Syphilis and penicillin

[Doc187]

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Can someone explain why penicillin is the treatment of choice for syphilis, given that Treponema pallidum pallidum is Gram negative?

 

[Raryn]

Can someone explain why penicillin is the treatment of choice for syphilis, given that Treponema pallidum pallidum is Gram negative?

Because it works.

 

[Dr McSexy]

 

[Doc187]

It's okay. I don't know either. Maybe we can all learn something if someone more knowledgable would like to share.

 

[Bacchus]

Google: treponema pallidum penicillin first response: http://www.clinicalcorrelations.org/?p=1657

Here's more about the Tp protein: http://www.pnas.org/content/91/24/11611.full.pdf

 

[Raryn]

It's okay. I don't know either. Maybe we can all learn something if someone more knowledgable would like to share.

While most penicillin sensitive organisms are gram positive, some gram negatives are penicillin sensitive as well. Pretty much the same mechanism, though it doesn't as !@#$ up their cell walls quite as thoroughly as it does for the gram-positive ones.

Think of how many other beta-lactam antibiotics are effective against a wide range of gram negatives?

But really, the answer is the same as the one I gave above. It's used because it works.

 

[CoolWhipp]

http://www.clinicalcorrelations.org/?p=1657

"Tp47 [protein made by the bacterium] functions as both a PBP [penicillin binding protein] and a beta lactamase. However, it may paradoxically be responsible for the persistence of PCN sensitivity in syphilis. The binding of the beta lactam component of PCN to Tp47 results in hydrolysis of the beta-lactam bond of the antibiotic. However, in the process of this reaction several byproducts are created. The thought is that these byproducts have a higher affinity for Tp47 than the beta lactam itself[9]. Thus as a consequence of PCN being broken down, products are released which make it more difficult for the beta-lactamase to bind the antibiotic."

 

[ijn]

The only bacteria which penicillin has absolutely no effect are those without peptidoglycan cell walls (ex. mycoplasma, chlamydia, etc.). Penicillins might not work as well if you have PBP mutations or beta lactamases, but that's not a property exclusive to gram negatives. Since gram negatives need a cell wall to survive inhibiting the synthesis of its cell wall will have a bactericidal effect.

As for why it's the drug of choice, "it works" is about as good of an explanation as you're going to get. Pencillin is cheap and clearly if it's still the drug of choice in 2012 then treponema doesn't have the capacity to develop significant resistance to it.

 

[Bacchus]

http://www.clinicalcorrelations.org/?p=1657

"Tp47 [protein made by the bacterium] functions as both a PBP [penicillin binding protein] and a beta lactamase. However, it may paradoxically be responsible for the persistence of PCN sensitivity in syphilis. The binding of the beta lactam component of PCN to Tp47 results in hydrolysis of the beta-lactam bond of the antibiotic. However, in the process of this reaction several byproducts are created. The thought is that these byproducts have a higher affinity for Tp47 than the beta lactam itself[9]. Thus as a consequence of PCN being broken down, products are released which make it more difficult for the beta-lactamase to bind the antibiotic."

So good, you had to repost it a second time 😉.

 

[pkwraith]

Penicillin doesn't work on most gram-negatives because they typically have good beta-penicillinases and other mechanisms like limited porin sizes.

Treponema is extremely fragile and doesn't have a lot of antibiotic resistance. A butload of antibiotics will work on it, but penicillin is cheap with not a lot of side effects.

 

[Carboxide]

Can someone explain why penicillin is the treatment of choice for syphilis, given that Treponema pallidum pallidum is Gram negative?

Good question. Usually pen G is only G+ active, NOT because of B-lactamase activity but because it's a highly lipophilic molecule that must partition through the membrane. G- cells are usually attacked via porin entry, requiring a hydrophilic molecule - which is why we modify them (see: Pen V vs Pen G) to increase spectrum. There's not a whole lot out there on why Pen G is active against syphilis, but I suspect it's because of the unusual cell wall - it contains very few proteins, unlike most cell walls. I think it must partition through more easily than in other cells. That's just an idea, though.

 

[Carboxide]

Penicillin doesn't work on most gram-negatives because they typically have good beta-penicillinases and other mechanisms like limited porin sizes.

Wrong. Penicillin don't work on G-s because they can't get through the porin, because they're too lipophilic. Resistance has nothin' to do with it, nor does porin size. You can get huge ****ing molecules through porins - WAY bigger than cillins. Check out some of the cephalosporins out there. They're double the size.

 

[Carboxide]

The only bacteria which penicillin has absolutely no effect are those without peptidoglycan cell walls (ex. mycoplasma, chlamydia, etc.). Penicillins might not work as well if you have PBP mutations or beta lactamases, but that's not a property exclusive to gram negatives. Since gram negatives need a cell wall to survive inhibiting the synthesis of its cell wall will have a bactericidal effect.

