BIO 205 Chapter 7 Microbial Genetics

welcome to the narration for chapter 7 microbial genetics this chapter is very very similar in content with stuff that you've had in previous bio classes so this should be basically a review we're going to add a few tweaks to apply it to the microbes but for the most part um the basic Foundation of genetic structure and function is very very similar to to ours and therefore to what you've learned in the past let's go a and get started let's start by giving this chapter some relevance recall from previous chapters uh previous discussions where I have

um mentioned that bacteria for example or ARA for example are found absolutely everywhere you can possibly imagine some of the most extreme environments we've also talked about how uh bacteria have become antibiotic resistant so in order to understand this adaptability and changeability and this diversity we really need to look at the genetic level and it all comes down to mutation so a mutation is a permanent change in the DNA and the DNA is the the instructions for a cell so it's the instruction booklet to build a bacterial cell for example and if that genetic mutation

if that genetic information is mutated or changes then it's possible that the cell is going to change a little bit too maybe its proteins are a little bit different maybe its ribosomes look a little different or whatever now a mutation can be nothing you know uh it can be resulting in no change at all um they can also be harmful so in that case the cells would not survive but they can also be beneficial and in the case that they're beneficial those genes will pass on to uh their offspring and uh suddenly we have a

whole population uh of cells that contain and maintain this genetic trait uh recall that we talked about growth Curves in a previous chapter so here we're looking at stafl cacus orius as our example where 100 cells goes to 1.6 million cells within 7 hours so with a multiplication rate that high you know that fast to get a large population of cells and with a relatively High mutation rate you can imagine that we have there's a lot of opportunity in there to have some beneficial mutations so to Ill illustrate the power of mutation I want to

look at some human examples before we finish um CLE cell disease is one that we talked about with malaria and uh this is where hemoglobin is defective and it all really comes down to a single point mutation kind of like is shown in this picture here a single nucleotide mutated results in the case of CLE cell to in a huge protein it's completely defective again all because of one single mutation cystic fibrosis is a nasty disease it affects the lungs and uh uh is caused by a single point mutation taox is a neurodegenerative disease single

point mutation cancers we're all familiar with cancer and how how devastating that can be um these are not caused usually by point mutations it's usually an accumulation of mutations but nonetheless you see the power all right so now the next step is to understand the structure and function of DNA and then finally we're going to kind of come back at the end of this chapter and look at mutation again with our new knowledge all right there's a lot of information on this slide and the notes are brief because again this is supposed to be review

but what we're looking at here is um double stranded DNA so on the right side of the screen we see double stranded DNA so I'm going to circle one strand here oops and then the second strand so obviously my circling is not perfect all right several things to talk about here each strand is composed of nucleotides so I'm circling a nucleotide and we can go down here to see it's um blown up all right each nucleotide has a sugar component a ribos sugar it has a phosphate component and it has some sort of nitrogen containing

base there are four possible bases adenine or usually referred to as a thyine or just T guanine or G cytosine or C so we have a T C and G as options as as possible bases if we look at this all kind of put together um one nucleotide is attached to another nucleotide all and so on all the way down so we have this this uh phosphate sugar phos pH fate sugar phosphate sugar this is called a sugar phosphate backbone and it's highly negatively charged thanks to those phosphates the bases poke in toward the middle

all right so one strand of DNA is you know all these nucleotides are held together through strong calent bonds but one strand of DNA is bound to another strand of DNA by by these dotted lines that represent hydrogen bonds and hydrogen bonds are weak bonds but collectively they are quite strong so one hydrogen bond might be weak but a thousand of them is going to give us is going to give some Collective Strength notice that on one strand versus the other strand the bases pair up in very specific ways so a always pairs with with

t notice that they have two hydrogen bonds G always pairs with C and notice that they make three hydrogen bonds so that means if we know the sequence of DNA on one strand we can determine the sequence of DNA on the other strand and if we were to remove one strand completely so let's imagine that we remove this white this right strand completely if we were to just erase it then an enzyme could come in and make a new copy of that strand because it just reads the left strand as a template okay because of

these base pairing rules we can do that also because these two strands are held together through weak bonds an enzyme can go in there and pull the the two strands apart and the reason why I would want to do that is so it could read one strand as a template and this is going to occur during DNA replication and it's also going to to occur during transcription okay so another way to say what I've described here between these two strands and their base pairing is that they are what's referred to as complimentary so these are

