What is antibiotic resistance?
the ability for bacteria to survive treatment by certain antibiotics
Why is the antibiotic resistance problem so bad?
- people not taking complete course of antibiotics
- inappropriate prescriptions
- non therapeutic uses of antibiotics: to treat sick animals, biocide use, aquaculture
How do bacteria become resistant to antibiotics?
1) make enzymes which alter/destroy the antibiotic
2) alter the target site
3) prevent antibiotic from entering the cell
4) pump the antibiotic out of the cell
5) change their metabolism and become dormant
Explain what Beta Lactamases are and how they work
- enzymes that destroy antibiotics
- work by hydrolysing the B-lactam ring in the antibiotic rendering it ineffective = produces broad spectrum resistance
- gram negative b lactamases are excreted
What are extended spectrum b-lactamases?
-confer multi resistance
-inhibit a wide range of b-lactams
- resistance to penicillin but not extended spectrum cephalosporins
- derive from genes for TEM-1 and TEM-2/ SHV mutations
Which type of bacteria release B-lactamases outside their cells?
Gram negative bacteria
Which acid is combined with certain antibiotics to improve their effectiveness?
Clavulanic acid - blocks certain B-lactamases
What are efflux pumps and what do they do?
- actively pumps the antibiotic out of bacterial cells using ATP (active transport)
- carries out adaptive resistance
- powered by ATP hydrolysis
- located in cytoplasmic membrane
- comes in five superfamilies: MFS/ABC/SMR/RND/MATE
- ultimately reduces drugs concentration inside bacterial cell
Where can efflux pumps be encoded onto and what affect does this have?
- onto chromosomes and plasmids
- leads to intrinsic/ acquired resistance -> broad spectrum resistance
Why are efflux pump inhibitors not used?
because they are toxic and disrupt proton motive force
How do bacteria change their metabolism to evade antibiotics?
escape effect of antibiotic without undergoing genetic change, persister cells form, tolerate antibiotic.
metabolism can be changed due to metabolomics
Why do bacteria reduce their OM permeability?
to reduce amount of antibiotic coming into the cell, modifying porin channels allows selectivity
What is the function of persister cells?
-when bacterial cells change their metabolism they form persister cells
-don’t grow in presence of antibiotic but they tolerate it
What mechanisms do bacteria have to prevent antibiotics from entering their cells?
1) outer membrane permeability is reduced
2) bacteria can alter porin size/selectivity to block certain antibiotics from entering
