Exam 1: Antimicrobial Resistance Flashcards by Anika Eidson

What is minimum inhibitory concentration?

The lowest concentration of a drug that will completely inhibit growth of a bacterial strain

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When is a bacterial strain resistance to an antibiotic?

When its MIC is higher than the normally achievable and tolerated concentration of the drug attained in tissues with maximum dosage

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How do antibiotics act?

By inactivating a specific bacterial target

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What are mechanisms of antibiotic resistance?

Modification of the antibiotic target
Enzymatic inactivation of the antibiotic
Impermeability
Active efflux

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What do beta-lactams (penicillins and cephalosporins) do?

Alteration of the target protein (penicillin-binding protein) so that the antibiotic no longer binds it

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What are penicillin-binding proteins?

Bacterial enzymes that mediate crosslinking of peptidoglycan in formation of the cell wall

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What is the modification of the target antibiotic resistance a common mechanism of?

Causing gram-positive bacterial beta-lactam resistance

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What is an example of enzymatic inactivation of the antibiotic?

Beta-lactamase

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What are beta-lactamases?

Bacterial enzyme that cleaves the beta-lactam ring

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Where is beta-lactamase secreted by gram-negative?

Periplasmic space

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Where is beta-lactamase secreted by gram-positive?

Into extracellular fluid

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What are beta-lactamases usually active against?

A subset of beta-lactam antibodies

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What can beta-lactamase inhibitors (clavulanic acid) do?

Prevent inactivation by beta-lactamases

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What does the gram-negative outer membrane do in impermeability?

Limits antibiotic access to the cytoplasmic membrane because antibiotics must first diffuse through pores in outer membrane

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What is impermeability thought to be the reason for?

E. coli innate resistance to macrolides

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What do mutations in porins do to impermeability?

Limit diffusion of antibiotics

A single porin mutation can confer resistance to more than one antibiotic type

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What is an example of active efflux?

Tetracycline

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What is tetracycline?

Bacterial cytoplasmic membrane proteins that catalyze energy-dependent transport of tetracycline out of the cytoplasm

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What does active efflux do?

Prevents sufficient antibiotic concentrations in the cytoplasm to inhibit protein synthesis

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What does the active efflux system also exist for?

Quinolones

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How does antibiotic resistance arise?

Genetic mechanisms
Phenotypic variants
Biofilms

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What are the genetic mechanisms of antibiotic resistance?

Genetic resistance is likely to be detected by susceptibility testing; therefore, it is usually detected at the onset of therapy
Unlikely to appear during a course of antibiotic therapy

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What are the 2 mechanisms that genetic resistance can arise?

Gaining the ability to resist one or more antibiotics by acquisition of genes
Resistance from random mutations

What are antibiotic resistance genes usually acquired on?

Plasmids

What do almost all antibacterial drugs have?

A corresponding resistance gene on at least one type of R plasmid

What do resistance (R) plasmids do?

Mediate resistance to more than one antibiotic

What can plasmids carry?

Transposons

What does gene acquisition typically result in?

Rapid acquisition of high-level resistance

What enzymatic antibiotic inactivation and active efflux require for the function to acquired?

The acquisition of a gene

What can the altered antibiotic target strategy occur by?

Acquisition of a gene encoding an altered target

What type of mutation are the random mutations typically?

Point mutations (change of one base pair into another)

What can random mutations do?

Revert back to the original gene sequence

What can a single base pair change result in?

High level resistance, but often multiple mutations have to be acquired so development of resistance can be gradual

How can random mutations result in resistance?

By either reducing permeability or altering target affinity

What can random mutations do in addition to causing antibiotic resistance?

They can be deleterious and cause some degree of growth impairment, and in some cases cause reduction in virulence (fitness cost)

What is fitness cost?

Often the mutation causing resistance also has a cost due to decreased function of the altered target

What do random mutations carry more than horizontal gene transfer?

Fitness cost

What mechanisms of antibiotic resistance does gene acquisition act by?

Alteration of target Inactivation of antibiotic Active efflux

What mechanisms of antibiotic resistance does random mutation act by?

Alteration of target | Impermeability

Why can phenotypic variants not be detected on antibiotic sensitivity testing?

It is not genetic

What are the types of phenotypic variants?

Bacterial persisters Small colony variants L-forms

What are bacterial persisters?

Non- or slow-growing reversible phenotypic variants of the wild type, tolerant to bactericidal antibiotics

What is persister tolerance of antibiotics due to?

Inhibition of essential cell functions during antibiotic stress, resulting in inactivity of the antibiotic target

What does persistence require?

Coordinated metabolic changes

What is entry and exit from the persister state regulated by?

Signal molecules

What do small colony variants have?

Reduced electron transport, which leads to decreased ATP syntheesis

What is the cause of reduced electron transport in small colony variants?

Reduced hemin or menadione biosynthesis or defective thymine deficiency

What is the result of reduced electron transport in small colony variants?

Decreased metabolism and decreased uptake of antibiotic, causing temporary antibiotic resistance

When do L-forms occur?

When bacteria lose their cell wall | They are temporarily more resistance to beta-lactam antibiotics

Where are L-forms found?

Historically in gram-negative, but recently found in listeria and mycobacterium

When do L-forms work?

When bacteria are in an environment where they are not susceptible to osmotic lysis

What is biofilm?

A structure community of bacteria enclosed in a self-produced polymeric matrix and adherent to an inert or living surface

What can bacteria in a biofilm do?

Convert into a regular planktonic state

What is resistance due to in biofilm?

Slower growth rates of bacteria within biofilms Decreased diffusion of antibiotics through the biofilm Accumulation of enzymes that contribute to resistance Activation of stress response in bacteria in biofilms

Where can biofilms be found?

Indwelling catheters