two complimentary strands they match up they can they can pair up all right now let's look at one strand and notice that the top here we have a free uh phosphate group hanging out it's it's not touching anything above it and this phosphate is coming off of carbon number five this is the fifth carbon in the ribos sugar so this is called the five Prime end so the five Prime end has a five Prime phosphate coming off now let's look at the other end the other end has an o group hanging off that's not really

touching anything this is is coming off of the third carbon and so this is called the three prime end of that DNA strand and other words it's a thre Prime o so in other words the Strand has a five Prime end and a thre Prime end that are not the same another way to say that is there is a polarity all right notice the complimentary strand has a flipped polarity so the three prime is at the top of the screen and the five Prime end is at the bottom of the screen and so that flipped

nature is necessary for the hydrogen bonding to occur properly and this concept is referred to as anti-parallel so I can summarize by saying these two DNA strands are complimentary to each other and they are base pairing in an antiparallel fashion they they meet up in an anti-parallel fashion where the polarity is flipped between the strands now that we have the the basic structure of DNA down let's go ahead and sort of zoom out and look at how it's organized in a bacterial cell um all right so just a couple words that we've already talked about

but I want to reinforce um when we're talking about DNA the specific sequence specific region that codes for a protein product usually protein but sometimes RNA product uh is called a gene and a complete set of genes called a genome we also have these things called plasmas floating around and again we've talked about this before but there're small circular DNA molecules that are outside of the Bal chromosome um more on PL plasmas later all right in the procaryotes the bacterian ARA they their entire genome again there's no nucleus so it's in a a region called

the nucleoid that's the DNA containing region and the DNA uh genome is composed of a single large circular chromosome but this chromosome you know it's it takes up it would take up a lot of space and it be a giant mess unless it was organized so it's organized with proteins and it's organized with the cell membrane so the cell membrane is kind of serving as a scaffold to help organize this protein or this uh DNA and we also have um proteins that are assisting with super coiling and forming these these Loops that you see here

so we have these nucleoid associating Associated proteins or just a naps um you may remember um learning about histone proteins that sort of do the same thing in eukariotic cells so these naaps are helping organize the DNA um by allowing it to sort of twist around the proteins and then we have these other proteins that serve as Loop anchors and so on okay so we have this So-Cal Loop domain structure um so these these naps are organizing but also regulating uh the the expression of genes as well so turning them on turning them off so

so more than just organization here going on in the picture on the bottom left you can see what would happen um kind of a consequence of not having our DNA organized so uh it's not like this chromosome is just tiny and taking up a small region of the cell this is an equalized cell immediately after after Lis and the DNA has just sort of exploded from the cell so imagine all of that as a tangled mess shoved into the cell now obviously we need to organize it and we need to compact it and that's uh

that's why we're were worried about um you know forming these Loop domains and using knaps to help organize this stuff and compact it okay in this chapter we're going to talk about two major processes with DNA we're going to talk about DNA replication first and then we're going to talk about a process called gene expression so DNA replication is where the DNA duplicates itself and it needs to do that every single time a bacterial cell replicates every single time one bacterial cell turns into two bacterial cells first the chromosome has to duplicate itself self and

make a copy all right so to keep the process simple just going to look at this picture at the bottom there is an origin of replication called o r i c and that's where the enzymes assemble and open up the DNA Helix so-called initiation of DNA replication basically going to open up the Helix and start reading each strand each strand is going to serve as a template for a new strand to be made so in other words what we end up with here are two so-called daughter molecules and each one has one strand from the

parental DNA molecule and one strand it's light purple Here Pink that was made fresh this is called semiconservative replication keeps one old and one new but both strands are identical both daughter molecules are identical to each other and identical to the parental molecule okay so again they initiate the process at the origin of replication and then sort of continue their way through creating these so-called replication forks uh there's a lot of detail at those replication forks that we're not going to go over but I'll just say that it involves many many enzymes and DNA polymerase

three is the most important one this is the one that's reading the template Strand and adding nucleotides to make a new strand a complimentary a new complimentary strand um all right then uh a termination sequence is going to be reached and all of this sort of falls apart so that would be the termination piece of this again we end up with two daugh molecules each containing one template strand from the parental molecule and one newly synthesized complimentary strand of the many enzymes involved in the process of DNA synthesis the most important one is DNA plase

