Antibiotic resistance 1 Flashcards

1
Q

Why has development of new antibiotics slowed?

A

Expenses, no new targets, short term use, safety profiles

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2
Q

Two categories of antibiotic resistance?

A

Intrinsic and acquired

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3
Q

What is intrinsic antibiotic resistance?

A

Resistance that is not acquired from any mutation and was there from the start

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4
Q

What is acquired antibiotic resistance?

A

Bacteria has seen antibiotic and bacteria has developed resistance over time

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5
Q

Innate part of intrinsic and acquired resistance?

A

Pumps can pump the antibiotic out of the bacteria to stop it from having its effects

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6
Q

Impermeable barrier part of intrinsic resistance?

A

Gram -ve bacteria have impermeable outer membrane that covers the peptidoglycan targets

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7
Q

Vertical gene transfer part of intrinsic resistance?

A

Gene transfer from parent to offspring

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8
Q

Gene amplification part of acquired resistance?

A

Increase in the copy number of genes

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9
Q

Gene mutation part of acquired resistance?

A

Mutation in genes that can occur to result in diff protein products–> microbes can use them

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10
Q

Horizontal gene transfer part of acquired resistance?

A

Genes can be passed from bacterial cell to bacterial cell (that arent parent and offspring)

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11
Q

Tranduction part of HGT?

A

Phages can infect bacteria and insert their genetic material into the bacteria’s genome

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11
Q

Transformation part of HGT?

A

one bacteria dies and its DNA is taken up by a nearby cell

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12
Q

Conjugation part of HGT?

A

Two bacteria near to each other create a bridge and genetic material is transferred

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13
Q

Intrinsic antibiotic resistance?

A

Efflux pumps, inactivating enzymes, decreased uptake, target alterations

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14
Q

Acquired antibiotic resistance?

A

Transduction, conjugation, transformation

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15
Q

Mechanisms of antibiotic resistance?

A

Change the drug, degrade the drug, alter the target, export (efflux)

16
Q

How can bacteria change the drug?

A

Produce enzymes that modify the drug–> add side groups, phosphorylate

17
Q

How can bacteria degrade the drug?

A

ENzymes can break down the drug
e.g. becat lactamases degreade beta lactam ring

18
Q

How can bacteria change the target?

A

Can add groups to the target via enzymes, or the genes for the target can mutate its DNA sequence

19
Q

Different wys to pump antibiotic out?

A

Can either be broad or specific depending on the bacteria, the pump and the antibiotic

20
Q

Types of spontaneous mutation that would have an effect?

A

Frameshift, point

21
Q

Example of a point mutation in bacteria?

A

GyrA region of DNA gyrase has a quinolone resistance determinant region–> if a certain chain of AAs is present in it that bacteria is resistant to quinolones

22
Q

How are point mutations passed on?

A

Vertically, not via HGT

23
Q

Example of an acquisition of alternative genes or pathways?

A

D-Ala-D-Ala in the peptidoglycan is converted to D-Ala-D-Lac via mutations in multiple genes to prevent

24
How can acquisition of alternative genes or pathways occur?
HGT, mutations, gene duplication
25
Most common way of getting vancomycin resistance?
Mobile genetic elements transfer
26
Ways to inactivate/degrede a drug?
Hydrolysis of drug--> B lactamases work on penicillins, tetracyclines Inactivation by modification--> transfer of chemical groups to the antibiotic
27
How are aminoglycosides modified?
Due to environmental changes/changes in the cell itself side groups are added to the drug
28
Why do gram -ve bacteria have more resistance than gram +ve ones?
They have efflux pumps-
29
Three components of efflux pump in gram -ves?
Inner membrane, periplasm and outer membrane portions
30
How are efflux pumps powered?
Proton motive force which generates ATP
31
Reducing spread of antibiotic resistance?
Minimize unnecessary antibiotic use, follow taking instructions, clean high contact areas
32
Antibiotic discovery methods?
Bacteriophages, genome mining, antibacterial antibodies, microbiome altering agents, virulence inhibition
33
Main causes of lack of antibiotics?
Science--> easy to find targets have been found so only difficult ones left Economic--> development of antibiotics delivers low ROI
34
Example of a new antibiotic?
Augmentin, cefiderocol
35
What does augmentin contain?
Beta-lactam antibiotic and beta lactamase inhibitor
36
What is ceiderocol made up of?
Fusion of a cephalosporin antibiotic and a siderophore (catechol)
37
Benefit of Augmentin and cefiderocol?
Both can resist beta lactamases