Since the dawn of Penicillin, bugs have been finding ways to combat our antibiotics. Why? Natural selection. Every time a species reproduces, the next generation will have some kind of mutation – a change in the genetic structure that preceded it. Sometimes these are bad mutations – and those members of the population die off. Sometimes, however, these mutations allow the species to live longer and survive more obstacles. Think of that bug in the forest that looks like a leaf. His species used to probably look like any other bug. However, one day, a gene mutation arose, allowing him to look like a leaf. Blending in with his environment thus so, birds and other creatures were less likely to eat him, so he survived and kept that gene.
Now, with things like woodland creatures, or human beings, etc. these mutations take time. Evolution, in general, takes time… for most life forms. Bacteria, on the contrary, reproduce rapidly. Add that to the fact that they can and will eventually harbor a gene that could combat antibiotics, and you’ve got a scary bad situation on your hands.
MRSA is among these bacteria. You’ve heard of this one before. It’s a bacterial species that has come about due to a gene mutation that created an entirely new species of S. Aureus bacteria. It resists our strongest antibiotics, it’s extremely dangerous, etc.
NDM1 (aka Beta Lactamase), on the other hand, is not a bacteria itself, but an enzyme; However, it does come about because of that same “favorable mutation” situation discussed above. The actual acronym stands for New Dehli (where it originated) Metallo Beta Lactamase (enzyme that cuts beta lactam). Any protein ending with “-ase”, is an enzyme. This enzyme is dangerous because it cuts up the key ingredient in the antibiotics which normally keep us safe (the beta lactam ring)
This is more of a danger, b/c this gene mutation can occur in any number of bacteria (usually gram negative), meaning that plenty of *different* types of bacteria can come to make this dangerous enzyme, not just one species. People tend to think of gram negative bacteria as being a bit more benign than gram positive bacteria. However, b/c of a phenomenon called “horizontal gene transfer”, bacteria can pass this mutation on to one another – including onto gram positive bacteria! (Note that gram positive and negative bacteria merely refers to their outer coat… g+ bacteria like Staphylococcus Aureus are usually thought to be more dangerous).
The picture below is a cartoon depiction I created to try and simplify the process that seems to be eluding many. Obviously, the molecular processes and pathogenesis is much more complicated, but this is the best way I can try to portray it for those without a bio background:
In other words:
NDM1 = Beta Lactamase Enzyme = Bad guy b/c it cuts the Beta Lactam Ring that make our antibiotics work.
Beta Lactam Ring = Good guy = key player within the antibiotics that fight against bacteria.
Reminder – how does this happen and why? It’s a favorable (for the bacteria) gene mutation.
The new NDM1 gene is what lets them make the NDM1 enzyme which then prevents antibiotics from killing them.
Upon further investigation, I “wikipedia’d” to read more, and noticed this gem (if you can’t read it, click on it. I can’t get it to fit the page):
Translated: The Beta Lactamase enzyme that is causing such a problem can be hindered. This excerpt is telling us that Clavulanic Acid has the capability of binding the enzyme irreversibly, before said enzyme can cleave our antibiotic’s Beta Lactam ring … voila! With the Beta Lactamase enzyme bound, the B.Lac rings are free from danger, so the antibiotics can do their job again~!! So does this mean that Clavulanic Acid is the answer to all our fears w/regard to NDM1? My guess is the obvious: It’s just a matter of time before C.Acid has Darwin’s natural selection in its crosshairs too, and bacteria evolve to evade it… somehow. A scientist who works in this field has the job of simply chasing their own tails; no sooner do they create the antibiotic before the bacteria find a way to fight back. Then, it’s back to the lab to find a new plan of attack.
Til then, I hope this little piece shed some light on NDM1 -not a bacteria – but an enzyme; An enzyme some bacteria have “learned” to make to avoid our antibiotics, thanks to a favorable (for them) gene mutation…
xoxo
<3~A
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I am quite sure that clavulanic acid does not inhibit metallo-beta-lactamases like NDM-1. This is why there is nothing against NDM-1 at the moment. Besides, clavulanic acid is an old compound and much better beta-lactamase inhibitors have been developed since the days of clavulanic acid. Unfortunately, NDM-1 resists all of them.
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