3 uh but this is also another one that I want to mention it's called topoisomerase and the reason why I want to mention this is because it serves as a target for some antibiotics and we'll talk about that at the end of this chapter so what topoisomerase does is it um eliminates super coils so what's a super coil well if we look at this chromosome here it's a double stranded DNA molecule that is a closed loop as a circle now imagine opening up the Helix in one spot and pulling it open right this is kind

of what's Happening uh when DNA polymerase 3 is uh making new strands at the replication forks you first have to pull apart the Helix and when the Helix is pulled apart and new strands are being made then we have this re we have this tension that builds up and this kinking that occurs Downstream or Upstream I guess I should say of the replication machinery and so when DNA Pumas 3 reaches that region it wouldn't be able to go anywhere there's too much tension it's it's all balled up so this enzyme topoisomerase will make a cut

on one strand and allow it to unwind one time and then it's going to reeal that cut so it's going to reeal that Strand and by doing that it has allowed the the the molecule to release some t tension so another way to say that is uh introducing some negative super coils by uh in order to get rid of some positive super coils so we're just releasing tension by cutting one strand letting it unwind and then sticking it back together Topo isase now all of this is really hard to visualize as especially when you're looking

at little tiny circles and little replication forks but I wanted to show you this picture and there's actually a video that goes with this um that shows how there's actually a lot of enzymes involved here at at the replication fork and it's called the DNA polymerase 3 holoenzyme complex and it involves a whole bunch of different enzymes including two DNA polymerases so let's look at the parental strand right here all right so that's the direction this Holo enzyme complex is headed and there's an enzyme that opens up the Helix right in the front and one

strand goes this way goes off to the side and the other one goes this way and each one of those is going to serve as a template for a new strand to be made now this bottom strand has the easiest case so there's a DNA Pumas 3 right there that makes the complimentary Strand and so we end up with a double stranded DNA molecule on the way out okay so that's one side the other side because of the polarity and because of some of the rules about how enzymes can only work in one specific Direction

it has to do kind of this crazy looping and stuff stuff so not interested in going all in all the details but I want you to see how even though on the most cartoons and in drawings of this it looks like the two replication forks are are spread out and they're they're doing things very independently but in reality as this little model shows um all of this is happening in one spot so pretty impressive um the last thing I'm going to mention here is uh and the video shows this um this this cranks along really

really fast and so DNA polymerase three on average in bacterial cells is able to replicate about a th000 nucleotides per second um something we can't really fathom you know to have have the nucleotide be the right match and to make a thousand nucleotides per second uh with very very few mistakes is pretty incredible our next topic is one of the most important topics in all of biology um gene expression gene expression can be summarized by this equation at the top and it looks like something was Lost in Translation here uh these should be arrows not

boxes but we're going to start with DNA which is our instructions it's very stable it's um it's copied from one cell to another one generation to another uh it's it's going to hang around for the life of the cell the DNA is coding ultimately for RNA or protein uh products and so we're going to think of the flow of information going like this DNA is going to be transcrip cribed to an RNA message it's called messenger RNA and then the messenger RNA is translated into a protein product again sometimes we just stop at RNA and

it's just an RNA product but most of the time it's going all the way to protein so we have this flow of information DNA to RNA to protein and it's called the central dogma or Central model of molecular biology you know this is how works we start with the DNA level and we get proteins proteins make everything they do everything you know they make the lipids of the cell membrane they make peptidoglycan for the cell wall they replicate DNA like DNA plase 3 does and so on and so on and so on all right so

the two processes transcription and translation let's think of it like this transcription is where you're rewriting something so we're not changing languages we're staying in the nucleic acid language so DNA and RNA are both nucleic acids made of nucleotides so DNA being transcribed to RNA we're staying in the same language we're just rewriting it from a DNA language to an RNA language okay but it's still nucleic acids right so that's transcription just rewriting translation is where you're transl ating one language to another so in this case We're translating a nucleotide code in the form of

mRNA into a protein or amino acid code so all of these are amino acids linked up to form a protein and you can see that translation is performed by the ribosome so the ribosome is our translator it's multilingual it can talk nucleic acid and it can talk amino acid all right so we're going to look at each of of these steps in detail before we get into transcription I just want to show you a brief comparison of DNA and RNA so first of all they are both nucleic acids and um there's just a you know

a few important ones I want to point out they're indicated with the Red Arrows um the sugar is a little bit different ribos versus deoxy ribos um here this is pretty important so DNA has a g c and T like we talked about before whereas RNA has no T has no thyine instead of the T it has uracil but the base pairing rules are basically the same uh a with u this time because there's no T and G with C all right the last thing down here that you see kind of a comparison is that

