PDA

View Full Version : Penis-illin you?



jubei33
15th October 09, 09:18 AM
Chemistry that Changed the World: B-Lactam Antibiotics

“Wolf’s liver taken in thin wine, the lard of a sow that has been fed upon grass, or the flesh of a she-ass taken in broth.” --Pliny the Elder

We’ve come a long way in some ways, at least since “flesh of a she-ass” was considered a specific remedy from disease. Though, did you know that blue moldy bread was a medieval remedy from infection? The blue mold was presumably a kind of Penicillium fungi. On that fine day in 1928, Alexander Fleming had no idea he would discover something that would change medicine forever. After coming back from vacation and sifting through the piles of clutter in his office he noticed a culture of staphylococcus in which a fungus was growing. The fungus had pushed back the staph in a characteristic ring of inhibition. As the story goes, he hypothesized that the fungus must be producing something that retarded bacterial growth. The fungus Penicillium notatum (http://en.wikipedia.org/wiki/Penicillium_notatum) produces a chemical now commonly known as penicillin, which caused a great leap forward in western medicine. The effect has been so great that the old killers of yesteryear, the terrible diseases that struck fear in the hearts of man for ages before are no longer thought of in the same grave tone and are considered more of a nuisance to public health, a mere trifle in consideration of the ‘far greater’ concerns of the populace. Perhaps the greatest triumph is the reaction of surprise that “people still get that?!”

Penicillin was originally isolated from cultures of Penicillium notatum*. It is a secondary metabolic product, released only when the fungi is under environmental stress. Early manufacture methods were hampered, because finding just the right conditions for growth and just the right strains proved difficult, thus production was initially low. It was so prized that during World War II doctors would collect their patient’s urine to isolate and reuse the excreted portion of penicillin. Today, it is manufactured in large tanks where conditions such as the pH, temperature and diet are all automatically controlled to elicit maximum output. The tanks are filled with a growth medium consisting of a source of carbon (lactose) and nitrogen for the fungi to feed upon. The incubating contents are constantly aerated to allow for maximum growth throughout the tank. I imagine it probably looks somewhat similar to a bubble tea with tapioca pearls of blue-green fungus floating in it. When the growth phase has completed the contents are filtered and the raw penicillin goes through various chemical preparations. There are many different kinds of penicillin, differing by the addition of a functional group to the backbone structure: the B-Lactam ring (http://en.wikipedia.org/wiki/Beta-lactam).

http://i131.photobucket.com/albums/p297/jubei33/penicillins.jpg

Each different preparation has different activities against many kinds of bacteria. Both gram negative and gram positive bacteria, staphylococci, streptococci and anaerobic bacteria all have representatives that are susceptible to these chemicals. Penicillin G, for example, is strongest against Gram positive organisms, gram negative cocci and non-B-lactamase producing bacteria (an enzyme that breaks the B-Lactam ring). Nafcillin is good against staphylococci and streptococci, but weak against enterococci and gram negative cocci and rods.

With such a wide range of activities against so many organisms one might wonder how they work. Simply put, they inhibit bacterial growth and the replacement of their cell walls, which causes them to die. Bacterial cell walls are composed of long chains of six carbon sugars with amino acid side chains that weave the chains together like a net. The long chains are made by polymerizing N-acetylglucosamine and N-acetlymuramic acid sugars into alternating units. The side chains are made of repeating amino acid units, which differ per species, but for susceptible species they end with the combination D-alanyl-D-alanine amino acids.

http://i131.photobucket.com/albums/p297/jubei33/bacterialcellwallchain.jpg

B-Lactam antibiotics are natural analogues of these amino acids, which is to say they can fit into some of the same places as the natural bacterial amino acid piece can. The antibiotics attach themselves to a special protein (the aptly named ‘penicillin binding protein’) that transports and tethers the D-alanyl-D-alanine amino acids to other chains in the cell wall. With the protein blocked it cannot transport new pieces of the wall for replacement and it leaves the cell unable to grow and more susceptible to lysis by making the cell wall to weak to withstand the osmotic pressure on it.

It is important to point out that these antibiotics are most active when bacteria are growing and synthesizing cell walls, which is fine for fast growing colonies. However, take for instance mycobacteria (http://en.wikipedia.org/wiki/Mycobacterium), which are most famous for causing tuberculosis and leprosy. These bacteria have a dormant state where they don’t synthesize a cell wall. In this context, an attack of this kind would be useless or at the very most a stop gap measure. In fact, these bacteria require a different approach to overcome them, especially considering that they are notorious for developing resistances to antibiotics and that their cell walls are different in that they contain certain fatty acids, which impede the entry of chemicals (especially true of B-Lactam antibiotics). Because of these factors, treatments for tuberculosis generally take upwards of a year or more to complete.

