Antibiotic Resistance Flashcards
In 1956, 70% of staphylococcus aureus were resitant to PenG, how?
Aquisition of the gene for beta lactamase enzyme
What is methicillin?
Modified lactamase-resistant penicillin
What is MRSA?
methicillin resistant Staph Aureus
If MRSA were to live with other bacteria that are resistant naturally to other drugs such as vancomycin, what would happen?
Due to the exchange of genetic info between bacteria, there may be the development of vancomycin-resistant MRSA
What antibiotic do we normally give to treat MRSA?
Vancomycin
Name 6 mechanisms that bacteria can become resistant to antibiotics
- Drug inactivation (like with beta lactamase)
- Alter target or aquire new target of the antibiotic (e.g. mutated RNA pol means that antibiotics can’t bind to it any more)
- Overproduction of target
- Intrinsic impermeability
- Efflux pump (new or increased action of efflux pump)
- Metabolic by-pass
Describe one way which MRSA become penicillin resistant
MRSA aquired a whole new gene for a new target for the binding of all of the penicillins
Describe how trimethoprin resistance by target overproduction can happen
Timethoprin inhibits the second enzyme in the folic acid pathway but bacteria can become resistant by overproducing the precursor to outcompete trimethoprin
Describe the mechanism of vancomyocin resistance
- Vancomyocin usually binds to the peptidoglycan terminus D-ala-D-ala
- A new bacterial metabolic pathway causes a new terminus D-ala-D-lac
- So less vancomyocin binding
- So less disruption to peptidoglycan cross linking
Describe what natural antibiotic resistance is as opposed to aquired
Innate resistance is normally expressed by virtually all strains of a particular bacterial species.
Acquired resistance is gained by previously susceptible bacteria either through mutation or horizontally obtained from other bacteria possessing such resistance via transformation, transduction, or conjugation.
Describe the 2 genetic mechanisms involved in the transfer of bacterial antibiotic resistance
- Chromosome mediated
- Plasmid mediated gene exchange
What are non-genetic mechanisms in bacterial antibiotic resistance?
tolerance
Which type (gram) of bacteria is plasmid-mediated gene exchange more common?
gram negative
- transferred by conjugation
- multi-drug resistance
Name the 3 methods of gene transfer in bacteria
- Transformation
- Transduction
- Conjugation
Describe what bacterial transformation is
The take up of DNA fragments from the environment (like from dead organisms) this gene may carry virulence, drug resistance etc.
Describe what bacterial transduction is
This is via bacteriophage, can be very rapid through populations of bacteria
Describe what bacterial conjugation is
Bacteria come together and form a conjugal tranfer tube/structure to receieve DNA from one donor bacterium to a recipient bcterium
- conjugal tube may be encoded by a plasmid
What two agents do we have in co-amoxiclav?
Clavulanic acid binds to beta lactamase
- It has a very similar structure to penicillin with the beta lactam ring on the right
HOW do beta lactams cause disruption of the cell wall?
Bind to PBPs in the cytoplasmic membrane - these target proteins catalyze the synthesis of peptidoglycan (forms the cell wall)
- interfere with cross linking
Describe 3 ways that beta-lactam resistance can occur in gram -ve bacteria
- outer membrane porin mutation
- penicillin binding protein mutation
- beta lactamase enzyme is aquired
How does vancomycin resistance come around? And explain how vancomycin would normally work
Terminal D-ala-D-ala is changed to D-ala-D-lactate which prevents vancomycin from binding to inhibit crosslinking.
- aquisition of the van operon allows for a new metabolic pathway to produce the lac version
Describe 2 non-genetic mechanisms to become resistant to antibiotics
- Inaccessibility to the drugs
- Stationary phase (a phase of growth in vivo) may cause biofilms/vegetations
How can the production of biofilms cause a resistance to certain antibiotics - this is a non-genetic antibiotic resistance
Biofilms are NOT susceptible to inhibitors of cell wall synthesis as they are not using those enzymes anyway - so we have to use other antibiotics
Describe some ways that we can prevent/overcome antibiotic resistance
Example of how we have had to constantly change our drugs/treatments due to antibiotic resistance in Neisseria gonorrhoeae
What are CREs?
carbapenems resistant enterobacteriaceae
How have CREs come about?
Aquired the new gene ndm 1 which destroys antibiotics (metalloprotease)
What is horizontal transmission?
In general, transmission of viruses can occur through two pathways: horizontal and vertical transmission.
In horizontal transmission, viruses are transmitted among individuals of the same generation, while vertical transmission occurs from mothers to their offspring.
What is antibiotic stewardship and why is it important?
Antibiotic stewardship is the effort to measure and improve how antibiotics are prescribed by clinicians and used by patients.
Improving antibiotic prescribing and use is critical to effectively treat infections, protect patients from harms caused by unnecessary antibiotic use, and combat antibiotic resistance.
