How Does Ampiox Work Against Bacteria?

[Eagle9]

Citation:

Ampiox is a broad-spectrum antibiotic that contains two active ingredients: Ampicillin and Oxacillin. Ampicillin and Ampiox belong to a group of preparations called penicillin antibiotics. Ampicillin and Ampiox interferes with the ability of the bacteria to form cell walls. Bacterial cell walls protect cells from entering the foreign substances inside the cells and stop the contents of cells from leaking out. Ampicillin and Ampiox work by inhibiting enzyme transpeptidase, disturbing the synthesis of peptidoglycane that is essential component in bacterial cell walls. This causes hole to appear in the bacterial cell walls resulting in lysis of the bacteria. Ampiox is effective against wide variety of Gram-positive and Gram-negative bacteria.

http://www.igenericdrugs.com/?s=Ampiox
So, the Ampiox suppress the synthesis of peptidoglycane that are absolutely necessary for cell walls, also it inhibits the enzyme called transpeptidase that “cross-links peptidoglycan chains to form rigid cell walls” (http://en.wikipedia.org/wiki/DD-transpeptidase ) and all these action leads to bacterial lysis. This is clear, but imagine some certain (one) bacterium that already has got both transpeptidase and peptidoglycanes in its cell wall in a necessary amount and therefore this bacterium does not need any additional transpeptidase and/or peptidoglycanes. The question: can Ampiox cause lysis of this bacterium? If transpeptidase and/or peptidoglycanes are degraded (http://en.wikipedia.org/wiki/Protein_degradation ) from time to time (because of various reasons) then they need to be synthesized and replaced by new molecules. If so, then I can understand why Ampiox causes lysis: old transpeptidase and peptidoglycanes molecules are degraded, new ones cannot be created and the bacteria die.

But if both transpeptidase and peptidoglycanes are relatively long-live then Ampiox cannot cause the lysis, at least Ampiox cannot destroy the already-existing bacteria. As for newly created bacteria (after/during Cell division) that are growing and probably need more and more transpeptidase and peptidoglycanes they (bacteria) can be subjected to Ampiox action.

So, could you please tell me how exactly Ampiox act on bacteria?

 

[Yanick]

This may help you.

 

[Ygggdrasil]

You hit on a very important point: in order for most antibiotic drugs to kill bacteria, the bacteria must be actively growing and metabolizing. This point is important because many bacterial populations include a small subset of dormant cells which are not killed by antibiotic treatment. We call these cells that escape treatment persisters. These persisters are not resistant – if you let the persister population re-expand then treat with antibiotics, you will kill still kill most of the population and leave a similar fraction of persister cells – but rather they tolerate antibiotic treatment because they are metabolically dormant.

 

[Eagle9]

This may help you.

Let’s see:

Gram-negative bacteria such as Escherichia coli break down and reuse over 60% of the peptidoglycan of their side wall each generation.
Recycling of newly made peptidoglycan during septum synthesis occurs at an even faster rate.
Nine enzymes, one permease, and one periplasmic binding protein in E. coli that appear to have as their sole function the recovery of degradation products from peptidoglycan, thereby making them available for the cell to resynthesize more peptidoglycan or to use as an energy source, have been identified. It is shown that all of the amino acids and amino sugars of peptidoglycan are recycled
In addition, the possible role of various peptidoglycan degradation products in the induction of β-lactamase is discussed.

So, generally the peptidoglycans are degraded and then they are regenerated newly. Actually this is what I wanted to know, thanks

Ygggdrasil

You hit on a very important point: in order for most antibiotic drugs to kill bacteria, the bacteria must be actively growing and metabolizing.

Well, now I am earning my Master’s degree and my thesis is about action mechanism of various antibiotics on bacterial proliferation. Exactly during proliferation we observe antibiotic’s action. However, sometimes we add antibiotic BEFORE beginning of bacterial proliferation.

This point is important because many bacterial populations include a small subset of dormant cells which are not killed by antibiotic treatment.

Yes, not all bacteria are killed by antibiotics.

We call these cells that escape treatment persisters.

Well, I did not know if they had a special name.

These persisters are not resistant – if you let the persister population re-expand then treat with antibiotics, you will kill still kill most of the population and leave a similar fraction of persister cells – but rather they tolerate antibiotic treatment because they are metabolically dormant.

Very true! We observed the same result.
But could you please tell me what exactly means “metabolically dormant”? Are they dead? Are there biochemical reactions occurring?

 

[Ygggdrasil]

But could you please tell me what exactly means “metabolically dormant”? Are they dead? Are there biochemical reactions occurring?

You may find the following review articles helpful:

http://www.annualreviews.org/doi/abs/10.1146/annurev.micro.112408.134306
http://www.sciencedirect.com/science/article/pii/S0092867414002979

 

[Eagle9]

Ygggdrasil
Thanks