double stranded DNA really likes to be uh DNA in general really likes to be uh double stranded it's most stable as a double stranded molecule whereas RNA it can be double or single stranded okay so we have some of both um and I'll I'll show you what I mean by that in just a second so again apparently the arrows show up as boxes here but uh the first step here is transcription where we're staying within a nucleic acid language but we're just changing it slightly we're rewriting it from a DNA version to an RNA version

the enzyme that does that is called RNA polymerase so RNA polymerase is shown here kind of in this molecular model we have a double stranded DNA molecule and what RNA plase is doing is it is opening opening the Helix right there it's reading one strand as a template and it's synthesizing a messenger RNA molecule from that okay so mRNA is the messenger RNA and that is what's going to be translated now in bacteria for example this is occurring in the cytoplasm because there is no nucleus so right away a ribosome is going to jump on

this and start translating into protein okay we'll get to translation in a minute but I just wanted you to see how in bacteria for example that these are kind of happening right next to each other transcription and translation okay the last thing I want to mention here is um that mRNA is not the only type of RNA we have two other types R RNA is ribosomal RNA we've talked about that that before with taxonomy and uh as the name implies our RNA makes up part of the ribosome so it's involved in uh translation TRNA is

also involved in translation the T stands for transfer so this is Transfer RNA and we'll see how that works in just a minute before mRNA is translated sometimes it's going to be processed so as I mentioned before bacteria there is no processing okay so over here you can see that the RNA the RNA is immediately translated to proteins and it's often happening right they're they're often happening right next to each other transcription translation in UK carots for example that do have a nucleus the the steps are a little a little bit different so here we

have our DNA molecule that is transcribed to our RNA molecule the RNA molecule has regions called exons and introns exons in blue introns in red and before this is going to leave the nucleus those introns are going to be cut out and the exons are going to be spliced together so the introns are cut out the axons then are spliced together and serve as the mature mRNA that's going to leave the nucleus enter the cytoplasm and be translated by ribosomes again we're talking about a UK carot in this case all right couple things here so

the introns besides being removed they can also have some functions so it's it's not like they're just thrown away I mean that's possible but um often times they're going to be involved with regulating gene expression question the other thing I want to mention is that the exons don't always have to be spliced in this particular order so for example xon one and two might have um three in the middle so it might be instead of 1 two 3 it might be uh 132 and as the the ribosomes translate that you know that sequence is going

to be different and it's going to result in a different protein so wait to summarize that is one gene in the DNA can actually code for potentially code for multiple proteins and when we talk about viruses they're really really good at this because they have very small genomes with very few genes and so they can make a whole bunch of proteins from each gene through this RNA processing step our last step in gene expression is called translation and this again is where we're changing language we're going from a nucleic acid language in the form of

mRNA and we are making a protein product so we're converting that nucleic acid language to an amino acid language and the very specific sequences sequence of amino acids folds into a functional protein that's the goal of translation translation is going to involve the ribosome and it's going to involve a molecule called Transfer RNA R TRNA you see TRNA here on the left looks kind of like a a clover it's actually just a single RNA strand so from five to three prime we have this double stranded region and then we have the single stranded region right

here in yellow this hair pin Loop Loop then back to the doubl stranded and then another single stranded hair pin Loop and over here another hairpin Loop and then we have the three Prim end um we're most interested in the bottom and the top the bottom has a region called the anti-codon and um three nucleotides in particular make up that anti-codon which is why this cartoon version uh is sometimes used where so more on the anticon in a minute the other end at the very top is where the amino acid attaches so you can think

of TRNA as a decoder ring it's going to help the ribosome determine um it's going to help the the ribosome read the MRNA code and translate it to an amino acid code because the TRNA is involved in both it's going to interact with mRNA at the anti-codon end and it's going to be bringing in a very specific amino acid on the other end all right um let's worry about a code on on the next slide all right so let's go there next if we look at the top left figure GE this is a simplified version

which I think is going to help quite a bit we see the bottom hair pin Loop of the TRNA our anti-codon Loop it consists of three the anti-codon consists of three nucleic acids you can see the polarity has been given there too in red we have the MRNA molecule okay we already talked about how mRNA is made through transcription well it turns out that the MRNA is is written in threel chunks called codons so a codon is going to match up with an anti-codon so in this case the codon is ucg and we have the

