ID Lecture 4: Intro to Antimicrobial Agents and Antimicrobial Resistance | Quizlet

Beta-lactams MOA

bind in the site of PBP to prevent crosslinking of peptidoglycan (cell wall synthesis inhibitors)

Quinolones MOA

inhibits DNA topoisomerase to prevent DNA replication (DNA replication inhibitors)

Tetracyclines MOA

prevents bacterial protein synthesis by inhibiting the 30S subunit (protein synthesis inhibitor)

Macrolides MOA

prevents bacterial protein synthesis by inhibiting the 50S subunit (protein synthesis inhibitor)

Bacteria can develop antibiotic resistance through what major mechanisms?

1. Limit intake

2. Active export

3. Inactivation or modification of the drug

4. Alteration of antibiotic targets

5. Target bypass

Intrinsic resistance

organism is inherently not susceptible to the antibiotic due to factors like the antibiotic size, characteristics, biofilm production, etc.

How do gram-positive bacteria gain intrinsic resistance?

they have a thick, heavy crosslinked, and hydrophilic peptidoglycan cell wall

How do gram negative bacteria gain intrinsic resistance?

they have an outer membrane with porin channels that allow for entry of hydrophilic molecules - preventing LARGE molecules from entering

Which antibiotic molecules are good for gram negative bacteria?

small hydrophilic molecules

Which antibiotic molecules are good for gram positive bacteria?

small and large molecules

How do bacteria limit intake of antibiotics?

reduced membrane permeability and decrease number of porin channels

Active export mechanism of resistance

enhanced export by energy-dependent efflux pumps

Inactivation or modification of the drug

enzymes that destroy or modify the antibiotic

Alteration of antibiotic targets

amino acid substitutions or post-translational modifications prevent the antibiotic from binding to its target

Target bypass

bacteria develop alternate pathways or overproduce the target so that it takes more of the antibiotic

Can bacteria have multiple mechanisms of resistance?

Yes

How is antimicrobial resistance acquired?

Mutations to genomic DNA

Horizontal gene transfer

What are the different types of horizontal gene transfer?

Transformation

Conjugation

Transduction

How do point mutations cause antibiotic resistance?

single mutations increase resistance by a little - but they add up if a bacteria has multiple mutations

What is required for horizontal gene transfer?

mobile genetic elements (MGE)

What are mobile genetic elements?

genetic material that can move around within a genome or that can be transferred between species

Ex: plasmid, transposon, gene cassette, or phage

Transformation

dead bacteria that release their genetic elements into the environment so that living cells can uptake it

What do bacteria need in order to uptake genetic elements from the environment?

competence

Conjugation

MGE's get transferred through a pilus from the donor cell to the recipient cell

Transduction

virus transfers genetic material from one bacterium to another

What are the mobile genetic elements?

Plasmids

Gene cassettes

Transposons

Phages

Minimum inhibitory concentration (MIC)

the lowest concentration of antimicrobial that inhibits growth of bacteria in vitro

Zone diameter (ZD)

the diameter of bacterial killing around an antibiotic infused disk

Breakpoints

determed by the FDA and CLSI to know if the MIC or ZD is sufficient for clinical use

Can susceptibility breakpoints change?

yes - especially as resistance increases

MIC > breakpoint

resistant

MIC < breakpoint

susceptible

MIC = Breakpoint

Intermediate