There's a Microscopic Battle Inside Your Cheese

Sam Westreich, PhD

New research sheds light into the constant life-or-death war happening in your dairy products.

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Oh, the battlefield! Oh, the trauma!Photo by Alexander Maasch on Unsplash

Cheese: it’s delicious, it is a vital component in many foods (and many Tiktok-inspired food abominations), and there’s even some argument that it may be addictive (or, at least, it lights up the same areas of the brain that are triggered by addictive substances).

It’s also not sanitary. In fact, most of the food that we eat isn’t sanitary — not really. From vegetables to bread to dairy products, there are thriving communities of bacteria living on all these surfaces, at least up until they’re all unceremoniously extinguished by stomach acid.

Cheese is especially rich in bacteria, because microbes are a necessary part of the cheese making process. Cheesemakers have closely guarded cultures of bacteria, yeast, or fungi that they add to their milk to obtain their specific variety of cheese.

Because of this, cheese is a great material to study if we want to look at how microbial populations adapt — especially to new predators.

And new research shows that cheese products are, at the microscopic level, an always-changing, ever-dangerous battlefield.

The only thing that scares a bacterium is a phage

The life of an individual bacterium is short and scary. There are many predators in the wild that prey on bacteria, scarfing them down by the millions. Worms, amoebas, tiny crustaceans, snails, and other creatures all hunger for the taste of sweet, sweet bacteria.

Fortunately, these predators aren’t usually a problem for bacteria growing on cheese. Most cheese does not contain any snails or crustaceans. But larger predators aren’t the only threat to bacteria.

Just like how large humans can be brought low by tiny bacterial pathogens, bacteria are also vulnerable to disease. For them, it comes in the form of a type of virus that specifically preys on bacteria: a bacteriophage. These viruses often look like a weird, alien version of the 1960s moon lander.

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A bacteriophage rendering, looking creepy and insectile.Source: Wikipedia

Bacteriophages attack bacteria by inserting their viral DNA. That long cylinder lands on the bacterium’s surface and, like the plunger on a syringe, injects the DNA stored in the polyhedral head down into the body of the bacterium.

Once inside, the viral DNA hijacks the bacterium’s own systems so that the bacterium becomes an enslaved factory, churning out more and more bacteriophage copies. Eventually, the poor bacterium splits open, and the thousands of newly synthesized viruses spill out in search of fresh bacteria to land on and suborn.

Bacteria aren’t completely helpless in this fight. They need defenses, after all; it is estimated there are more than 10^(31) bacteriophages on the planet, more than every other organism on Earth, including bacteria, combined.

(That’s 10,000,000,000,000,000,000,000,000,000,000 bacteriophages, or about 10 nonillion. Give or take a few septillion, of course.)

To help fight off this omnipresent threat, bacteria use a number of defenses. Most of these are molecular weapons, proteins built from genes that the bacteria collect and hoard like a hospital stockpiling antibiotics in a pandemic. There are too many different methods to discuss them all here, but one method has gained fame in recent years: the CRISPR-Cas9 system, which we humans have repurposed as a vital component in today’s gene therapies.

(Before we put it to use for our own goals, CRISPR-Cas9 was a type of molecular scissors, able to cut DNA at a very specific spot. Bacteria use this to help fight off bacteriophages by cutting their DNA to bits before it can start synthesizing copies, tearing up the blueprints before they can be put to use.)

Okay, so we’ve got bacteria, and bacteriophage viruses, battling it out.

How does this link back to cheese?

Looking at the cheese battlefield through sequencing

In order to get a better idea of what the bacteria living in/on cheese were doing, researchers sequenced their RNA, discovering which bacterial genes were actively turned on at the time of sample collection. They matched these sequences against bacterial genomes to determine what their functions were, searching for all the active genes related to viral resistance.

And they found a lot of viral resistance genes. Across their whole study, 17,565 innate immune systems and 1,972 CRISPR-Cas systems were identified. But these different defenses didn’t match up to the different species that were present; they were only present in specific strains at any time, and were rapidly gained and lost.

Similarly, CRISPR works by using a short piece of RNA called a spacer to match to DNA where it is going to make a cut. A specific spacer will match up to a specific virus; since different viruses would have different DNA sequences, you’ll need a different spacer to target each one with CRISPR. In the samples from cheese, even though the bacteria are pretty consistently the same group of species, they showed insane levels of CRISPR spacer variation.

What does this tell us? A couple of things:

  • These bacteria aren’t worried about any specific virus coming in and attacking them; if that were the case, they’d keep a consistent set of defenses. Instead, they seem to constantly hot-swap defenses, looking to try and offer broad protection against a wide range of potential attackers.
  • The bacteria are constantly altering their CRISPR defenses, trying to fight off viruses.
  • It may not be enough; some of the viruses in the samples didn’t match to any CRISPR spacers, meaning that these viruses couldn’t be stopped by the bacteria. Evolutionary war, in action!
  • Even in a relatively closed system (not a lot of new viruses/bacteria being introduced into cheese), there’s constant turnover and rapid evolution needed to survive, as both sides frantically adapt to try and outclass the other.

What can we take away from this?

Overall, this probably won’t matter for most of us. Yes, it’s a little disturbing to know that there’s constant fighting going on between viruses and bacteria inside the cheese you’re about to eat, but these viruses and bacteria aren’t going to attack humans. They’re too busy fighting each other.

This does suggest that we can’t look at viral resistance as being a set skill, one that is stable and inherited. Bacteria are rapidly gaining (and losing) various methods for defeating bacteria, shuffling them around constantly in an attempt to keep ahead of their competition. This is Uno, not poker; it’s not gaining the best hand to keep, but trying to constantly have the best hand for the moment, knowing that you won’t be holding onto any card for long.

This may pay off for cheesemakers — and maybe even for all of us. How do you kill bad bacteria without killing the good ones? Instead of using antibiotics, which kill every bacterium indiscriminately, there’s research into using phage therapy — introducing bacteriophage viruses to specifically target the bacteria we want dead.

Phage therapy, in the short term, could help target pathogens that would screw up the cheese-making process, while still leaving the good bugs to make delicious dairy product.

In the longer term? Perhaps phage therapy will help people with imbalances in their gut microbiome, correcting deviations by eliminating the unwanted microbes, while preserving the other species. This could be a smart, targeted way to attack bacteria, instead of carpet-bombing them all to oblivion.

It turns out that there are lots of lessons to gain from cheese, aside from how to make almost any food more delicious.

At the end of the day, it’s still tasty — bacteria, bacteriophage viruses, and all.

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A microbiome scientist working at a tech startup in Silicon Valley, Sam Westreich provides insights into science and technology, exploring the strangest areas of biology, science, and biotechnology.

Mountain View, CA
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