complimentary anti-codon above it now keep in mind that this TRNA I'm just going to kind of draw a circle up here toward the top of the TRNA there's going to be an amino acid attached it's very specific so in other words this TRNA is matching the codon through complimentary base pairing and it's going to bring in the correct amino acid um as well to the ribosome so in order to determine which amino acid is going to come in to the ribosome you know which TRNA is correct for that codon we're going to use the genetic

code on the right so let's use our example shown in the figure of U CG as our codon so 5 Prime to 3 Prime U CG we can use this genetic code again this blue table here to find which amino acid that TRNA is going to have hanging off of it so to read this chart the first base is shown over here on the left the second base is on the top and the third base is on the right so the first base base again it's ucg so the first base is U so we find

that right here so we know that somewhere in here is our amino acid C is next that's the second nucleotide so we know more specifically that we're looking in this area right here and then G on the far right there that brings us all the way to right here and I kind of lined through it accidentally ucg codes for seene so Serene is going to be hanging out up here on the other end of the TRNA so in other words mRNA said to the to the ribosome the MRNA said put a sir here next that's

kind of what's what's happening here and then imagine another Cod on and then another one and another one and we just keep sticking in amino acid after amino acid growing a very specific amino acid sequence that ultimately was coded from the MRNA and ultimately from the Dr the the DNA not drna um so ultimately the instructions for all of this was in the DNA now let's zoom out and look at all of this together with the ribosome so first let's look at the ribosome on the upper right the ribosome consists of a large subunit and

a small subunits when they come together there are three binding sites for TRNA there's the E sit oops e for exit there's the P site this is where the growing polypeptide will be and there's the a site this is the uh where the new amino acid is going to come in all right um the on the left here we see that there's kind of this initiation setup where we have all these initiation factors these proteins that come together and and finally the the ribosome assembles and then on the next slide we'll see kind of the

step by step so let's go there okay this figure does a good job of showing the the pro the process in kind of one Fell Swoop so up here at the the top we have our our ribosome assembled with our mRNA and all of our nucleotides kind of poking up there we have a TRNA carrying in veine this is a very specific amino acid that it's carrying in and this TRNA is going to go into the a site in the P site we have an existing TRNA that used to be in the a site now

it's in the P site and it can contains the growing polypeptide and then the eite here has just recently had this TRNA that's empty and it kicked it out so that's the exit site so when this new TRNA comes into the a site let's go down to the bottom of the figure um here it is in place the amino acid chain a growing polypeptide is going to be transferred onto the incoming amino acid so it's not the opposite like you might expect the entire polypeptide is transferred on top of the new amino acid okay so

that means that the the TRNA that's in the P site after it transfers the the protein over it's going to be empty so that TRNA is not going to have anything anymore all right now imagine the ribosome shifting down to the right one codon and when it does that the TRNA that's currently in the middle will then be in the E site and it's going to get kicked out this one that's currently in the a site is going to have the growing polypeptide and it will be in the P site and the a site will

then be open and available for another incoming TRNA we just repeat the process all the way until we reach a stop code on which is shown on the next slide so to terminate translation a stop codon needs to be reached and I forgot to point this out in the genetic table the genetic code table um where we were matching up amino acids to codons but there are three stop codons so instead of coding for an amino acid they code for termination of the process so when a stop codon is reached a a termination Factor will

bind and the termination factor is it's kind of like a an mtna it doesn't have an amino acid attached but it has a very specific purpose of causing everything to disassemble so when the termination Factor goes in there everything gets kind of kicked off of the MRNA and we are left with our protein and this protein will fold in three dimensions very specifically and it will fold very specifically based on its amino acid sequence and after it's folded into a specific threedimensional shape it can then function as a fully functional protein I want to introduce

this concept called a read called a reading frame um with regard to translation so let's start with uh let's start with this first three nucleotides here AG so when this is transcribed and translated HG is going to be a codon basically um and so because the ribosome reads the MRNA in three-letter chunks uh you can imagine in blue here this is a three-letter chunk this is a three-letter chunk this is a three-letter chunk and so on so it's going to be inserting the ribosome is going to be inserting very specific amino acids according to that

frame of reference but what would happen if the ribosome made a mistake and instead of starting with a uh started right here with G as the first nucleotide okay then instead of AG GG as our first codon it's actually going to be ggt which will result in a totally different amino acid being put in that that spot so what we've done is we've shifted What's called the reading frame I like to just sort of think of it as a frame of reference you know we could do the same thing and start with the second G

and that would give GTG as the first code on instead of the other options so we have three possible reading frames and each reading frame is going to very likely result in very very different uh protein products and this is going to be important when we talk about mutation shortly okay here we are we've come full circle we started the chapter by talking about mutations and we're going to finish the chapter by talking about mutations and now we're prepared to understand the details of how these mutations occur and the effects that they have okay so