As for why it's the drug of choice, "it works" is about as good of an explanation as you're going to get. Pencillin is cheap and clearly if it's still the drug of choice in 2012 then treponema doesn't have the capacity to develop significant resistance to it.

Mycoplasma and chlamydia both have cell walls made of peptidoglycan...chlamydia is a typical G-. Myco is not susceptible because its genome codes for B-lactamase. Other cell wall synth inhibitors (like isoniazid) work on it just fine.

What are they TEACHING you guys??

 

[Bacchus]

Mycoplasma and chlamydia both have cell walls made of peptidoglycan...chlamydia is a typical G-. Myco is not susceptible because its genome codes for B-lactamase. Other cell wall synth inhibitors (like isoniazid) work on it just fine.

What are they TEACHING you guys??

Not the MOA of penicillin on syphilis. That's for you to know. What you get semesters of we get lectures of. I had 2 lectures on pharmacokinetics. That's 2 hours. You have much, much more.

 

[tiedyeddog]

Mycoplasma and chlamydia both have cell walls made of peptidoglycan...chlamydia is a typical G-. Myco is not susceptible because its genome codes for B-lactamase. Other cell wall synth inhibitors (like isoniazid) work on it just fine.

What are they TEACHING you guys??

Dude, mycoplasma do not have any peptidoglycan's in their outer membrane. That's the major reason they are so incredibly small.... http://www.hhmi.org/biointeractive/Antibiotics_Attack/bb_3.html
http://en.wikipedia.org/wiki/Bacterial_cell_structure

They lack cell walls. B-Lactam and their derivatives (cephalosporins, Carbapenems, Aztreonam, etc, ) have zero effect because they don't need a transpeptidase (normally penicillin binding protein.)

Chylamadia is also lacking peptidoglycans. They have a cell wall, made out of something similar in function to peptidoglycans and it is thought they still need a transpeptidase, similar to PBP so PCN works in Chylamadia infections.
http://www.ncbi.nlm.nih.gov/pubmed/8162358
http://microbewiki.kenyon.edu/index.php/Chlamydia

Could you go back to the pharmacy forums? We're having a serious conversation here, let the adults talk. 😎

(P.S. mycobacteria and mycoplasma are two different genuses. Isoniazid is for TB or Leprosy, not Mycoplasma. Isoniazid only works on bacteria that use mycolic acid, which does not include Chlamydia.... http://en.wikipedia.org/wiki/Isoniazid#Mechanism_of_action)

 

[turkeyjerky]

Dude, mycoplasma do not have any peptidoglycan's in their outer membrane. That's the major reason they are so incredibly small.... http://www.hhmi.org/biointeractive/Antibiotics_Attack/bb_3.html
http://en.wikipedia.org/wiki/Bacterial_cell_structure

They lack cell walls. B-Lactam and their derivatives (cephalosporins, Carbapenems, Aztreonam, etc, ) have zero effect because they don't need a transpeptidase (normally penicillin binding protein.)

Chylamadia is also lacking peptidoglycans. They have a cell wall, made out of something similar in function to peptidoglycans and it is thought they still need a transpeptidase, similar to PBP so PCN works in Chylamadia infections.
http://www.ncbi.nlm.nih.gov/pubmed/8162358
http://microbewiki.kenyon.edu/index.php/Chlamydia

Could you go back to the pharmacy forums? We're having a serious conversation here, let the adults talk. 😎

(P.S. mycobacteria and mycoplasma are two different genuses. Isoniazid is for TB or Leprosy, not Mycoplasma. Isoniazid only works on bacteria that use mycolic acid, which does not include Chlamydia.... http://en.wikipedia.org/wiki/Isoniazid#Mechanism_of_action)

Pwnage!

Also, the difference between Pen V and Pen G is that Pen V is orally available, not that it's got a better spectrum of activity (it's actually less active against gram negatives than pen G).

What do they teach you guys in pharmacy school?

 

[ArcGurren]

Mycoplasma and chlamydia both have cell walls made of peptidoglycan...chlamydia is a typical G-. Myco is not susceptible because its genome codes for B-lactamase. Other cell wall synth inhibitors (like isoniazid) work on it just fine.

What are they TEACHING you guys??

Um, no. Mycoplasma has NO cell wall.

