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INFECTION AND IMMUNOLOGY > J Letchford Lec 2 Resistance > Flashcards

J Letchford Lec 2 Resistance Flashcards

1
Q

List two Multi-drug resistant organisms…
1)
2)

A

1) E.coli

2) M. tuberculosis

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2
Q

List some of the following organisms of concern regarding resistance…

Enterococcus \_\_\_\_\_\_
Staphylococcus \_\_\_\_\_\_
\_\_\_\_\_\_\_ pneumoniae
\_\_\_\_\_\_\_ buamanii
Pseudomonas \_\_\_\_\_\_\_
Enterobacter
A 
Enterococcus Faecium 
Staphylococcus Aureus 
Klebsiella pneumoniae 
Acinetobacter buamanii 
Pseudomonas aeruginosa 
Enterobacter
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3
Q

Antimicrobial resistance is either _____ or _____.

A

Innate or Acquired

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4
Q

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

A

LOW

Streptomycin resisntace
Trimethoprim resistance

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5
Q

Another type of genetic antimicrobial resistance is the acquisition of New Genetic Material.

Mostly acquired on ______ through _____.

e.g _____ encoded ampicillin resistance

A

Plasmids

Conjugation

Plasmid

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6
Q

If a bacterium is coated in a matrix biofilm then this can lead to _____.

This is _____ if the biofilm is removed.

A

Resistance

Reversible

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7
Q

Multi-drug resistance plasmids accumulate ______ and can be transferred between bacteria by ______.

A

Transposons

Conjugation

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8
Q

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.

A

Pilus

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9
Q

What are the three mechanisms of antimicrobial resistance?

A

Inactivate/modify drug (antimicrobial)

Alter drug (antimicrobial) target site

Alter drug (antimicrobial) uptake/exit

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10
Q

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)

A

Inactivation

B-lactamases

Chromosomal

Plasmid mediated

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11
Q

Extended spectrum B lactamases (ESBL’s) can be problematic as they inhibit lots of different _____ of beta lactams.

A

Classes

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12
Q

The periplasmic space is WHAT?

A
  • The space between peptidoglycan layer and outer membrane (in gram negative bacteria)
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13
Q

B-lactamase is present in Gram-negative bacteria WHERE?

A

Periplasmic space

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14
Q

B-lactamase is produced inside the bacterium and released into the medium in the surrounding environment in Gram-____ bacteria.

A

Positive

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15
Q

B-lactamase inhibitors include…
Sul____
Cl___ _____
Taz____

They have a similar structure to B lactams but have no antibiotic activity.

A

Sulbactam
Clavulanic acid
Tazobactam

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16
Q

Resistance to B-lactams can occur due to alteration of the _____ ____.

Alteration of _____-____ ______ (PBPs) occurs.

This is due to mutations.

A

Target site

17
Q

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 _______.

A

S.aureas (MRSA)

Haemophilus influenzae

Streptococcus pneumoniae

18
Q

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 _____.

A

Uptake

Porins

Porins

19
Q

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!

A

Alteration of the target site

Amino Acids

Lactate

4

5

20
Q

Resistance to inhibitors of nucleic acid synthesis (________ , ______) can occur due to alteration of the ______ ______.

A

Sulfonamides
Trimethoprim

Target site

21
Q

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.

A

Nucleic acid synthesis

Tetrahydrofolic acid

22
Q

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.

A

Dihydrofolate reductase

Affinity

23
Q

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
A

Inactivation

Sugars

Amino

Hydroxy

rRNA

AMP groups
Phosphate groups
Acetyl groups

24
Q

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

A

Efflux

Pumped out

Optimum

25
Q

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

A

MAR

Efflux

Operon

Efflux

INFECTION AND IMMUNOLOGY (14 decks)

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