June 17, 2025 • 11 mins
Bacterial genomics is the focus of our deep dive today, especially how it plays a crucial role in tackling antimicrobial resistance. Ashrita R, a student at Detroit Country Day School, is the creator of Back to Bacteria, a puppet show that guides us through the fascinating world of bacteria and DNA. The episode features special guests, Pinky the Antibiotic and Helix the DNA segment, who share insights on how antibiotic resistance develops and spreads, as well as how genomics can help in understanding and combating these issues. They also discuss a groundbreaking study that utilized bacterial genomics to investigate treatment failures in Staphylococcus aureus infections, shedding light on the adaptive mutations that contribute to antibiotic resistance. By the end of the show, Ashrita hopes you gain a greater understanding of bacterial genomics and its potential to inform personalized medicine, helping to ensure better outcomes in the fight against bacterial infections.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:11):
Hello, everyone, and welcometo the opening night of Bax Bacteria,
episode one, the Microbial Menace.
Your favorite fine theaterproduction starring your favorite
microbe.
Many of you have met me before.
Scratch that.
All of you have, because I'mright here in your gut.
But you probably first learnedmy name in your freshman biology
textbook.
Yes, that is I, the bacterialicon Escherichia coli.
(00:34):
But for my dearest listeners,call me Rick.
Our topic of the day isbacterial genomics, the study of
bacterial DNA, specificallyhow it can be used to combat antimicrobial
resistance.
We'll start things off with abrief introduction by our creator,
because for some reason, shewants to get emotional.
And then we'll launch into the learning.
Hi, everyone.
(00:54):
Thank you for making it to thefirst showing about bacteria.
Originally, I wanted to makean Omix puppet show for the end of
the year, Biofinal, as a joke.
After all, why would I risksuch a large part of my grade on
something that seems so silly?
But then I realized it was achance to combine some of my greatest
interests.
Genomics, arts and crafts, andmaking strange voices.
(01:16):
I began gaining an interest in genomics.
When I decided to try outVermeer Computational Biology Camp
the summer before ninth grade.
I didn't realize I haddiscovered one of my favorite fields
of study.
I continued to explore omicsthrough my school's guidance club
and the Mercor volunteerprogram, where I learned that by
analyzing gene expressionlevels in disease versus control
(01:38):
groups, scientists couldpinpoint what proteins were being
differentially expressed,leading them to find potential biological
processes associated with the condition.
This year in AP Bio, we learnabout microbial resistance and its
disastrous toll on humanlives, as well as the heavy financial
burdens.
I wanted to see if omics couldbe applied not only to humans, but
(01:59):
also to bacterial DNA to seewhat cellular pathways are involved
in antibiotic resistance andwhat potential solutions there are
to inhibit these pathways toincrease the capabilities of antibiotics.
Thank you, and I hope youenjoy the program.
Okay, enough of that.
Onto our first segment.
(02:19):
Our first guest specialist ishere to talk about antimicrobial
resistance.
Give a warm welcome to Pinkythe Antibiotica.
Hi, everyone.
My name is Pinky, and for aslong as I can remember, I've been
helping humans fight againstnasty bacterial infections.
In the beginning, I found thelife of an antibiotic fairly straightforward.
(02:40):
After all, killing bacteriaseems so easy.
But lately, me and countlessother antibiotic pills have been
struggling as bacteria mutateto resist our attacks.
This phenomenon is calledantibiotic resistance.
It's a serious global healththreat leading to 1.7 trillion in
economic losses annually, andit's expected to cause approximately
(03:01):
1.9 million deaths per year by 2050.
One thing that makes theproblem even worse is when humans
misuse antibiotic treatment,it leads to a higher rate of mutations.
When a bacterium developsantibiotic resistance, it spreads
rapidly across the environment.
This is because resistantbacteria can divide so quickly to
(03:24):
create more resistant bacteria.
Additionally, bacteria canrelease plasmids with resistant genes
so that previously nonresistant bacteria become resistant.
Eventually, there can bemillions of bacteria that antibiotics
can do nothing against.