In a colony of 10^6 bacteria, the probability is that at least one will have resistance to a given antibiotic. A typical mycobacterial colony will have something around 10^8 members, making the probability of selection a problem. Once a group that has specific immunity has been selected, they can trade this information with other bacteria via plasmid exchange, thus creating strains able to resist ordinary actions against them. This is how bacteria such as the dreaded MRSA (http://en.wikipedia.org/wiki/Mrsa) have developed and become a problem. In this particular case, the problem is usually taken care of with multi-drug therapies, such that 95-98% of tuberculosis cases can be cured with an isonaizid-rifampin combination (which are not B-Lactam antibiotics btw). The probability that one will have a resistance against both antibiotics is very low and using two will usually kill the bacteria that have a selected immunity to one antibiotic alone.

Bacterial resistances usually present via four different routes: Reduced membrane permeability to the drug, production of an enzyme that deactivates the antibiotic (a B-lactamase, for example), a change in the receptor site where the antibiotic binds and finally, the creation of a means for drug removal. With penicillins, B-Lactamase production is the most common form of resistance, some of which are highly specific to only one kind of drug. Altered penicillin binding proteins generally will have a shape that is less able to fit the B-Lactam structure, or in chem-speak have less affinity for them. They are often times not blocked, but just less able to reach the concentration necessary to inhibit cell wall growth inhibition. Gram negative bacteria usually develop a resistance to antibiotic entry by changing the shape of (or removing them from use via down regulation) receptors that transport the antibiotic across its membrane. They also are known to make what is called an efflux pump, which transports the antibiotic back across the membrane after entry. Both of these methods are usually paired with a B-Lactamase enzyme.

All in all, penicillin is generally considered non-toxic. The worst adverse reactions are due to hypersensitivities. Allergic reactions occur, however, this is a rarity occurring in less than 1% of people and is usually not life threatening (a rash, fever, etc). Even less have a serious reaction, like anaphylactic shock (0.05% of patients). In a worst-case scenario, though, desensitization to the drug can be used to effectively treat a given disease.


*hmmm, apparently they gave it a new name because its so awesome: Penicillium chrysogenum

An interesting short history of the industrial process, etc:
http://botit.botany.wisc.edu/Toms_fungi/nov2003.html

WarPhalange
15th October 09, 10:00 AM
LOL @ she-ass.

Yeah, that's all I read, sorry. :(

Shotgun Christening
15th October 09, 11:36 AM
Im deathly allergic to penicillin. Or any "cillin" for that matter.
I dont give a fuck about the stuff.

resolve
15th October 09, 12:15 PM
Well other people taking it has prevented those diseases it takes care of from being spread to you...

I love reading stuff like this! +rep

Shotgun Christening
15th October 09, 12:26 PM
Well other people taking it has prevented those diseases it takes care of from being spread to you...

I love reading stuff like this! +rep


Like infections? I havent ever had an infection of any kind.....oh wait, yes I have.
Dont be a tard......Penicillin doesnt prevent disease in the way you are alluding to.. It cures infections. You dont get a fucking penicillin shot to keep you from getting a virus.

SFGOON
15th October 09, 01:08 PM
The real question is "H0w D0 1S0LATi0N?" From the mold, that is.

Just the broad strokes. My best n00b guess is acetone as a solvent and a vacuum filtering flask, but I can't tell by looking if penicillin is volatile or has a fucked up vapor pressure at STP.

resolve
15th October 09, 02:14 PM
Like infections? I havent ever had an infection of any kind.....oh wait, yes I have.
Dont be a tard......Penicillin doesnt prevent disease in the way you are alluding to.. It cures infections. You dont get a fucking penicillin shot to keep you from getting a virus.

Before your internet rage reaches a premium, you should step back and think of what I actually wrote, instead of strawmanning the shit out of me.

I was saying that by giving penicillin to members of a society who are not allergic to it, that stops the spread of disease to YOU from THEM.

Most infections/diseases you'll get will be transferred from one person to another and not directly from the environment to you. So by keeping a population healthy with penicillin/antibiotics keeping infection rates down overall it has an influence on you as well.

And yes, I realize that antibiotics don't work on virii...

resolve
15th October 09, 02:15 PM
The real question is "H0w D0 1S0LATi0N?" From the mold, that is.

