all right engineers in this video we're going to talk about antibiotics all right so the way we're going to do this is we're going to go through at multiple different types of antibiotics we're not going to cover all of them it would just be impossible to cover all of them and all their different effects and mechanisms of action we're going to start off by looking at antibiotics that are affecting the cell wall so it's going to start there so if you look here now bacterial if we're talking about grandpa's anima gram-negative bacteria we'll make a video on this but gram-negative and gram-positive bacteria really just differ and their overall like if I were to have let's say I take for example here I take two bacterial cells just real quickly let's say here's the bacteria and here's the bacteria let's say this is gram-negative and let's say this is gram positive the real big difference between gram-negative and gram-positive is that when you to look at gram-negative bacteria they have a very thin peptidoglycan layer so they're peptidoglycan layer that we're going to talk about that is very thin and another thing is that they have a cell membrane an outer cell membrane surrounding that peptidoglycan layer and they have little pores inside of it right so little porins a gram positive bacteria is the exact opposite it has a very very thick peptidoglycan layer a very thick peptidoglycan layer okay and that is going to be our grand positive so we're looking at gram positive and gram negative bacteria it really is important to kind of have a basic idea of what their overall cell wall looks like an overall cell structure is consisting of okay so again one more time gram-negative has a very thin peptidoglycan layer but as an outer cell membrane it also has what's called lipopolysaccharides with lipid a and let me probably saccharides and stuff like that that are the toxins and I'm here grand positive bacteria just as a very thick peptidoglycan layer but no outer cell membrane okay so now that we know that let's go ahead and dig into antibiotics so the first antibiotics that we're going to talk about here we're going to talk about the beta lactams okay so we're going to focus here on our beta lactams now what is a beta lactam now just really really quickly it has a specific structure so if you look at a beta lactam usually you have a 5 ring structure here and then you have a little 4 ring structure right here and then you have a little carbon eel and then you have this little nitrogen group here so it's kind of like a cyclic amide this right here is the beta lactam this component here this is the beta lactam so these beta-lactam antibiotics you usually have this beta-lactam ring which is incorporated into it okay the beta lactams we're going to focus on here we're going to focus specifically on the penicillins so we'll talk about penicillin specifically like penicillin G and then we're going to talk about amoxicillin okay so amoxicillin and then we're going to talk about cephalosporins and we'll talk about all the generations of cephalosporins okay before I do that let's take a look at the overall cell wall structure again just a little bit more in depth zooming in on that peptidoglycan layer if we look in the peptidoglycan layer what is the peptidoglycan you see these blue structures right here those blue structures are specific derivatives of carbohydrates like glucose so what do I mean there are made up of structures which is called NAMM and nag so they're just derivatives of glucose n am NAMM stands for in acetyl uric acid in Ag stands for in acetyl glucosamine all these are these blue structures here they're just derivatives of our carbohydrates like glucose okay now coming up off of these carbohydrate residues you see this like a violet structure coming up out of this that right there is like peptide bond is actually a pentapeptide and then across from that again you're going to have another what would this be this would be another an acetyl Meramec acid and this could be another and acetyl glucosamine these black proteins are coming downwards from this part to this is another pentapeptide and if you look there this little orange structure that's the cross link between them that's the peptide bond between them right so this is the basic structure of our peptidoglycan layer in a zoomed look you see this little orange guy just kind of sitting down that's our penicillin binding protein so that little red structure right there which is actually going to be sitting down there on the cell membrane is going to be the penicillin binding protein so what is this guy here called he's called the penicillin binding protein okay he's a pretty important structure here because he's going to what he's really what a lot of these actual beta lactams are binding on to alright next thing if you look here these brown scissors those are little auto lytic enzymes so we're going to talk about them and then these little C like orange enzymes there they're called beta lactam ASIS ok so this little orange structure up here this orange structure here is called