However, pathogen genomics canhelp us understand how antimicrobial
(03:46):
resistance starts and spreads.
By tracking resistance acrosshumans, animals and the environment,
scientists can use genomics todiscover new resistance mechanisms.
And if we find pathways, wecan also figure out how to block
them.
There are many types ofgenomic measures, but here are some
major ones.
There's next generationsequencing, which is the fastest
(04:08):
and most affordable genomesequencing invented in the early
2000s.
Additionally, there's wholegenome sequencing, a subset of next
gen sequencing where, as thename suggests, you sequence the animal's
entire genome.
Additionally, many types ofgenomics focus on different pathogens,
such as bacterial genomics,which focuses on bacterial genomes,
(04:29):
and cancer genomics, whichfocuses on studying cancer cells,
specifically towardsantimicrobial resistance, or amr.
These techniques are used toidentify resistant genes and develop
better ways to control infections.
That sounds like a world of possibilities.
Now welcome our next guestwho's certainly a gene ES and will
(04:49):
be taking us deeper into theworld of bacterial genomics.
Thank you.
Welcome Helix, from what Iunderstand, you're a piece of sequence
DNA.
Yes sir.
Why don't you give us a bit ofhistory on bacterial DNA sequencing?
Well, the first bacterialgenome to be sequenced was hemophilus
influenza in 1996.
(05:10):
It paved the way forscientists to understand bacterial
physiology, metabolism and virulence.
It's always influenza.
Then in 1997, E.
Coli was sequenced and in theearly 2000s next generation sequencing
was developed and many morebacteria were able to be used to
(05:31):
investigate amr.
For example, mendhicillinresistant Staphylococcus aureus genomes
were sequenced in 2001 tobetter understand the mechanisms
of drug resistance.
Early whole genome sequencingstudies also uncovered the role of
mobile genetic elements suchsuch as plasmids and transposons,
(05:51):
which are pieces of DNA thatspread resistance through bacterial
populations.
Statistical genomic methodsusing large data sets of bacterial
DNA sequences were also usedto identify resistance associated
mutations such as the walk Rmutation which is associated with
vaxomycin resistance in S.
(06:13):
Aurease bacteria.
But what exactly are the goalsof bacterial genomics?
How can this stuff help combatbacterial illness?
Well, the most direct goal isto find resistance genes or mutations
in bacteria.
But scientists can also usethese genes, as well as their expression
(06:34):
levels, to predict howresistant a strain of bacteria will
be towards an antibiotic.
Scientists are also learningmore about how resistance evolves
over time, as well as how itspreads so quickly, even between
different people and environments.
Well, what tools do they useto do this?
Well, AI and machine learninghave been commonly used to analyze
(06:56):
large scale data sets, andCRISPR gene editing can be used to
validate conclusions bytesting to see if genes hypothesized
to cause resistance actuallydo in a lab setting.
Moreover, genetics can be usedto show how resistant bacteria move
between different groups,whether it be from country to country
or even animals to humans.
Moreover, phylogenetic treescan be developed using similarities
(07:19):
between DNA sequences to trackhow bacteria evolve from each other
and how resistance evolvesover time.
Well, what are some future applications?
Some of the most excitingapplications of genomics in a clinical
setting is precision medicineand an approach to healthcare that
takes differences in otherpeople's genes into account to increase
(07:40):
the effectiveness of medication.
Scientists are working ondeveloping genomic based diagnostic
tests that can accuratelydetect resistance mechanisms in clinical
samples using the sequencingof bacteria infected the samples
or sequences from clinicalsamples, and can be used to predict
resistance determinants.
(08:01):
These rapid diagnostictechniques can potentially guide
physicians in making informedtreatment decisions and optimizing
antibiotic therapy to reducethe risk of treatment failure.
Okay, now that ourintroduction and background sections
are over, we enter to the realreason we're here.
Well, isn't that because of abio final?
(08:23):
Well, partly, but it's also totalk about a groundbreaking scientific
study that was published inNature just this week.
