequestration

Release analogs to use up ABs

Capsular polysac, DNA, lipocalin, membrane vesicles

ABT Enzymatic degradation

Hydrolysis B-lactams

ampGRC

2CRS/TCRS

Linearization of Rifampin

ROX

Efflux pumps- Change in availability

Pump out

Constitutive or dependent

Efflux types

MATE

MFC

SMR

RND

ABC

Uses Na gradient

Uses H+ gradient

Uses H+ gradient

Uses H+ gradient

Uses ATP

Porins- Change in availibility

Loss of porins

Decreased expression

Structural change (narrow)

Cell Wall- Target Modification

substitutes d-ala-d-ala for d-ala-d-lac

Vancomycin resistance

Ribosome- Target Modification

50s: methylation and mutation of 23S

MLSB resistance

30S: 16S mutation

aminoglycosides/tetracycline resistance

Cell Envelope- Target Modification

Increase positive charge of phosphate backbone

Polymyxin resistance

Aminoarabinosylation, Lysinylation, Alanylation

Point Mutations- Target Modification

AA change to DHFR, DHPS, GyrA/ParC, and RNA polymerase

Target Replacement

Swap protein for one with same function but with more resistance PBP2a

Target Protection

Mfpa protects Gyrase

tetO unbinds tetracyclines

ABC-F protect ribosome

S. aureus produces open peptidogylcan

B-lactamase classes

A: serine-B-lactamases (serine)

B: metallo-B-lactamases (zinc)

C: cephalosporinases (serine)

D: oxacillinases (serine)

Extended Spectrum B-Lactamases (ESBL)

Plasmid encoded

Responsible for clinically resistant bacteria

Carbapenemases (KPC1, VIM, IMP, NDM1, OXA-48) are most dangerous

ampG-ampR-ampC

system to produce B-lactamase in gram neg

BlaR1, BlaR2, BlaI, BlaZ

TCRS to produce B-lactamases

ROX

Linearizes rifampin

OleB

mechanisms used to make macrolides outside of a cell

TolC-AcrAB

Parts of efflux pumps in gram negative (TolC: outer, AcrA: peri, AcrB: inner)

TetR, TetA

TC bing to tetR to allow tetA to make pumps

vanS, vanR, vanHAX

TCRS to convert d-ala-d-ala to d-ala-d-lac

erm genes

methylate 23S ribosome

Sul1, Sul2

create resistant DHPS analog

mecR, mecR2, mecI mecA

TCRS to produce PBP2a

Mfpa

Protein that mimics B-DNA and protects gyrase from quinolones

tetO

protein that unbinds tetracyclines from 30S rRNA

ABC-F

protect 50S ribosome from general ABs