Just the broad strokes. My best n00b guess is acetone as a solvent and a vacuum filtering flask, but I can't tell by looking if penicillin is volatile or has a fucked up vapor pressure at STP.


You were born in the wrong era. WTB time machine to send SFGoon back to the dark ages.

jubei33
15th October 09, 04:57 PM
Im deathly allergic to penicillin. Or any "cillin" for that matter.
I dont give a fuck about the stuff.
Really? In what illness was the reaction brought about and what kind of reaction did you have? Allergies to it are a relatively rare occurrence, I'm told.

did you know there is a broad basis of similarity to certain other classes of antibiotics, typically used if someone is allergic to penicillin?





My best n00b guess is acetone as a solvent and a vacuum filtering flask, but I can't tell by looking if penicillin is volatile or has a fucked up vapor pressure at STP.

You're lucky I found you time traveler:
Recovery of solid 6-aminopenicillanic acid (http://v3.espacenet.com/publicationDetails/biblio?CC=US&NR=2941995A&KC=A&FT=D&date=19600621&DB=EPODOC&locale=en_EP)

Usually you wouldn't want to just isolate the base product from the mother liquor, you'd want to try and eliminate extra steps (time is money). Adding phenylacetyl chloride yields benzyl penicillin just from the batch feed.

jubei33
15th October 09, 05:00 PM
Before your internet rage reaches a premium, you should step back and think of what I actually wrote, instead of strawmanning the shit out of me.

I was saying that by giving penicillin to members of a society who are not allergic to it, that stops the spread of disease to YOU from THEM.

Most infections/diseases you'll get will be transferred from one person to another and not directly from the environment to you. So by keeping a population healthy with penicillin/antibiotics keeping infection rates down overall it has an influence on you as well.

And yes, I realize that antibiotics don't work on virii...

This sounds suspiciously like socialized medicine or is it

A social impact of medicine?

jubei33
15th October 09, 05:42 PM
on a side note, does anyone know how to wrap text around the pictures?

Shotgun Christening
16th October 09, 06:09 AM
Before your internet rage reaches a premium, you should step back and think of what I actually wrote, instead of strawmanning the shit out of me.

Im not sure you know what a strawman is...



I was saying that by giving penicillin to members of a society who are not allergic to it, that stops the spread of disease to YOU from THEM.

Most infections/diseases you'll get will be transferred from one person to another and not directly from the environment to you. So by keeping a population healthy with penicillin/antibiotics keeping infection rates down overall it has an influence on you as well.

And yes, I realize that antibiotics don't work on virii...

Of course this all started when you took issue with me not giving a fuck about penecillin being invented.

SARCASM, you intertard. SARCASM. Look it up, look up strawman while you are at it.

Shotgun Christening
16th October 09, 06:14 AM
Really? In what illness was the reaction brought about and what kind of reaction did you have? Allergies to it are a relatively rare occurrence, I'm told.


I was 12 and took them for a lung infection. I had taken penecillin before, but this time it made my joints swell up and get protruding knots on them and closed my airway off within 5 minutes of taking it.
They ran tests and found out that I was allergic to it. Soemthing about what they are made of in particular.
I have severe mold and fungus allergies.



did you know there is a broad basis of similarity to certain other classes of antibiotics, typically used if someone is allergic to penicillin?

Oh, I know...I take Zithromax and Levaquin when I need antibiotics. For some reason these dont have the same make up as "cillins"
I cant even give it to my kids, or handle the pills. We have some in our house now but it is kept safely away from my meds.

BTW, I was using sarcasm in my "dont give a fuck" post.

bob
16th October 09, 06:23 AM
My son had scarlet fever this week. "Scarlet Fever?!" sez I. "That's the shit that kills people in old timey movies, no?"
"Yes, but not since they developed penicillin."

Word.

socratic
16th October 09, 06:52 AM
My son had scarlet fever this week. "Scarlet Fever?!" sez I. "That's the shit that kills people in old timey movies, no?"
"Yes, but not since they developed penicillin."

Word.

Antibiotics also ended the tyrannical reign of syphillis.

At least in developed countries.

jubei33
16th October 09, 04:34 PM
I was 12 and took them for a lung infection. I had taken penecillin before, but this time it made my joints swell up and get protruding knots on them and closed my airway off within 5 minutes of taking it.
They ran tests and found out that I was allergic to it. Soemthing about what they are made of in particular.
I have severe mold and fungus allergies.

Oh, I know...I take Zithromax and Levaquin when I need antibiotics. For some reason these dont have the same make up as "cillins"
I cant even give it to my kids, or handle the pills. We have some in our house now but it is kept safely away from my meds.