In the last year, there havebeen many breakthroughs using genomic
data in clinical settings, andPinky Helix and I are about to share
one more.
For the first time, scientistshave used bacterial genomics to investigate
treatment failure andStaphylococcus aureus infections.
(08:46):
Inspired by strategies used incancer genomics, scientists applied
combinations of bacterialgenomics and antibiotic susceptibility
testing to identify and trackadaptive mutations that cause antibiotics
to fail.
But why is this work sosignificant anyways?
Well, this study is especiallynoteworthy considering how novel
(09:09):
bacterial genomics is comparedto human and cancer DNA sequencing
studies in cancer, detectingspecific mutations can allow doctors
to make informed andindividual decisions with better
outcomes.
Similarly, the detection ofadaptive mutations especially in
response to antibiotics, canhelp us understand why antibiotic
(09:31):
failure occurs and can help usmake predictions about amr.
Really?
How?
Well, take the example ofStaphylococcus aureus, which often
gains resistance to B.
Lactam antibiotics such asoxalisate due to the presence of
modified penicillin binding proteins.
However, oxalicillinresistance even occurs in the absence
(09:53):
of this protein.
By assessing bacterial genomicdata, scientists saw the acquisition
of multiple adaptivemutations, such as the development
of the TAG O gene that drovepenicillin resistance.
This has potential clinicalimplications, since genes such as
TAG O can act as biomarkers tohelp identify treatment failure early,
(10:14):
and it can inform potentialtreatment alternatives.
And it's just not Staphylococcus.
Similar studies can be donewith tuberculosis, pneumonia and
many others, even E.
Coli.
Because I have a few peskyneighbors that I just can't seem
to get rid of.
Well, sure, I guess.
On that happy note, we havereached the end of our segment.
(10:37):
Give a special thanks to ourguest speakers, Pinky the Antibiotic
and Helix the DNA segment.
And that's it for today folks.
Here on Episode one, theMicrobial Menace, we've learned about
bacterial genomics, the studyof bacterial DNA sequences, specifically
how it can be applied to solveproblems caused by antimicrobial
(10:57):
resistance.
We took a deep dive into aspecific research study involving
Staphylococcus aureusbacteria, and learned about the applications
of bacterial genomics andpersonalized precision medicine from
all of us here at Back to Bacteria.
We thank you for listening andhope you either learned something
or were at least mildly amused.
We'll see you next time forEpisode two, Attack of the Coli.
Hello, everyone, and welcometo the opening night of Bax Bacteria,
episode one, the Microbial Menace.
Your favorite fine theaterproduction starring your favorite
microbe.
Many of you have met me before.
Scratch that.
All of you have, because I'mright here in your gut.
But you probably first learnedmy name in your freshman biology
textbook.
Yes, that is I, the bacterialicon Escherichia coli.
(00:34):
But for my dearest listeners,call me Rick.
Our topic of the day isbacterial genomics, the study of
bacterial DNA, specificallyhow it can be used to combat antimicrobial
resistance.
We'll start things off with abrief introduction by our creator,
because for some reason, shewants to get emotional.
And then we'll launch into the learning.
Hi, everyone.
(00:54):
Thank you for making it to thefirst showing about bacteria.
Originally, I wanted to makean Omix puppet show for the end of
the year, Biofinal, as a joke.
After all, why would I risksuch a large part of my grade on
something that seems so silly?
But then I realized it was achance to combine some of my greatest
interests.
Genomics, arts and crafts, andmaking strange voices.
(01:16):
I began gaining an interest in genomics.
When I decided to try outVermeer Computational Biology Camp
the summer before ninth grade.
I didn't realize I haddiscovered one of my favorite fields
of study.
I continued to explore omicsthrough my school's guidance club
and the Mercor volunteerprogram, where I learned that by
analyzing gene expressionlevels in disease versus control
(01:38):
groups, scientists couldpinpoint what proteins were being
differentially expressed,leading them to find potential biological
processes associated with the condition.