beta lactamase and then these little brown structures they are actually going to be called Auto lytic enzymes okay now that we've done that let's go over these antibiotics here alright penicillin first so penicillin it's it is able to treat in general gram-positive and gram-negative bacteria however over the past you know years certain bacteria have become resistant to penicillin okay how have they become resistant to penicillin okay this beta lactamase there's a specific part of it today beta lactamase so it's an enzyme right so look what it can actually do I'm going to draw that beta-lactam ring over here and it's got that double bond right there with the NH and then it's got the little five membered ring there this is our penicillin if we give someone penicillin who already has bacteria that are very resistant to the penicillin what do I mean maybe they have plasmids that allow for them to produce this enzyme called beta lactamase what will the beta lactamase do though it'll break the beta-lactam ring if it cuts the beta-lactam ring this penicillin is not going to be able to bind to this penicillin binding protein and mediate its effects so because of that this will be rendered ineffective so that is the importance is that certain bacteria become resistant by developing beta-lactam Isis so really it's more effective now just being able to treat gram positive bacteria with a little bit of gram-negative coverage so what type of bacteria is it a recover if you may it can cover streptococcal okay that's the main one it can cover streptococcal bacteria so any type of streptococcal bacteria okay it was able to develop you know in the past treat you know staphylococcal bacteria but again they've developed resistance also so streptococcal bacteria it's also able to treat syphilis okay so just a little bit on the penicillin so what does penicillin actually do how does it mediate these effects that it can actually kill these bacteria because it's bacteria SCYTL meaning you can kill the bacteria so let's say here here's the penicillin what the penicillin does is it comes in and it binds on to this penicillin binding protein so let's say that we draw that here here's the penicillin and he binds on to this penicillin binding protein when he binds to the penicillin binding protein he stimulates the penicillin binding protein and what this penicillin binding protein does is it takes its hand and it comes up there and it stimulates these brown enzymes so then what does it do it comes up here and stimulates these auto lytic enzymes if these auto analytic enzymes are activated what are they going to do they're going to start cutting up these bonds these peptide bonds these glycosidic bonds and it's going to start altering the overall structure of the cell wall that's one thing that happens second thing that happens there's a lot of other enzymes here there is other enzymes that actually link these peptide bonds together between these little pentapeptides so you get for having different types of transpeptidase enzymes whenever the penicillin binding protein is stimulated he inhibits the transpeptidase is from cross linking these pentapeptides and if these are no longer cross-linked the cell wall starts becoming disrupted now when the cell wall is disrupted it allows for water to start leaking into the bacterial cells and when water leaks into the Piersol eventually can cause the cell to lyse that is the way penicillin works so again one more time because all the rest of them are gonna do the same thing so once we know penicillin we know what these functions are - so one more time what does penicillin do penicillin comes in binds onto the penicillin binding protein stimulates him when he becomes stimulated he stimulates these Auto lytic enzymes who start cleaving and breaking up the cell wall then he also inhibits let's say that I draw this enzyme out here I'm just going to draw some little dude out here here's this little dude and he's got his hand in this bond right there okay these are transpeptidase enzyme what are these transpeptidase enzymes doing they're helping to link these actual pentapeptides he will inhibit these transpeptidase enzymes so now they can no longer cross link these little peptide chains and because that the cell wall will be disrupted once it's disrupted water can leak in when water leaks in to cell lysis okay so we're set there amoxicillin same mechanism of action cephalosporins same mechanism of action but now amoxicillin he is very very susceptible to these beta lactamase is very very susceptible so when you give someone a moxa stealing you usually want to give it to them with clavulanic acid clavo lonex acid why do you want to give that because clavulanic acid is a beta-lactamase inhibitor so if you give them clavulanic acid what is it going to do it's going to inhibit the beta lactamase enzyme if the beta lactamase is inhibited now this amoxicillin is going to have more available to start exhibiting this effect okay so that's the job of clavulanic acid what can a moxa sill entreat it can treat a lot of different things