INF1 - F. RESISTANCE MECHANISMS-COVERED Flashcards
what is antibiotic resistance
when bacteria survive exposure to 1 or more antibiotics
what is intrinsic resistance
natural resistance of a bacterial species to antibiotics
1. lack of target
2. lack of permeability
what is acquired resistance
develops in previously sensitive cells following mutations or transfer of genetic information (plasmids) between cells
- conjugation: sexual contact between bacteria
- transformation: DNA from environment through bacteria which have been damaged
- transduction: DNA transferred from 1 bacterium to another by a bacteriophage (virus)
4 mechanisms which cause resistance
- reduced cellular uptake
- inactivation of antibiotic
- alteration/mutation of target/increased expression of target
- increased efflux of antibiotic
what causes reduced uptake
has a negative charge, can reduce uptake due to LPS, mycolic acid of gram -ve outer membrane
what causes inactivation
beta-lactamases made by bacteria in response to beta-lactam antibiotics
what causes altered target
- mutation (PBPs)
- alternative pathway so bacteria can still achieve its metabolic process
- increased expression of target
what causes efflux
multiple types of pumps
varied expression/activity
what causes resistance to beta-lactam antibiotics
- beta-lactamases (mainly in gram-ve bacteria)
- few beta-lactam resistant bacteria don’t produce beta-lactamases
- target modification (PBP mutation)
- reduced uptake
how are beta-lactamases produced
genetic transfer and subsequent expression of the enzyme
>300 types
what drugs were developed due to lactamase-producing strains
- 3rd gen cephlasporins
- lactamase inhibitors: clavulanic acid with amoxicillin - co-amoxiclav
how does clavulanic work as a decoy
- possesses a beta-lactam ring but not active and hence a decoy target for lactamase enzyme which binds to molecule and inhibits enzymes
- only effective against serine beta-lactamases
what are extended spectrum beta-lactamases
- mutant lactamases that inactivate most/all beta-lactam antibiotics (mainly gram-ve)
- mutations are easily transferred to other bacteria via conjugation
- extrachromosomal DNA on plasmids - genes that encode molecules that are important in pathogenicity and also resistant to antibiotics ie - production of beta-lactamases
- produced by klebsiella app. and Escherichia coli strains
- many ESBLs not inhibited by clavulanic acid
- example of counter adaptation by bacteria
how does resistance to PBPs occur
- genetic transfer and subsequent expression of genes
- that lead to expression of mutated PBPs (MRSA, C. diff) and antibiotic no longer binds
how does a change of outer membrane permeability cause resistance to beta-lactams
- porins in OM of gram -ve bacteria
- decreased porin expression or mutations
- LPS confers a -ve charge, impedes entry of beta-lactams due to charge effects and hydrophobicity