This year in AP Bio, we learnabout microbial resistance and its
disastrous toll on humanlives, as well as the heavy financial
burdens.
I wanted to see if omics couldbe applied not only to humans, but
(01:59):
also to bacterial DNA to seewhat cellular pathways are involved
in antibiotic resistance andwhat potential solutions there are
to inhibit these pathways toincrease the capabilities of antibiotics.
Thank you, and I hope youenjoy the program.
Okay, enough of that.
Onto our first segment.
(02:19):
Our first guest specialist ishere to talk about antimicrobial
resistance.
Give a warm welcome to Pinkythe Antibiotica.
Hi, everyone.
My name is Pinky, and for aslong as I can remember, I've been
helping humans fight againstnasty bacterial infections.
In the beginning, I found thelife of an antibiotic fairly straightforward.
(02:40):
After all, killing bacteriaseems so easy.
But lately, me and countlessother antibiotic pills have been
struggling as bacteria mutateto resist our attacks.
This phenomenon is calledantibiotic resistance.
It's a serious global healththreat leading to 1.7 trillion in
economic losses annually, andit's expected to cause approximately
(03:01):
1.9 million deaths per year by 2050.
One thing that makes theproblem even worse is when humans
misuse antibiotic treatment,it leads to a higher rate of mutations.
When a bacterium developsantibiotic resistance, it spreads
rapidly across the environment.
This is because resistantbacteria can divide so quickly to
(03:24):
create more resistant bacteria.
Additionally, bacteria canrelease plasmids with resistant genes
so that previously nonresistant bacteria become resistant.
Eventually, there can bemillions of bacteria that antibiotics
can do nothing against.
However, pathogen genomics canhelp us understand how antimicrobial
(03:46):
resistance starts and spreads.
By tracking resistance acrosshumans, animals and the environment,
scientists can use genomics todiscover new resistance mechanisms.
And if we find pathways, wecan also figure out how to block
them.
There are many types ofgenomic measures, but here are some
major ones.
There's next generationsequencing, which is the fastest
(04:08):
and most affordable genomesequencing invented in the early
2000s.
Additionally, there's wholegenome sequencing, a subset of next
gen sequencing where, as thename suggests, you sequence the animal's
entire genome.
Additionally, many types ofgenomics focus on different pathogens,
such as bacterial genomics,which focuses on bacterial genomes,
(04:29):
and cancer genomics, whichfocuses on studying cancer cells,
specifically towardsantimicrobial resistance, or amr.
These techniques are used toidentify resistant genes and develop
better ways to control infections.
That sounds like a world of possibilities.
Now welcome our next guestwho's certainly a gene ES and will
(04:49):
be taking us deeper into theworld of bacterial genomics.
Thank you.
Welcome Helix, from what Iunderstand, you're a piece of sequence
DNA.
Yes sir.
Why don't you give us a bit ofhistory on bacterial DNA sequencing?
Well, the first bacterialgenome to be sequenced was hemophilus
influenza in 1996.
(05:10):
It paved the way forscientists to understand bacterial
physiology, metabolism and virulence.
It's always influenza.
Then in 1997, E.
Coli was sequenced and in theearly 2000s next generation sequencing
was developed and many morebacteria were able to be used to
(05:31):
investigate amr.
For example, mendhicillinresistant Staphylococcus aureus genomes
were sequenced in 2001 tobetter understand the mechanisms
of drug resistance.
Early whole genome sequencingstudies also uncovered the role of
mobile genetic elements suchsuch as plasmids and transposons,
(05:51):
which are pieces of DNA thatspread resistance through bacterial
populations.
Statistical genomic methodsusing large data sets of bacterial
DNA sequences were also usedto identify resistance associated
mutations such as the walk Rmutation which is associated with
vaxomycin resistance in S.
(06:13):
Aurease bacteria.
But what exactly are the goalsof bacterial genomics?
How can this stuff help combatbacterial illness?
Well, the most direct goal isto find resistance genes or mutations
in bacteria.
