11. Antibiotic resistance Flashcards
What is antibiotic resistance?
- ability of bacteria to survive treatment by certain antibiotics
- bacteria which are resistant to multiple antibiotics are called multi-drug resistant
Why is the problem of AMR so bad?
- people not taking complete courses of antibiotics
- inappropriate prescriptions or over-prescription of antibiotics
- novel therapies are now needed to combat antibiotics resistant infections
What are non-therapeutic uses of antibiotics?
- to treat sick animals
- as growth promoters in agriculture
- biocide use
- brewing
- aquaculture
- anti-fouling
How do bacteria become resistant to antibiotics?
- Make enzymes which alter or destroy the antibiotic
- Alteration of target site
- prevent antibiotics getting into the cell
- Pump (efflux) the antibiotic out of the cell
- Temporarily change their metabolism (dormancy)
How do B-lactamases alter and destroy the antibiotic?
- The B-lactamases (penicillinases)
- Adaptive resistance
- Hydrolyse the B-lactam ring
- Broad spectrum resistance mechanism
- gram negative B lactamases excreted
- some classes c an be inhibited by Clavulanic acid
How do ESBLs alter and destroy the antibiotic?
Extended spectrum B-lactamases
- discovered in 1980s
- plasmid-encoded (HGT)
- confer multi-resistance
- inhibit wide rang of B-lactams
- have resistance to penicillin but not extended-spectrum cephalosporins
- carbapenems used (resistance reported)
- derive from genes for TEM-1 and TEM-2 or SHV-1 by mutations in active site
What are ESBLs resistant to?
-TEM ESBL: E.coli, H.influenzae, K. pneumoniaea, N. gonorrhoeae
- SHV ESBL: K. pneumoniaea
How does the pump (efflux) work?
- energy dependent (active) transport of unwanted substances out of the bacterial cell
- adaptive resistance
- located in cytoplasmic resistance
- primary active transporters (H+)
- uniporters, symporters, antiporters
What are the 5 superfamilies of pumps?
MFS- Major facilitator superfamily
ABC- ATP-binding casette superfamily
SMR - small multi-drug resistance superfamily
RND- resistance-nodulation-cell division superfamily
MATE- multi-antimicrobial extrusion protein
What are efflux pumps?
They are used by bacteria to pump antibiotics out of the cell
- they didn’t evolve for antibiotics
What are the characteristics of efflux pumps?
- chromosomal or on plasmids (HGT)
- intrinsic or acquired resistance
- expression of several classes of efflux pump can lead to a broad spectrum of resistance
What are examples of some efflux pump inhibitors?
- Verapamil/ PABN/ CCCP
- function by disrupting H+ ions motive force- very toxic, no clinical application
What is triclosan?
- antibacterial and anti-fungal agent
- toothpaste, soaps, detergent
- select for broad spectrum efflux pump expressing bacteria (resistant to triclosan)
What happens at alteration of the target site?
example: DNBA gyrase and Fluoroquinolone resistance
- DNA gyrase- DNA synthesis
- fluoroquinolone block DNA-gyrase-DNA complex formation
- resistance by chromosomal mutations in both genes
- more common; mutations in GyrA
- prevent fluoroquinolone binding
Why do they have a temporary change in their metabolism?
