Antimicrobial resistance mechanisms Flashcards
Define susceptibility
Organism is inhibited by the usually achievable concentrations of antimicrobial agent when the dosage recommended to treat at site of infection is used
Define susceptible dose dependent
Susceptibility depends on the dosage regimen used - to achieve levels that are clinically effective, there must be greater antimicrobial exposure than achieved with the dose used to determine the breakpoints
Define “intermediate” resistance
Response rates/zone size/MICs are lower than for susceptible isolates
Define resistance
Organism is not inhibited by the usually achievable concentrations of the agent with normal dosage schedules or fall into the range in which a specific known resistance mechanism is likely
Define MDR
Acquired non-susceptibility to ≥ 1 agent in ≥3 antimicrobial categories
Define XDR
Acquired non-susceptibility ≥ 1 agent in all but 2 or less antimicrobial categories
Name mechanisms of genetic variability of bacteria
Intracellular
Intercellular
What intracellular mechanisms can result in genetic variability of bacteria?
Homologous recombination
Mutations
What intercellular mechanisms can result in genetic variability in bacteria?
Bacterial
- transformation
- transduction
- transposition
- conjugation
Explain bacterial transformation
Bacterial lysis -> uptake of free segments of naked bacterial DNA from surroundings through the cell membrane -> combination of new DNA with pre-existing DNA -> degradation of unused DNA -> expression of new genes
Give examples of bacteria that often undergo transformation
Neisseria
Haemophilus influenza B
Strep pneumo
Which enzyme prevents bacterial transformation and how does it do this?
Deoxyribonucleases as they break down free DNA
Explain bacterial conjugation
Transfer of plasmids by a bridge like connection between two bacteria
Example: F+ bacteria connect with F- bacteria via the sex pills -> a single strand of plasmid DNA is transferred from F+ bacteria to F- bacteria -> 2 F+ bacteria
What is F factor?
Fertility factor - a bacterial plasmid that enables transfer of genetic material between bacteria
What are Hfr cells?
High frequency recombination cells - bacteria with a conjugative plasmid integrated into their chromosomal DNA
Explain bacterial transduction
The process of gene transfer between bacteria via bacteriophages
What is the difference between a prophage and a lytic phage?
Lytic phage - bacteria is destroyed
Prophage - bacteria integrates the phage DNA into its genome
Differentiate generalised vs specialised transduction
Generalised - any portion of the bacterial genome is transferred
Specialized - a specific portion of the bacterial genome is transferred
Explain generalised transduction
Bacteriophage attaches itself to the bacterial cell wall and injects its DNA into the bacterium -> cleavage of bacterial DNA and replication of viral DNA -> formation of new bacteriophages with phage capsids containing fragments of bacterial DNA -> lysis of bacterium -> release of new bacteriophages
Explain specialised transduction
Bacteriophage infects bacteria -> viral DNA incorporated into bacterial DNA at specific location but remains inactive -> when activated the viral DNA is replicated -> viral DNA and flanking bacterial DNA excised from the bacterial genome -> excised DNA is incorporated into new bacteriophage capsids -> lysis of bacterium -> release of new bacteriophages
Give examples of toxins that have their genes transferred via specialised transduction
Erythrogenic
Cholera
Diphtheria
Shiga
Botulinum
Explain bacterial transposition
Exchange of genetic information via transposons within the genome or between genomes of various bacteria
Define beta lactamases
Enzymes that inactivate beta lactam antibiotics by splitting the amide bond of the beta lactam ring
What gene encodes for beta lactamases?
Bla genes