But scientists can also usethese genes, as well as their expression
(06:34):
levels, to predict howresistant a strain of bacteria will
be towards an antibiotic.
Scientists are also learningmore about how resistance evolves
over time, as well as how itspreads so quickly, even between
different people and environments.
Well, what tools do they useto do this?
Well, AI and machine learninghave been commonly used to analyze
(06:56):
large scale data sets, andCRISPR gene editing can be used to
validate conclusions bytesting to see if genes hypothesized
to cause resistance actuallydo in a lab setting.
Moreover, genetics can be usedto show how resistant bacteria move
between different groups,whether it be from country to country
or even animals to humans.
Moreover, phylogenetic treescan be developed using similarities
(07:19):
between DNA sequences to trackhow bacteria evolve from each other
and how resistance evolvesover time.
Well, what are some future applications?
Some of the most excitingapplications of genomics in a clinical
setting is precision medicineand an approach to healthcare that
takes differences in otherpeople's genes into account to increase
(07:40):
the effectiveness of medication.
Scientists are working ondeveloping genomic based diagnostic
tests that can accuratelydetect resistance mechanisms in clinical
samples using the sequencingof bacteria infected the samples
or sequences from clinicalsamples, and can be used to predict
resistance determinants.
(08:01):
These rapid diagnostictechniques can potentially guide
physicians in making informedtreatment decisions and optimizing
antibiotic therapy to reducethe risk of treatment failure.
Okay, now that ourintroduction and background sections
are over, we enter to the realreason we're here.
Well, isn't that because of abio final?
(08:23):
Well, partly, but it's also totalk about a groundbreaking scientific
study that was published inNature just this week.
In the last year, there havebeen many breakthroughs using genomic
data in clinical settings, andPinky Helix and I are about to share
one more.
For the first time, scientistshave used bacterial genomics to investigate
treatment failure andStaphylococcus aureus infections.
(08:46):
Inspired by strategies used incancer genomics, scientists applied
combinations of bacterialgenomics and antibiotic susceptibility
testing to identify and trackadaptive mutations that cause antibiotics
to fail.
But why is this work sosignificant anyways?
Well, this study is especiallynoteworthy considering how novel
(09:09):
bacterial genomics is comparedto human and cancer DNA sequencing
studies in cancer, detectingspecific mutations can allow doctors
to make informed andindividual decisions with better
outcomes.
Similarly, the detection ofadaptive mutations especially in
response to antibiotics, canhelp us understand why antibiotic
(09:31):
failure occurs and can help usmake predictions about amr.
Really?
How?
Well, take the example ofStaphylococcus aureus, which often
gains resistance to B.
Lactam antibiotics such asoxalisate due to the presence of
modified penicillin binding proteins.
However, oxalicillinresistance even occurs in the absence
(09:53):
of this protein.
By assessing bacterial genomicdata, scientists saw the acquisition
of multiple adaptivemutations, such as the development
of the TAG O gene that drovepenicillin resistance.
This has potential clinicalimplications, since genes such as
TAG O can act as biomarkers tohelp identify treatment failure early,
(10:14):
and it can inform potentialtreatment alternatives.
And it's just not Staphylococcus.
Similar studies can be donewith tuberculosis, pneumonia and
many others, even E.
Coli.
Because I have a few peskyneighbors that I just can't seem
to get rid of.
Well, sure, I guess.
On that happy note, we havereached the end of our segment.
(10:37):
Give a special thanks to ourguest speakers, Pinky the Antibiotic
and Helix the DNA segment.
And that's it for today folks.
Here on Episode one, theMicrobial Menace, we've learned about
bacterial genomics, the studyof bacterial DNA sequences, specifically
how it can be applied to solveproblems caused by antimicrobial
(10:57):
resistance.
We took a deep dive into aspecific research study involving
Staphylococcus aureusbacteria, and learned about the applications
of bacterial genomics andpersonalized precision medicine from
all of us here at Back to Bacteria.
We thank you for listening andhope you either learned something
or were at least mildly amused.
We'll see you next time forEpisode two, Attack of the Coli.
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