so amoxicillin is good at being able to treat urinary tract infections he's going to being able to treat respiratory tract infections he's also good at being able to treat meningitis and he can also treat infections that are caused by salmonella - so we can also treat infections caused by salmonella and you know he's also really good at being able to treat middle ear infections on Titus media too so Titus media middle ear infections right okay so that is going to be the amok Ahsan so he's going to be able to treat urinary tract infections respiratory tract infections meningitis salmonella otitis media okay cephalosporins mechanism of action same thing activates the penicillin binding proteins and inserts all those effects cephalosporins though are very interesting okay so there's four generations of cephalus horns right so let's go ahead and go over those real quickly so their first generation so we could say first generation so first generation is actually going to be we could take for example cephalexin so cephalexin is one example here of a first generation cephalosporin then we could take for example a second generation now a second generation will be like Seth a rock scene set for rock scene okay and then we could take for example a third-generation cephalosporin so a third-generation cephalosporin could be like ceftriaxone and then there's even fourth generation so fourth generation would be like cefepime so fourth generation would be like cefepime now why am i mentioning this well the reason why is cephalosporins the first and second generation are really only good at being able to treat mainly gram positive bacteria so these are really only good at being able to treat gram positive bacteria okay whereas what's happened over the years is that the ceftriaxone and the SEPA pean have actually had a little bit more ability to treat more of the gram-negative bacteria okay so again first generation could be like cephalexin and second generation could be like cefuroxime but the big takeaway is these aren't really used anymore but they're good to treat gram positive third generation fourth generation have a little bit more gram negative coverage so except try Oksana cefepime okay so what would be the coverage so for example let's say that I used cephalexin and cefuroxime they really only have grand positive coverage so what I really use these guys for I would probably use these guys for more of your Staphylococcus aureus and streptococcus pyogenes so even streptococcus pyogenes okay now if we use ceftriaxone and cefepime they can treat gram-negative so what can I use that for I could use that to treat them they have a lot of good things that they could treat now Pseudomonas is a really big one they can treat Pseudomonas so like Pseudomonas aeruginosa they can treat certain types of bacteria that cause meningitis um they're also pretty good at being able to treat infections caused by Klebsiella so Klebsiella which is very common a bacteria that can cause pneumonia so pneumonia so this is actually a bacteria that cause pneumonia more commonly it can cause other infections but more commonly pneumonia and even other different types of entero bacteria so even different types of inteiro bacteria all right so that's our cephalosporins there is other beta lactams and different types of penicillin derivatives that I could have mentioned like pip Tazo I could have been to mention carbapenems you know a pip Tazo can treat Pseudomonas carbapenems are actually going to be able to treat very very problematic abdominal infections so they can treat that too all right but that's pretty much going to cover our beta lactam so a quick review and we're going to move on to the next ones really here we go penicillins what do they actually do they're going to come down here by onto the penicillin binding proteins then what activate the auto lytic enzymes which we're going to cut up some of the cell wall structures disrupting cell wall also penicillin binding proteins are going to inhibit these enzymes that are called trans peptidases so if you inhibit them they can't cross link these actual peptide chains cell walls disrupted what happens as a result water leaks in and then eventually cause the cell to lice and kills itself so these are bacteria sidle you need to kill the bacteria what could be certain types of beta lactams penicillin amoxicillin cephalosporins right and I can even included carbapenems or pepper selling with hazel back in like pip Tazo but again what is penicillin treating grand positive and gram-negative mainly streptococcal because there's a staphylococcal bacteria become resistant he can also treat syphilis what about amoxicillin he's very very sensitive to the beta lactamase is who cleaved the beta lactam rings so in order to make them effective what are you give them with clavulanic acid what can they treat UTIs respiratory tract infections bacteria that cause meningitis salmonella otitis media okay and then cephalus points you said there are four main generations there is five fifth I said can you eat Marissa first generation