antibiotic resistance Flashcards

1
Q

for an antibiotic to be effective there must be

A

essential target susceptible to a low concentration of the antibiotic
must penetrate the envelope and reach the target in an active form in a sufficient quantity

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2
Q

carbapenems

A

multiple modifiable groups
last resort antibiotic
b lactamases
resistance occuring in enterobacteriacae - carbapenemases

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3
Q

mechanisms on resistance

A
antibiotic inactivation 
permeability changes 
efflux 
alter/remove target
metabolic bypass
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4
Q

intrinsic and aquired

resistance

A

intrinsic - outer membrane of gram negative bacteria - vancomycin cannot get into periplasm (1550 daltons)
acquired:
endogenous - mutation
exogenous - horizontal gene transfer of plasmids

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5
Q

antibiotic inactivation

A

b- lactamases
reduce concentration of active antibiotic
break bond in the b lactam ring - becomes penicilloic acid

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6
Q

use of antibiotics

A

adds selective pressure, will always drive resistance

Trilosan disinfectant now banned - increased resistance by inducing promoter mutations

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7
Q

reducing the concentration of active antibiotic in the cell - modification

A
aminoglycosides
phosphorylation
acetylation
adenylation  
bulky residues on antibiotic, no longer interacts with RNA/ribosome 

chloramphenicol is modified by acetyltransferases

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8
Q

permeability changes

A

outer membrane porins in gram negative bacteria size - less than 600 daltons
mycobacteria have mycolic acid - issue of hydrophillic antimicrobials - cannot get into cells (Isoniozid used)
pseudemonas aeruginosa resistant to Imepenem by reducing OprD porin protein expression. Coupled with cephalasporinase.
BUT porin deficient mutant less fit - nutrients cannot get in

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9
Q

efflux

A

gram negative bacteria
multiple substrates can be effluxed
ATP or anti-port (H+) driven
intrinsic or acquired
RND pumps are intrinsic in gram negatives (pump out bile acid)
RND spans periplasm (outer and inner membranes)
gram positives have efflux pump in cytoplasmic membrane, captures drug in cytoplasm or bilayer, pumps back into the environment

RND type - AcrAB-TolC complex spread cross outer and inner membrane
tripartite
TolC is porin,
AcrAB binds substrate and binds TolC
energy from antiport
multi drug resistance - penicillins, macrolides, fusidic acid
Pseudemonas and acinetobacter also have intrinsic pumps which bind multiple substrates
some inducable

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10
Q

alterations of target

A

altering concentration due to mutations in regulating genes - more target = more inhibitor required
alter affinity of drug for target by altering target

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11
Q

increase target concentrations

A

D-cycloserine resistance in Mycobacterium smegmatis
resistance by over production of target - enzyme alanine racemase
single mutation in the genes promoter region resulted in elevated gene expression
higher concentrations of antibiotic is required

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12
Q

target mutation

A

penicillin resistance by strep pneumonia
mosaicism- PBP DNA is combined with blocks of conserved sequences with blocks of variant sequences by horizontal gene transfer
reduced binding to penicillin

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13
Q

metabolic bypass

A

reliance on an alternative pathway to that inhibited

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14
Q

vancomycin resistance in enterococcus

A

metabolic bypass
expression of alternative pathway - produces D alanine D lac - reduces hydrogen bonding with vancomycin - reduced affinity by 10,000.

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15
Q

MRSA

A

associated with mobile genetic element MecA
encodes a new penicillin binding protein with decreased affinity for B lactams
still sensitive to vancomycin

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16
Q

VRSA

A

staph aureus acquired a transposon from a plasmid from vancomycin resistant enterobactericae.
Production of D ala D lac, vancomycin doesnt bind as much.
Action of multiple genes on the transposon e.g VanH pyruvate - lactate to produce lac
VanA ligates D-Ala D-Lac
VanX D-ala D-ala dipeptidase, removes D-alaDala

17
Q

Van-intermediate S.aureus

A

intermediate resistance due to increased amount of D ala D ala precursor, requires increased concentrations of antibiotic
all of vancomycin is used up before it reaches peptidoglycan division centre.
leads to VRSA