J Letchford Lec 2 Resistance Flashcards
List two Multi-drug resistant organisms…
1)
2)
1) E.coli
2) M. tuberculosis
List some of the following organisms of concern regarding resistance…
Enterococcus \_\_\_\_\_\_ Staphylococcus \_\_\_\_\_\_ \_\_\_\_\_\_\_ pneumoniae \_\_\_\_\_\_\_ buamanii Pseudomonas \_\_\_\_\_\_\_ Enterobacter
Enterococcus Faecium Staphylococcus Aureus Klebsiella pneumoniae Acinetobacter buamanii Pseudomonas aeruginosa Enterobacter
Antimicrobial resistance is either _____ or _____.
Innate or Acquired
Genetic mutations can lead to Antimicrobial resistance.
Most mutations confer ___ level resistance.
SOME produce resistance to 1 antibiotic e.g
S_____mycin resistance
Tri_____rim resistance
Some types of penicillin resistance
LOW
Streptomycin resisntace
Trimethoprim resistance
Another type of genetic antimicrobial resistance is the acquisition of New Genetic Material.
Mostly acquired on ______ through _____.
e.g _____ encoded ampicillin resistance
Plasmids
Conjugation
Plasmid
If a bacterium is coated in a matrix biofilm then this can lead to _____.
This is _____ if the biofilm is removed.
Resistance
Reversible
Multi-drug resistance plasmids accumulate ______ and can be transferred between bacteria by ______.
Transposons
Conjugation
Bacterial conjugation occurs when a donor with a mobile plasmid injects it’s _____ into a recipient bacterium.
The transferosome interacts with the relaxosome and two new donors are formed.
Pilus
What are the three mechanisms of antimicrobial resistance?
Inactivate/modify drug (antimicrobial)
Alter drug (antimicrobial) target site
Alter drug (antimicrobial) uptake/exit
Resistance to B-lactam antimicrobials can occur through:
Drug _______.
The group of enzymes that inactivate these antimicrobials are _ ______. They break open the B-lactam ring which is responsible for the drugs action.
Resistance can be ______ (s.aureus, p. aeruginosa) or plasmid-______ (e.coli)
Inactivation
B-lactamases
Chromosomal
Plasmid mediated
Extended spectrum B lactamases (ESBL’s) can be problematic as they inhibit lots of different _____ of beta lactams.
Classes
The periplasmic space is WHAT?
- The space between peptidoglycan layer and outer membrane (in gram negative bacteria)
B-lactamase is present in Gram-negative bacteria WHERE?
Periplasmic space
B-lactamase is produced inside the bacterium and released into the medium in the surrounding environment in Gram-____ bacteria.
Positive
B-lactamase inhibitors include…
Sul____
Cl___ _____
Taz____
They have a similar structure to B lactams but have no antibiotic activity.
Sulbactam
Clavulanic acid
Tazobactam
Resistance to B-lactams can occur due to alteration of the _____ ____.
Alteration of _____-____ ______ (PBPs) occurs.
This is due to mutations.
Target site
Mutation of the PBP2 leads to methicillin resistance in S.____ (____)
Mutation of the PBP3 leads to resistance in Haemophilus ______.
Mutation of the PBP1 leads to resistance in Streptococcus _______.
S.aureas (MRSA)
Haemophilus influenzae
Streptococcus pneumoniae
Resistance to B-lactams can occur due to altered _____ of the antimicrobials.
In gram negative bacteria the hydrophilic B-lactam drugs enter through ______.
In resistant bacteria, there is often a reduced number or size of _____.
Uptake
Porins
Porins
Resistance to Vancomycin (glycopeptides) occurs due to alteration of the ______.
There is a change in the terminal __ of the peptide chain.
D-ala-D-ala to D-ala-D-_____.
This results in an unstable complex with only _ H bonds forming between the Vancomycin and target site compared to the usual stable complex when D-ala-D-ala is present with _ hydrogen bonds.
VRSA!
Alteration of the target site
Amino Acids
Lactate
4
5
Resistance to inhibitors of nucleic acid synthesis (________ , ______) can occur due to alteration of the ______ ______.
Sulfonamides
Trimethoprim
Target site
Sulphonamides usually work by inhibiting ____ ____ synthesis. BUT resistance can occur when plasmids encode for enzymes with reduced affinity for the drug.
Sulphonamide usually inhibits the synthesis of _______ ____ which is needed to make up bases but resistance means the enzyme it usually inhibits has a weaker affinity for the drug so synthesis continues.
Nucleic acid synthesis
Tetrahydrofolic acid
Trimethoprim competitively inhibits _______ ____ (DHFR) and resistance can be caused by over-production of host DHFR and mutations within the structural gene for DHFR and acquisition of the DFR gene encoding a resistant form with reduced ______ for the drug.
Dihydrofolate reductase
Affinity
Resistance to aminoglycosides (Gentamycin etc) occurs often by drug ______.
The aminoglycosides are hydrophilic ____ possessing a number of ____ and ____ substituents. Clinical resistance occurs when structural modifications of the aminoglycoside takes place by enzymes expressed in resistant organisms. This compromises their ability to interact with r___.
This is carried out by enzymes called:
- Adenylylase adds ___ group
- Phosphorylase adds ____ groups
- Acetlyase adds _____ groups
Inactivation
Sugars
Amino
Hydroxy
rRNA
AMP groups
Phosphate groups
Acetyl groups
Resistance to antimicrobials can occur due to increased ____ of drugs.
Antibiotics are _____ ___ of the cell.
e.g Tetracycline, quinolones
This means that the drugs will not reach ___ concentration.
Some efflux pumps excrete a wide range of compounds simultaneously - this is seen in gram-+ve and -ve bacteria.
e.g (AcrAB.TolC) E.coli, (MexAB.OprM) P.aeruginosa, (QAC pump) S.aureus
Efflux
Pumped out
Optimum
Chromosomal multiple-antibiotic resistance (___)
e.g AcrAB/TolC ___ pump in E.coli
Widespread resistance to multiple solvents, detergents and antibiotics
Partly under control of MAR ____.
marA - activator
marR - repressor
Inactivation marR induces mar phenotype and up regulates the ____ pump which pumps out the antibiotics
MAR
Efflux
Operon
Efflux
