Topic 7B Antimicrobial Resistance (mechanism for acquired resistance) Flashcards
What is chromosomal mutation
one or more single nucleotide polymorphisms (SNPs) in a gene located on the chromosome.
Spontaneous mutations of DNA polymerase occur in 1 in 1,000,000 to 1 in 100,000,000 synthesized bases. The DNA
repair polymerases have a higher error rate than the DNA replication polymerases.
Induced mutations are caused by radiation or mutagens (chemicals which interact with DNA).
What is mis-incorporation mutation
incorrect base-pairing. Mutagens causing this are alkylating agents or base analogs.
What is frame shift mutation
“InDels” (insertions or deletions). Mutagens causing this are intercalating agents.
What is acquired resistance from mutation
If the gene for the drug target is mutated, it may be less likely to interact with antibiotics.
If genes encoding drug uptake are mutated, it may limit the drug’s ability to enter the cell.
• Example: a decreased rate of porin biosynthesis.
Genetic elements which control gene expression can also be mutated.
• Increased expression of efflux pumps will increase export of the drug.
• Increased expression of precursor biosynthesis will overcome competitive inhibitors, such as sulfonamid
What is mobile genetic elements
- transfer complete pieces of genetic information from a donor to a recipient.
Once inside the recipient, the DNA must either possess its own origin of replication or integrate into the chromosome.
• Plasmids possess their own origin of replication (OriR).
• Transposons integrate into the chromosome via transposition.
• Transducing particles/phages integrate into the chromosome via recombina
What is plasmids
small double stranded DNA (dsDNA) molecules possessing their own origin of replication (OriR), allowing them to replicate independently of the cell.
Copy number effects resistance: 1-20 copies is considered low, 20 or more is considered high.
What is mobilizable plasmid
- some plasmids possess an origin of transfer (OriT), allowing them to transfer themselves
between bacteria.
F-Plasmids contain the transfer gene. R-Plasmids contain both the transfer gene and an antibiotic resistance gene. An F+ donor bacteria creates an F-pilus to a F‒ recipient bacteria and sends over a single strand of the plasmid.
What is transducing particle/phage
- sometimes a viral capsid may be packed with host DNA instead of the viral genome. The viral spike proteins ensure delivery of the host DNA (donor DNA) into the new recipient cell.
If integrated into the recipient chromosome, it becomes part of the genome and can be replica
What is generalized transduction
- more common method:
1) A bacteriophage (bacteria virus) attaches to a receptor on a host cell and injects its viral DNA.
2) Enzymes encoded by the phage break down the bacteria’s DNA.
3) During viral construction, some of the broken bacterial DNA enters a capsid, creating a transducing phage. 4) The transducing phage attaches to a receptor on another host cell and injects the stolen bacterial DNA.
5) The injected bacterial DNA integrates into the recipient chromosome, becoming part of the genome.
What is specialized transduction
less common method:
1) A bacteriophage (bacteria virus) attaches to a receptor on a host cell and injects its viral DNA.
2) The phage DNA integrates into the host cell chromosome to become a prophage.
3) When the virus is ready to leave, it cuts its DNA out of the chromosome, but may mistakenly leave some of its DNA
behind while taking some of the bacterial DNA with it, creating a defective phage.
4) The defective phage attaches to a receptor on another host cell and injects the stolen bacterial DNA.
5) The injected bacterial DNA integrates into the recipient chromosome, becoming part of the genome.
What is transposons
a self-mobilizing pieces of DNA.
A basic transposon contains an insertion sequence (IS), a transposase (cuts DNA at insertion sequence), and a
transposase repressor (turns off transcription of the transposase).
A composite/complex transposon also carries an antibiotic resistance gene.
Even without carrying an antibiotic resistance gene, if the transposon places itself into the chromosome in an area where it interrupts a gene required for the drug target, then it will confer resistance
What is combination of mobile genetic elements
- two or more MGEs may combine to confer resistance to a microbe.
Vancomycin-resistant staphylococcus aureus (VRSA) received its vancomycin resistance from vancomycin-resistant enterococcus faecalis (VRE).
• VRE contained a plasmid and that plasmid contained a transposon with the vancomycin resistance gene. Since staphylococcus aureus (SA) already contained a plasmid of its own, which was in the same “incompatibility group”, the SA plasmid should have destroyed the VRE plasmid when it was transferred over. However, since the resistance gene was on a transposon, it jumped from the VRE plasmid to the SA plasmid before it was destroyed, creating the VRSA strain.
What is antibiotic resistance genes
- usually occurs by altering a drug with an enzyme.
Beta-lactamases may defeat penicillins and cephalosporins. Clavulanate can be used to counter beta-lactamases. Carbapenems are immune to beta-lactamases, but may be defeated by carbapenemases.
Unfortunately, there are no good counters for carbapenemases.
