Wednesday, 28 May 2008

How does penicillin work?

According to their mechanism of action, antibiotics can be divided into three large groups:
  • Those inhibiting cell wall synthesis
  • Those inhibiting protein synthesis
  • Those inhibiting nucleic acid synthesis

Penicillins and related compounds all prevent susceptible bacteria from creating a cell wall.

Why is a cell wall important? Like most biological membranes, the cell membrane (not 'wall') of bacteria is semipermeable - that is, while water can pass through the cell membrane without too much trouble, many osmolytes are prevented from doing this. As you may remember from physiology, this allows for osmosis to occur. The inside of a bacterium is packed with enzymes and other molecules, and its osmoloarity is significantly higher than the average extracellular osmolarity. Thus, there is an osmotic pressure that would tend to 'force' water molecules into the cell. All things being equal, bacteria would therefore all swell and eventually burst within a few seconds.

Enter the cell wall. This structure's primary function is to resist the tendency for the bacteria to swell and burst due to osmosis. (More scientifically, it resists the turgor pressure.) So, it's not hard to imagine why any compound that blocked a bacterium's cell wall synthesis would effectively kill it. And this is exactly what penicillin does.

You can stop reading right now if that's enough detail for you. However, if you want specifics, read on...

A large component of all bacterial walls is a substance known as peptidoglycan. Gram positive bacteria have cell walls made almost exclusively of peptidoglycan, whilst the proportion of the Gram negative bacterial cell wall it constitutes is considerably less.

Peptidoglycan is principally made from two sugar molecules. Their names are N-acetylglucosamine and N-acetylemuramic acid, but we can call them NAG and NAM. Bacteria synthesise long linear chains of these two sugars, alternating between a NAG and a NAM.



Attached to each NAM, however, is a chain of a few amino acids (an oligopeptide). [Interestingly, these amino acids aren't found in proteins, and this may allow them to escape degradation by our most common proteases (enzymes that cleave proteins).] To complete the structure of peptidoglycan, these oligopeptides are cross-linked to a neighbouring chain's oligopeptides to form a strong mesh.

What penicillins do is to irreversibly bind to the bacterial enzyme that cross-links these chains. The unfortunate enzyme's name is transpeptidase, though is sometimes (rather anthropocentrically!) referred to as "penicillin-binding protein". This binding deactivates the enzyme, and so no crosslinking of the 'amino sugar' chains can take place. And we've already mentioned how catastrophic this is for an aspirant bacterium...

Incidentally, it is also immediately clear why penicillins tend to work better on Gram positive than Gram negative organisms - Gram positive organisms are simply more dependent on peptidoglycan for their cell walls.

One other interesting point: you may know that tears have weak antibacterial properties. This is principally due to the fact that they contain lysozymes. These compounds go to work by breaking down the bonds between the sugar residues (NAM and NAG). The end result is almost as if tears had secreted their very own penicillin molecules!

36 comments:

  1. Is it true that penicillin comes from a mould?

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  2. Yes, originally. Fungi hate interfering bacteria just as much as us, and (also like us) have evolved numerous biochemical substances designed to thwart them.

    A particular fungus now called Penicillium chrysogenum was noticed by Alexander Fleming and others to kill some types of bacteria. As it turns out, it accomplishs this by secreting... penicillin, under conditions of stress.

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    1. actually it was a different strand that was notices the Chrhyzogeum strand was later foundin america when Florey was working on it in America and the pencillina used today is much different from the original fungus

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  3. this site really helped me write my osmosis essay asking how penicillin uses osmosis to destroy bacteria

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  4. Sharie also for the last time22 October 2008 at 23:48

    this site is THE BOMB it really actually cmpletely answered my question and basically finished my essay. -thanks o and thans 'Jeremy' for answering 'Steve's' question it was my question too! (i'll stop commenting now)

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  5. Comment away Sharie - I'm glad it helped!

    Jeremy

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  6. thanks for the great site it really helped me complete my essay

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  7. What's your full name? And when is your date retrieved? I need to know for my bibliography because I use your website as a reference.

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  8. For the date retrieved, simply use the date at which you viewed the page. For the name, use "Medic Guide", so that the final result would look something like this:

    Medic Guide, "How does penicillin work?", http://medicguide.blogspot.com/2008/05/how-does-penicillin-work.html; accessed 19 January 2009

    There are different styles of referencing, however, and you should simply use the one that is expected of you for now. It is quite acceptable to put the name of the site rather than the author's name.

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  9. ok...thank you very much.

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  10. YAY PENICILLIN!

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  11. yea it is that it came from a mould!!!! pencillin vs. the body crimmals lol!!!

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  12. Thanks Alot I Thought that i was the only person on the internet intrested behind the chemistry of penicillin

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  13. Thanks. Helped me a lot with physiology homework

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  14. all, thanks alot for great site - i have a cold and feel like crap and knowing that penicillin is doing helps!

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  15. Dont swell, avoid H2o, and take care about your net of proteiglycans!!!

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  16. Great!!! I am doing my A levels on my own as private candidate and no one to teach me. Now I know how penicillin works, website made it easy, I have book marked this website...thanks.....!!!

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  17. how does it work?

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  18. Thank you for this site. I am wondering if it is counterproductive to take pro-biotics during the course of penicillin, or am I wasting money on both counts? Does the penicillin get absorbed in the stomach and go directly to the blood stream? Does it get to the root of the tooth before it would get to the colon?

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  19. Probiotics are a contentious issue, I'm afraid. They tend to be vigorously promoted by individuals and groups outside of mainstream medicine, rather than within it (which I've learn to interpret as a warning sign). They have been shown to help in some conditions, but the effects have almost universally been quite small. Furthermore, they are known to be harmful in certain circumstances too.

    My advice in general: one shouldn't worry with probiotics if one is just getting the odd short course of oral penicillin. They probably aren't active counterproductive either, on the other hand.

    HOWEVER, your individual set of circumstances would need specific attention, and so if you're concerned, I'd visit a health professional.

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  20. i am in a project lead the way acadamy of biomedical sciences. its a tough course for high school students and this site gave me exactly the information i needed and more.

    Ps-- i got an A on the assignment. :)

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  21. im a patient i had a an anal fistula 2 operations etc then my abcess flared up again so doc perscribed me flucloxacillin 500mg and after 4 days it cleared up i was in so much pain thanks doctor murray

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  22. penicillin killed the bacteria on my body

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  23. This article really helped, and by the way, the picture in your article, is it of Penicillium, or .... ?

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  24. FANKU!!!! This has really helped with my AS Chem work!

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  25. Am doing a degree in Biomedical science, this really, really helps me to understand how penicillin works :-D

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  26. This is very clear & well diagrammed. It made me want to learn more about microbiology. Thanks.

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  27. Im gonna get an A easy bread! :-)

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  28. easy to understand and very clear explanation . Thanks a lot. Really helped me to study for my microbiology exam.

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  29. I've had a sore throat for some time now. After doing some research online, I thought it was probably a bacterial, rather than a viral infection. I went to my doctor and he confirmed it was strep. I am on a course of antibiotics and was wondering how the whole thing (sore throat infection and cure via antibiotics) worked. Your site explains in a highly intuitive way what is going on in my body. My curiosity (and the pain in my throat) have both been quenched - Thanks so much!!

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  30. This comment has been removed by the author.

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  31. Transpeptidase is the enzyme that bulids cross-links, but what is the name of the enzyme that causes the step in peptidoglycan synthesis when the bacterial cell elongates before it divides?
    Thanks!

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