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Microbiology Lecture 4 Penicillin Mechanism of Action

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For you guys welcome back microbiology mechanism mechanism of penicillin mechanism of penicillin this is not pharmacology of penicillin just wanted to explain how the penicillin acts and the reason for doing that is that i just finished the last two lectures in which we talked about the cell wall structure and the mechanism is very pertinent to that structure discussion

So you can actually combine these two and understand it so let’s talk about gram-positive and gram-negative what i am going to do is i’m going to draw gram-positive here the cell wall and gram-negative cell wall here then we’ll put penicillin on it and see what happens to these bacterias so now let’s say this is the you know that the that the peptidoglycan layer

So if i can go here and make the cell wall for a reference what’s a bacterial cell membranes so this is the plasma membrane bilayer lipid bilayer right this is the internal most membrane outside this in the gram-negative three layers of peptidoglycan in gram-positive up to sixty layers of peptidoglycan sand the peptidoglycan are supposed to have been cross-linked

With each other through their peptide so this is peptidoglycan so it has ag like and part which are sugars and then it has peptide part which are peptide oh so the peptide parts are cross-linked so we are going to talk about how that cross-linking occurs and how penicillin works penicillins function is to remove or to block these cross-links and by that disrupt

The peptidoglycan layer peptidoglycan layer and ultimately cause bacteria to break now on the gram-negative side you have so let us just make it this way this is positive side this is gram-negative bacteria when a gram negative on a gram positive bacteria lots of more peptidoglycan layers on the gram negative bacteria this is the periplasmic space and above that

Is the another lipid bilayer with lipopolysaccharides lps this is the gram-negative side this is gram positive sign and again the so first let us understand what these cross cross linkages are then let’s see how penicillin blocks them we would also see why in gram negative penicillin is not as effective as it is on the gram positive so let us see that so let’s

Say we make the peptidoglycan layer over here to make that what we will do is peptidoglycan layer is made up of glycans which are sugars and these sugars are alternating between n a em n acetyl meramec acid add n ag energy n acetyl glucosamine n acetyl n-acetylmuramic acid and n acetyl glucosamine these are the alternating sugars that make a backbone and there

Are many such backbones there are many such threads of sugars so let me make one more here so again what do we got here n ag n a m n ag n am these alternate that is the rule so now what happens is with every n am there are tetra peptides attached for amino acids are attached the fourth amino acid this amino acid is always this amino acid the fourth amino acid is

Always d-alanine and remember dd is normally a synthetic structure it is not usually seen in organic substances organic substances normally are levo but this is one place where you would see d ln e know dextrose now let me make the same structure here so this is the structure and this is the structure so these are two threads and they have two protein structures

Attached with them now what happens is there is an enzyme called transpeptidase transpeptidase enzyme transpeptidase enzyme what it does is it picks up two protein chains that are side by side and creates a cross link between the fourth amino acid and the third amino acid so if i make them here 1 2 3 4 & 1 2 3 4 so this is let us say n ag this is n am this

Is another n am what it would do is it would take the fourth amino acid and collect it to the third this function is done by the transpeptidase enzyme there are two types of cross linkages you would see in e.coli for example the linkage will be that nm n ag nm when they combine with the other so let’s make another nm i’m making it slightly moved so we’ll be back

In one quick second okay so we are talking about this at in e.coli for example the fourth and third the third is lysine or glute glucosamine sorry lysine or something i forgot and this one is elenin what happens is the cross-linking uses one two three four five glycine’s to connect them these are glycine’s glycine’s so in case of some bacterias the cross-linking

Itself so if i make them here again nm and ag nm one two three four one two three four the cross-linking of four to the third uses glycine to do that this is glycine so this happens in some cases and in the other cases these two directly combine so that is how the structure is and how would they directly combine check this out here here one two three four one two

Three four and you connect them right so that is how they combine in case of some bacterias and this is another way of combining in case of other bacterias but this combination this cross-linking is done by the transpeptidase transpeptidase what does penicillin does but penicillin do is that it comes to the transpeptidase so let us say this is the transpeptidase

It comes and it binds in it this is penicillin when it binds inside the transpeptidase transpeptidase cannot bind with these things and cross link them that is when the peptidoglycan layer starts becoming disrupted and bacteria breaks up why does it break up because the osmotic pressure inside the bacteria is more than outside now why does this not happen to

The gram negative bacteria because penicillin cannot penetrate through this outer wall outer wall has poor eenz outer wall has poor eenz which allow the substances to go in but the pouring has specific channel size and structures so penicillins cannot easily go to the peptidoglycan and do this action that is where gram-negative bacteria are usually not prone to

Penicillin but gram positive bacteria are now how does vancomycin work what vancomycin does is it does the same thing it also breaks the factory took like a layer but instead of disrupting the that transpeptidase but vancomycin does is it’s very clever it goes and attaches to the d-alanine this is vancomycin when comai see so once it attaches to the d-alanine

Now the transpeptidase has to come here and collect these two but because this site is already occupied transpeptidase cannot do its function and that is how the cross-linking would not occur and peptidoglycan layer would stay weak and that is again that is the mechanism of action for vancomycin both of those are very interesting i really love the this mechanism

Although bacterias have evolved their transpeptidase is do not allow the the penicillin to bind for example they are made their transpeptidase look like this and this is just a theoretical diagram so now the penicillin cannot go in but they can still function however vancomycin is immune from any evolution of the transpeptidase because become a machine does not

Interact with the transpeptidase it actually just connects with the fourth peptide amino acid on the cell wall on the peptidoglycan cell wall so this is it for the mechanism of action of penicillin

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Microbiology Lecture 4 Penicillin Mechanism of Action By Drbeen Medical Lectures