BTW, I was using sarcasm in my "dont give a fuck" post.

Interesting, Thanks for sharing. You're pretty lucky. :redface:

yeah zithromax is a macrolide antibiotic, very popular and useful. Others in the group are eurythromycin and clairithromycin (etc), which all work by blocking bacterial protein synthesis rather than affecting cell wall growth like B-lactams. They cock block the bacterial ribosome from getting its amino acid chain up.
Levaquin is a fluoroquinolone, in the same class of drugs as the now famous cipro (during the anthrax scares). It stops Bacterial DNA form being unwound during replication, but not only that they have serious warnings for humans as well.


"dont give a fuck"
This R seRious thread ;)

jubei33
16th October 09, 04:35 PM
My son had scarlet fever this week. "Scarlet Fever?!" sez I. "That's the shit that kills people in old timey movies, no?"
"Yes, but not since they developed penicillin."

Word.

RESPECT YO! fist bump

she doing all right?

Shotgun Christening
16th October 09, 04:47 PM
Interesting, Thanks for sharing. You're pretty lucky. :redface:

yeah zithromax is a macrolide antibiotic, very popular and useful. Others in the group are eurythromycin and clairithromycin (etc), which all work by blocking bacterial protein synthesis rather than affecting cell wall growth like B-lactams. They cock block the bacterial ribosome from getting its amino acid chain up.
Levaquin is a fluoroquinolone, in the same class of drugs as the now famous cipro (during the anthrax scares). It stops Bacterial DNA form being unwound during replication, but not only that they have serious warnings for humans as well.

Wow....you do love medicine...
:)



This R seRious thread ;)

eye yam surree eye wunt do eet a gayun.

bob
16th October 09, 07:37 PM
RESPECT YO! fist bump

she doing all right?

He was basically fine with 24 hours of his first dose. That shit works faster than fiber.

resolve
17th October 09, 12:11 AM
SARCASM, you intertard. SARCASM. Look it up, look up strawman while you are at it.


Sarcasm? When you neg repped me for "not knowing what penicillin is for bacteria not viruses!" when I stated specifically the opposite fact? That must be a new breed of sarcasm I've not heard about. I hope it isn't one of those new super-sarcasms that are antibiotic resistant!

Strawman is when you set up an argument similar but not the same as your debate opponents and then attack that instead of their actual argument.

It is what you did and are actually still continuing to do.

But, whatev, I didn't attack you for not caring, I attacked you for not understanding. Big difference. I really don't know why you are continuing this. Trying to salvage some lost pride on the internet? I lose pride every time I post in sociocide, you don't see me whining like a little bitch about it!

Shotgun Christening
17th October 09, 06:25 AM
Sarcasm? When you neg repped me for "not knowing what penicillin is for bacteria not viruses!" when I stated specifically the opposite fact? That must be a new breed of sarcasm I've not heard about. I hope it isn't one of those new super-sarcasms that are antibiotic resistant!

Boo Hoo....a red varrot. If it will make you feel better you can give me one too.



Strawman is when you set up an argument similar but not the same as your debate opponents and then attack that instead of their actual argument.

It is what you did and are actually still continuing to do.

Ummmm....I didnt start any type of argument. I made a comment that I didnt care....YOU missed the sarcasm in my OP and chided me on how great they were.
Seek help.....really.....seek it.



But, whatev, I didn't attack you for not caring, I attacked you for not understanding. Big difference. I really don't know why you are continuing this. Trying to salvage some lost pride on the internet? I lose pride every time I post in sociocide, you don't see me whining like a little bitch about it!

Just a few points...

1) I think by continuing to post replies to my replies that you are the one "keeping this going". I didnt start anything. I made a comment that was sarcastic, you missed it, and now you think I dont understand your point. I understand it perfectly fine...I just dont care.

2) LOL at the "salvaging pride" comment.....really?


When you neg repped me

HAHAHAHAHAHAHAHAHA.......


Listen....you missed my sarcasm. I was having fun with you by watching you rile up over something as trivial as this. Its easy.
I KNEW that..

a) a neg rep would rile you up
b) me throwing out a strawman would rile you up (which I freely admit I did)
c) That me accusing you of throwing out a strawman (after my blatant tossing up of one) would rile you up.

Lets look at it this way.
Say someone threw out a post about how great car tires where. Then I responded by saying "car tires suck. I hate them"
Would you take the time to tell me how the use of car tires makes my life better? I would hope not since you should know or at least have the suspicion that I was being sarcastic.