Why is it that people die due to antimicrobial resistance? (NO)
-microbes have learned how to take antibiotics and convert them into more long lasting metabolites to support their growth and persistence
-the selective pressure created by antibiotics, allows for resistant bacteria to thrive (natural selection, horizontal gene transfer, etc)
how can we think of the human host, microorganisms, and antimicrobial agents? (NO)
-think of them like a triangle, where any alteration to one point affects the other 2
what effect does an increasing population have on antimicrobial resistance? (NO)
-it increases it
-more use of antibiotics which leads to more development of resistant bacteria
-more spread between people which spreads the resistant bacteria
Where is antibiotic use currently sitting? where is it set to go? (NO)
-currently 70 billion standard units/year for human use with an expected increase of 30% by 2030
-63,151 +/- 1,560 tons/year for livestock with an expected increase of 67% by 2030
how has antimicrobial resistance evolved? (NO)
-AMR has always been around but it is at an exponentially higher rate now
-this is due to the increasing use of antibiotics
-S. aureus has seen a lot of evolution from the 1950s to the early 2000s
-penicillin, methicillin, and vancomycin resistant S. aureus have arose over the years, with the time between the introduction of an antibiotic and the development of its resitant strain getting smaller and smaller.
what is a mechanism that bacteria use in order to develop resistance faster? (NO)
-quorum sensing to transfer resistance plasmids (enhances efficiency of conjugation)
what causes genetic change within bacteria? (NO)
-mutation
-horizontal gene transfer
what is mutation? (NO)
-a change in the nucleotide sequence of DNA
-may cause a change in a protein encoded by a gene (new function or no function)
-also called vertical gene transfer if passed onto progeny (if the mutation is stable and persists)
what is horizontal gene transfer? (NO)
-genetic information being passed from one living cell to another cell of the same generation
-conjugation, transformation, transduction
-if the addition of new information is stable, it can be passed onto progeny
what helps bacteria overcome harmful mutations? (NO)
-quorum sensing through autoinducers
- IA-2 and AHL-2 in gram negative
- AIP-2 in gram positive
what are the two different types of possible mutations? (NO)
-base substitution (point mutation)
-frameshift mutation
what is required for a bacteria to keep a plasmid as a stable genetic element? (NO)
-selective pressure
-if there is no selective pressure, the plasmid eventually dilutes out of the population to not waste energy
what is a base substitution mutation? (NO)
-a single nucleotide is replaced by another nucleotide
-when DNA replicates it results in a substituted base pair
-can be considered a missense mutation if the change in nucleotide results in a change in amino acid
what is a frameshift mutation? (NO)
-can be an insertion or deletion of one or two nucleotides that changes the reading frame of the mRNA
-this means that the sequence of amino acids is changed downstream of a mutation site
-almost always results in a non-functional protein
-can result in a early stop codon (UAA, UGA, UAG)
what are the two ways mutations can occur? (NO)
-spontaneously
-induced
what is a spontaneous mutation? (NO)
-a mutation that occurs in the absence of mutagens due to the occasional mistakes during DNA replication
what is an induced mutation? (NO)
-a mutation that occurs when DNA damaging agents (mutagens) cause changes in the DNA sequence
-ex: radiation, UV exposure, chemicals (ethidium bromide, gel red)
what are the possible results of a mutation in terms of proteins? (NO)
-no effect on the protein (remains functional) = silent mutation
-a protein with a different amino acid sequence that may have an altered function = missense mutation
-an incomplete (truncated) protein due to a premature stop codon that usually becomes non-functional = nonsense mutation
what is transfection? (NO)
-an artificial method to infect cells with a virus
what is transformation? (NO)
-a method of horizontal gene transfer where a fragment of DNA is acquired by a bacteria
-homologous recombination occurs and the DNAa fragment becomes integrated into the bacterial chromosome so that it can be replicated and passed on to daughter cells
what is conjugation? (NO)
-transfer of a plasmid through a sex pilus between bacteria in the same generation (not between progeny)
what is transduction? (NO)
-phage-mediated transfer of genetic material
-lysogenic phage injects its genetic material into the material for it to become integrated through homologous recombination
-the genetic material passed allows for phages to be formed so that there is more transfer of genetic material (can be phage DNA (specialized) or regular DNA (generalized))
how can integrons mediate resistance? (NO)
-resistance cassettes can be taken up into the integron
-in many cases multiple can be taken up to create a wider range of resistance
-they can be in the chromosome or the plasmid, or they can be placed into transposons and then be spread further
what is the difference between transposons and integrons? (NO)
-integrons are present in a plasmid (type 1-3) or in chromosomes (type 4 and on) they are often more stable and they code for an integrase
-transposons are present in all free living bacteria, primarily in the chromosome but in plasmids as well, and they code for transposase