Pen G is used for syphillis because (a) it works incredibly well and (b) it's one of the last few bugs that really gets slaughtered by penicillin. As long as it still works we dont have to worry about resistance

 

[Raryn]

Dude, mycoplasma do not have any peptidoglycan's in their outer membrane. That's the major reason they are so incredibly small.... http://www.hhmi.org/biointeractive/Antibiotics_Attack/bb_3.html
http://en.wikipedia.org/wiki/Bacterial_cell_structure

They lack cell walls. B-Lactam and their derivatives (cephalosporins, Carbapenems, Aztreonam, etc, ) have zero effect because they don't need a transpeptidase (normally penicillin binding protein.)

Chylamadia is also lacking peptidoglycans. They have a cell wall, made out of something similar in function to peptidoglycans and it is thought they still need a transpeptidase, similar to PBP so PCN works in Chylamadia infections.
http://www.ncbi.nlm.nih.gov/pubmed/8162358
http://microbewiki.kenyon.edu/index.php/Chlamydia

Could you go back to the pharmacy forums? We're having a serious conversation here, let the adults talk. 😎

(P.S. mycobacteria and mycoplasma are two different genuses. Isoniazid is for TB or Leprosy, not Mycoplasma. Isoniazid only works on bacteria that use mycolic acid, which does not include Chlamydia.... http://en.wikipedia.org/wiki/Isoniazid#Mechanism_of_action)

👍

 

[tiedyeddog]

👍

You know, my life sucks when the brightest point of my day is disgracing some random pharm student on the interwebz.... I hate test week.

 

[Carboxide]

Dude, mycoplasma do not have any peptidoglycan's in their outer membrane. That's the major reason they are so incredibly small.... http://www.hhmi.org/biointeractive/Antibiotics_Attack/bb_3.html
http://en.wikipedia.org/wiki/Bacterial_cell_structure

They lack cell walls. B-Lactam and their derivatives (cephalosporins, Carbapenems, Aztreonam, etc, ) have zero effect because they don't need a transpeptidase (normally penicillin binding protein.)

Chylamadia is also lacking peptidoglycans. They have a cell wall, made out of something similar in function to peptidoglycans and it is thought they still need a transpeptidase, similar to PBP so PCN works in Chylamadia infections.
http://www.ncbi.nlm.nih.gov/pubmed/8162358
http://microbewiki.kenyon.edu/index.php/Chlamydia

Could you go back to the pharmacy forums? We're having a serious conversation here, let the adults talk. 😎

(P.S. mycobacteria and mycoplasma are two different genuses. Isoniazid is for TB or Leprosy, not Mycoplasma. Isoniazid only works on bacteria that use mycolic acid, which does not include Chlamydia.... http://en.wikipedia.org/wiki/Isoniazid#Mechanism_of_action)

Hah. You're right, I mixed up mycoplasma and mycobacterium. +1 for you.

As for chlamydia: that is not certain. Certain papers published
http://www.sciencedirect.com/science/article/pii/S0966842X05003355
have shown that they do have a complete and functioning PG pathway that is activated during division.

Pwnage!

Also, the difference between Pen V and Pen G is that Pen V is orally available, not that it's got a better spectrum of activity (it's actually less active against gram negatives than pen G).

What do they teach you guys in pharmacy school?

That is ONE difference. However, Pen V is much more G- active. Check out the structures...it's all there. In fact, it's the same substitution that changes both factors: the phenoxy vs benzyl. Pen G is so lipophilic it has almost no G- activity; the ester in Pen V greatly increases it. In the same way, the only reason Pen V is orally active (and to be fair, Pen G is about 15% absorbed) is that the oxygen prevents the acid instability that causes stomach deactivation. It does act on a very few, very specific G- bac (syphilis, gonorrhea, H. influenzae) but that's about. it.

Pen V has less activity overall; this is why it's used less, not because its spectrum is lesser. Check out Foye's Medicinal Chemistry if you want more info.

 

[Mattchiavelli]

It's because you can give a giant slug of Pen G in the gluteus and be pretty confident it's going to clear the patient, or you can give them a script for Pen V which they will maybe take to completion and maybe not cause their next partner to get syphilis

 

[CoolWhipp]

So good, you had to repost it a second time 😉.

I admit I didn't read the replies, but it was good.

 

[Untraditional]

This thread should be locked or pruned because of the enormous amounts of bad / wrong information.

 

[turkeyjerky]

This thread should be locked or pruned because of the enormous amounts of bad / wrong information.

Perhaps you should correct some of the inaccuracies, rather than just labeling it "bad".

At the very least, this thread should give pause to those who would take the musings of PharmD's as the gospel during rounds...

 

[Untraditional]

Perhaps you should correct some of the inaccuracies, rather than just labeling it "bad".

At the very least, this thread should give pause to those who would take the musings of PharmD's as the gospel during rounds...

Others already have and it has just precipitated into an arugment.