I've already mentioned that mutations are permanent changes in the DNA and ultimately they're going to affect RNA and protein through transcription and translation and there are multiple causes for mutations some of those are physical and chemical causes good example would be ultraviolet lights UV radiation um we also have these things called base analoges so an example of that is shown down here where on the left we have normal thyine and on the right we have this one that has a bromine on it so it's very very similar in structure but when that is incorporated into

a growing DNA or RNA chain then it's the base pairing is going to be thrown off and uh it's going to not be replicated accurately so it's basically going to result in mutation uh when the DNA is copied okay and this is going to be useful in um some antimicrobial drugs you know to try to Target microbial uh metabolism in in DNA synthesis by disrupting their uh DNA synthesis process okay um some ways that mutations let's talk now about some different types of mutations so we've already talked about why they're important um we have these

so-called jumping genes that can interrupt Gene sequences and kind of cause mutations that way and then we have what are called point mutations which is what I talked about in the beginning of the chapter and they're they're kind of mentioned here but I'm going to wait until the next slide to actually go through what they what they mean okay here we have all of the different types of mutations um point mutations and uh insertions and deletions so let's start with point mutations here is our normal situation in this example okay so normal mRNA sequence at

the top Aug C A ACA and so on and then the corresponding amino acid sequence okay let's say that in the second codon which is normally C A we have CAA so CAA instead of c a so the a replaces the G now if we look up what CAA codes for in the genetic table the genetic code we're going to see that it codes for glycine right there and it turns out that our original one was glycine so this is an example where the mutation doesn't cause any problems uh it's called a silent mutation so

even though there was a mutation the amino acid code is the same silent mutation the next one is called a Miss sense mutation so now let's look at the same Cod on c a coding for glycine that's normal instead of c a it's a a so the first nucleotide of the codon has been mutated from a c to an a if we look that up in the genetic table we see that it codes for lysine which is a different amino acid than than uh glutamine so in that case even though only one amino acid has

changed it could potentially have a pretty significant effect on the final uh folded protein it might not have much of an effect but it also might and a good example of that is Cle cell anemia it's a single amino acid that results in the defective hemoglobin so that that can be pretty significant that's called a Mis sense mutation where a single amino acid does change a non-sense mutation is where a stop codon is inserted through mutation so instead of c a it is is u a and if we look that up in the genetic code

we're going to see that UAG is a stop codon so the termination Factor binds and everything falls apart so in other words a nonsense mutation results in a shortened protein and very very likely that's not going to be uh functional or normally functional anyway okay those are point mutations silence missense nonsense now we have deletion and insertion mutations both of these result in a frame shift which is going to be pretty significant on the outcome so let's look at the second and third codons it's usually c a AA and here there was a deletion so

instead of c a gaca we lost an A so it's now c a g c auau and if if we look that up the caou codes for histadine instead of threonine like it normally does like the the normal sequence was and everything Downstream is different too and that's because a frame shift has occurred so this is likely to have significant outcome in the final fold of protein we can do exactly the same thing exactly the same idea except by inserting an additional nucleotide that's going to cause a frame shift and everything Downstream is affected so

again to apply this to the microbial World um once we you know once we understand these processes it becomes kind of apparent that any one of those processes is critical for a cell to live and a for a cell to replicate and that makes these great targets for antibiotics so many of the antibiotics that exist Target gene expression and Target D synthesis um so we could Target transcription by messing up RNA polymerase there are many examples at Target translation by preventing initiation uh blocking binding SES preventing movement of the ribosome premature termination so the macrolides

are a class of antibiotics we talked about previously the target translation um they might bind to the subunits and prevent assembly in the first place and so on uh DNA replication can also be targeted so remember we've talked about the floral quinolones as a class of antibiotics that Target DNA synthesis and they toet target Topo isomerase and as we see up here remember to isas uh helps um release ease or release the tension of super coils that form as the Helix is Unwound during DNA replication and it does that by making a cut in one

strand allowing that strand to unwind once and then stick that strand back together but what these antibiotics do floro quinolones is they allow the topoisomerase to make the cut but they don't allow it to reeal the Strand so we get all these Cuts in the Strand ultimately fragmenting the DNA and killing killing the cell's ability to replicate its DNA