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A genetically modified bacterium that outcompetes bacteria causing tooth decay

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Re: A genetically modified bacterium that outcompetes bacteria causing tooth decay

#31
post #29

Earlier quoted context omitted.

A part of the story that has always made the claim more plausible to me is the claim that apes tend not to get cavities at the same rate we do. Since they have teeth that are as susceptible to acid as ours the story goes their diet tends to lead to other populations of bacteria in their mouthes out competing the cavity causing ones. Then people will go on to say that this ecosystem of mouth bacteria have co-evolved.…

The idea that primates get cavities less frequently than modern humans is a bit outdated and not terribly supported by recent studies. The main difference is in the location of the cavities, not frequency – apes tend to get cavities in their front teeth, humans tend to get cavities in the molars.

Oh interesting. I didn't realize. Are there theories on what causes that difference? Is it diet?

Re: A genetically modified bacterium that outcompetes bacteria causing tooth decay

#32
I'd want to know a lot more about that antibiotic these bacteria produce. If there is no natural immunity it will be developed very shortly if doses produced are low (and how can they possibly control for the dose). Then on the other hand if doses are really high, what about consuming an antibiotic for the rest of your life? What will it do to your gut flora?

It seems very implausible to me.

If I was working for FDA and someone was trying to bring such an obviously flawed product to the market I too would've asked them for very robust testing.

Re: A genetically modified bacterium that outcompetes bacteria causing tooth decay

#33
> They offered my wife and me free samples (based on her work, not as compensation for writing this post); she accepted, and I’m still debating.

Given that it's an oral colonist it seems likely that the author has tried the free sample as well, even if they were to live in a no-kissing houshold.

The title is a lovely garden path sentence: "A genetically modified bacterium that outcompetes bacteria causing tooth decay" -- a straightforward parse leads you to the plausible assumption that the genetically modified bacterium causes tooth decay. The insertion of a "the" before "bacteria" would remove the ambiguity.

Re: A genetically modified bacterium that outcompetes bacteria causing tooth decay

#34
post #3

Earlier quoted context omitted.

Somehow I keep loosing confidence in the FDA. That basically sounds like a special interest group giving unreasonable requirements to prevent it succeeding. What’s the chance that some of the FDA personnel were linked to companies in dental or dental care products? Perhaps some national association of dentists?

[flagged]

Yes, but Not the People.

Re: A genetically modified bacterium that outcompetes bacteria causing tooth decay

#36

Earlier quoted context omitted.

Your first point seems wrong. > cannot be true unless this strain is also capable of creating and tolerating environments with low pH Whether it can tolerate low pH environments is not particularly related to whether it creates low pH environments. If it's agnostic to pH levels around that range, then it can inhabit that niche whether or not there is acid being secreted.

I should clarify: there’s some more details to why S mutans actually requires low pH. The correct term wouldn’t be “tolerate low pH” but rather “requires low pH” for its stable colonization. S mutans creates incipient lesions by making acid, incipient lesions are micro environments where the low pH that causes enamel decay is determined by the biofilm on its surface. S mutans cannot thrive in environments with neutra…

The article gives this as the explanation of how it is supposed to work:

  BCS3-LI has four main genetic modifications:

  It produces a weak antibiotic, mutacin-1140, which kills competing oral bacteria.
  It’s immune to mutacin-1140, so it doesn’t kill itself.
  It metabolizes sugar through a different chemical pathway that ends in alcohol instead of lactic acid.
  It lacks a peptide that its species usually uses to arrange gene transfers with other bacteria.

  The antibiotic helps it win the Darwinian competition in your mouth to become King Of The Oral Bacteria. The alcohol metabolism means it won’t produce lactic acid (and so won’t cause tooth decay). The peptide knockout prevents it from transferring genes back and forth with other bacteria that might either inactivate it or leak its advantage.

Re: A genetically modified bacterium that outcompetes bacteria causing tooth decay

#37

Earlier quoted context omitted.

I should clarify: there’s some more details to why S mutans actually requires low pH. The correct term wouldn’t be “tolerate low pH” but rather “requires low pH” for its stable colonization. S mutans creates incipient lesions by making acid, incipient lesions are micro environments where the low pH that causes enamel decay is determined by the biofilm on its surface. S mutans cannot thrive in environments with neutra…

So to be specific what you're skeptical of here is that S. mutans can outcompete other bacteria without its ability to generate acid If this engineered version can stay in the mouth it should be able to live in the exact same lesions the non mutated version can right? It should still have all the adaptations to live in a low pH environment. I guess this is an extraordinary claim so it's right to be more cautious than…

Also keep in mind that this strain was discovered about 50 years ago in a human host (the "grad student" reference). The tech is in mutating it further to prevent adaptation, but the beneficial mutation (secretion of mutacin-1140) appears to be the product of natural evolution.

Re: A genetically modified bacterium that outcompetes bacteria causing tooth decay

#39

This story has been around for far too long and evidence is unbelievably weak, and the claims border on fraudulent. 1. The claim that this strain outcompetes the same S mutans from occupying the same niche cannot be true unless this strain is also capable of creating and tolerating environments with low pH. By definition if it creates acid to the same degree it will also cause cavities. 2. Single applications are ins…

From the article, the claim is that this strain of S mutans variant produces mutacin-1140 which allows it to outcompete other strains of S mutans and other Gram-positive bacteria.

I have no particular opinion about whether this claim is plausible or true, but you don't address this at all in your comment even though it's directly relevant.

For example, if this strain's production of mutacin-1140 allows it to kill other bacteria locally then it could maintain a niche despite higher pH. One way to view this is bacteriocin production substituting for lactic acid production as a weapon against competing bacteria.

Also, the percentage of the novel S mutans strain colonization is being measured in the first chart and shows initial 90%+ followed by a later drop and stabilization. It would be helpful to more directly address the evidence as presented.

EDIT: Also, this S mutans strain doesn't need to outcompete the entire existing oral microbiome. Even if mutacin-1140 is less effective than lactic acid at creating a niche, it suffices to just maintain a toehold in the microbiome while outcompeting existing acid-producing S mutans strains.

Re: A genetically modified bacterium that outcompetes bacteria causing tooth decay

#40

Earlier quoted context omitted.

So to be specific what you're skeptical of here is that S. mutans can outcompete other bacteria without its ability to generate acid If this engineered version can stay in the mouth it should be able to live in the exact same lesions the non mutated version can right? It should still have all the adaptations to live in a low pH environment. I guess this is an extraordinary claim so it's right to be more cautious than…

Also keep in mind that this strain was discovered about 50 years ago in a human host (the "grad student" reference). The tech is in mutating it further to prevent adaptation, but the beneficial mutation (secretion of mutacin-1140) appears to be the product of natural evolution.

The beneficial mutation is not secretion of mutacin-1140, but absence of lactic acid production. Transplanting only the original mutacin-1140-producing strain wouldn't help anyone, since it still produces lactic acid that would destroy your teeth all the same.

david_l_lin upthread is stressing that lactic acid is ordinary Streptococcus mutans' primary defense against other bacteria and it wouldn't be able to survive without it.

The significance of mutacin-1140 is that it provides an alternative means of defense against other bacteria (or maybe offense would be a better word) which potentially makes lactic acid redundant.

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