[david_l_lin]

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 neutral or high pH. the existing community (including other Streptococcus species) create local alkaline environment via multiple metabolic pathways, including the most well studied and prevalent arginine deiminase system. A “normal” healthy community antagonizes S mutans by maintaining a normal pH in saliva and the tooth surface, preventing stable colonization by S mutans.

Without acid production, S mutans cannot stably colonize. and is readily outcompeted by the existing community. Any novel strains of S mutans to “compete for the same niche” will suffer the same weakness unless they create acid. but if this “probiotic” also creates acid, then by definition it also causes cavities.

edit: adding citation https://www.futuremedicine.com/doi/10.2217/fmb-2018-0043

[Natsu]

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.

[Retric]

> It produces a weak antibiotic, mutacin-1140, which kills competing oral bacteria.

That alone isn’t enough for long term colonization as it’s not the only bacteria resistant to mutacin-1140.

[Natsu]

There's also a graph claiming to show colonization results. I don't know how good it is, but it's supposedly actual experimental data.

[extraduder_ire]

> It metabolizes sugar through a different chemical pathway that ends in alcohol instead of lactic acid.

It'd be quite funny to live in a future where cavities don't exist, but breathalysers are useless. (without rinsing your mouth out first, I guess) Hopefully it doesn't dry out gums and cause gum disease.

[MostlyStable]

The article extensively talks about the amount produced. While it has not been tested against breathalyzers, it is producing so little alcohol that it seems unlikely to be a problem. The claim in the article is that, across 24 hours, you might consume a few miligrams of alcohol, as compared to "if you swallowed 1/10th of your mouthwash, that would be ~200 milligrams of alcohol". So across the entire day, you are producing a couple orders of magnitude less alcohol than is in 1/10th of a mouthwash treatment (or 1/5th I guess if you use it twice a day).

[space_fountain]

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 the internet usually is, but that also seems to be an easy thing to test for. You can swab someone's mouth who's taken this and see if they still have the mutated bacteria or if it's been out competed

[tadfisher]

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.

[yorwba]

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.