second generation are mainly for gram positive first generation could be like cefalexin second generation could be like cefuroxime so they can treat Staphylococcus aureus and streptococcus pyogenes okay and then third and fourth generation are more for the gram-negative coverage and so those third generations to be like ceftriaxone and cefepime right what can they treat like Pseudomonas aeruginosa meningitis Klebsiella which can cause pneumonia as well as entero bacteria okay what other kind of drugs affect the cell wall because there is other drugs besides these ones very very powerful one we have to mention this one this very very powerful one is actually called it's like glycol peptide so let's actually put that down so let's actually this is actually a group under the glycol peptides so what glycol peptide is this this glycol peptide is very very strong this is called Vanko Mison and vancomycin is actually really good at being able to treat mersa what is what is Marissa Marissa stands for methicillin-resistant Staphylococcus aureus now methicillin is an antibiotic but they don't really use that anymore okay but certain bacteria have become resistant right to penicillin or methicillin so you have to give Vanko because that can kill the Marissa okay now venko is actually really good mainly at being able to treat gram positive bacteria okay so like MRSA and c-diff so Clostridium difficile colitis so it's good at being able to treat c diff so c diff is the one that makes you pee out your butthole all right so it's really nasty one really really infectious diarrhea and it also can retreat certain types of bacteria which are like resistant resistant coagulase so coagulase negative now remember i'm saying negative resistant coagulates negative bacteria okay and this is Vanko so vanko's are pretty powerful antibiotic now what does vancomycin do he does something different he has the overall same effect of these beta lactams but different mechanism of action what exactly is he doing thank ou is very very interesting so you know that every protein usually has what's called a carboxy terminus and then as an amino terminus right and then really if I were to show the peptide bond correctly it's really what's linking in this part together right here's what's interesting let's say I take Vanko if I give someone Vanko look what it's doing it's binding onto this carboxyl end when it binds onto the carboxyl end this can't form a peptide bond so now what happens is vancomycin binds onto the carboxyl end of these actual peptide chains and if it blocks onto it Xterra Clee hinders that peptide bond formation so now if you can't form a peptide bond this cell wall is disrupted if this cell wall is disrupted what happens water flows in as water flows in what happens the cell lysis so this is a bacterial cell antibiotic okay so one more time what does Vanko doing it's binding onto the carboxyl end of these peptide chains as it binds on to the carboxyl end it's sterically hindered this amine group from being able to form a peptide bond and as a result of cell wall is disrupted water enters in and the cell lysis so it's a bacterial Seidel antibiotic okay so we've covered our glycol peptides now let's go over here let's cover a very weird type of bacteria that's not for grandpas and for gram negative bacteria okay so this one that I'm going to talk about is mainly important for being able to treat tuberculosis okay so it's mainly used to treat tuberculosis so caused by the Mycobacterium now Mycobacterium don't have a cell wall that's made up of peptidoglycan they are made up of these little orange structures you know what these orange structures are called they're called mycolic acid so can you see this enzyme right here this blue enzyme this blue enzyme is called a mycolic acid synthase source in space it's called I so nyeh SID and again what is this antibiotic do this antibiotic is mainly treating tuberculosis caused by the Michel bacterium so what it does is it has a specific point word actually here let's say here's the isoniazid it's actually going to come in and inhibit this mycolic acid synthase our synthetase enzyme if this enzyme is inhibited can it synthesize the mycolic acids to make up the cell walls no and if it can't synthesize this mycolic acid the cell wall integrity is altered if the cell walls integrity is altered can that cell survive no water might flush into it and cause the bacteria to die so again isoniazid is used to treat tuberculosis caused by the micro bacterium it's cell walls consisting of these mycolic acid residues what happens is if you give ionize it and hits the mycolic acid synthesis or synthase enzyme which then can no longer synthesize mycolic acid if it can't synthesize mycolic acid the cell walls integrity is altered and then what happens the bacterial cell dies okay alright guys so that pretty much covers on this part the antibiotics that are treating for specifically the cell wall synthesis and structure in the next video we're going to talk about the antibiotics that are mainly used to target the folic acid pathway