LM 2.34: Antibiotic Resistance II Flashcards
what is homologous recombination?
where you have 2 segments of DNA that have close DNA sequences
what is RecA?
the enzyme that carries out homologous recombination in bacteria
needs to base pair with chromosomal DNA and this only happens if the sequences are really similar
sequences must be very similar for RecA to work
what are transposons?require similar
they can move to another spot within a given DNA molecule or between two DNA molecules
they cannot by themselves jump out of a cell and go into another cell - so it’s not the same as tranduction, conjugation, etc.
transposition does NOT require base pairing between the Tn and target DNA which is different from homologous recombination
how do transposons get around the RecA-homologous recombination barrier?
Tns cut the DNAs and join their ends together
what are insertion sequences?
the smallest transposons
the main part of an IS is a gene, most of which specifies transposase that carriers out the transposition
there are also inverted terminal repeats which the transposase recognizes and cuts at
so since there’s no resistance gene why do we care? they can form composite transposons! when you get a transposon that undergoes replicative transposition in a short distance, then the whole segment between the two ISs can be a transposable element
so the central region plus the two ISs on each side made up a long terminal repeat and maybe the sequence in the middle IS a resistance gene!
what’s a composite transposon?
two ISs with a normal DNA sequence in the middle
transposase will cut the whole thing out!
this whole sequence can jump to another DNA molecule in the cell!
the composite transposons are great at picking up new DNA and this helps spread resistance!
the same IS is on each end
what are noncomposite transposon?
not the same IS on each end
what is surrogate selection?
selection for ANY ONE of these resistance genes selects for the entire plasmid
what are two major reservoirs of resistance?
- factory farms
2. hospitals
how do farms act as a resistance reservoire?
antibiotics are used as feed additives – subtherapeutic doses that are used as growth stimulates….
there are also bactieral diseases effecting plants so plants also get sprayed with antibiotics = crop-dusting…
this promotes bacterial resistance
how do hospitals act as a resistance reservoire?
lots of sick people need antibiotic treatment
there’s also defensive medicine where people over-treat just to protect themselves
there’s also a high population density and staff is a vector for bacteria…
what is triclosan?
it’s in toothpaste, cloth, soap, etc. it’s literally everywhere
what’s the problem with triclosan?
promotes antibiotic resistance spread…
non-specific efflux pumps confer resistance to triclosan and other antibitoics in P. aeruginosa
so the same resistance genes that specify resistance to other antibitiobics also specify for triclosan which selects for Ab-resistance plasmids
we also used to think it was non-specific but that’s not true; it inhibits a specific enzyme which is the target of TB drug isoniazid which is not good….
it’s also getting into our bodies because it’s found everywhere!!
why does triclosan contribute to antibiotic resistance?
inhibits bacterial enoyl-acyl carrier protein reductases
what is a good biomarker for bacterial infections?
procalcitonin
