Fact of Fiction - Can Pathogens Survive in Beer? The RDWHAHB Edition

Its time for the third instalment of my pseudo-series Can Pathogens Survive in Beer (Part 1 - of course they can, Part 2 - Moulds). To summarise parts I and II, yes there are a number of pathogens that survive in beer, and yes, moulds can release poisonous mycotoxins into beer, but generally speaking proper sanitation and controlling your brewing environment can eliminate these risks.

Today's edition is a little different; my previous posts get "cited" a lot by people who seem to have been scared by my posts away from testing new organisms as potential brewing bugs. As one example, a few months ago at Milk the Funk a discussion on the potential use of Lachancea fermentati (a lactic-acid producing yeast) to make a "single organism" sour-beer. The interest readily split into two groups after a case report was found of a patient in Texas who suffered fungemia (blood infection) with Lachancea fermentati. This led many people who at first were anxious to try brewing with this yeast to become fearful about even letting it near their brewery. Yet I, and a few others, made beers with this yeast...and we're all still here and no one got sick. So what is going on? Why would I (a microbiologist by trade) risk making a beer with a known pathogen?

The answer, as always, is below the fold...

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What Makes a Pathogen?

Before we delve further into this question, its worth revisiting the topic of what makes a pathogen. The answer is surprisingly unclear - there is no clear-cut or easy way to determine if an organism has pathogenic potential; the reason for this has more to do with the nature of the human body than the microorganisms. Our bodies use a "layered" defence to protect us from microorganisms. The first "layer" is simply barriers - skin, the lining of our lungs and intestines, etc - all are tightly sealed surfaces that act to keep bugs out. But they are also easily penetrated; bona-fide pathogens typically have toxins or other mechanisms that allow them to break down these barriers, but by accident we also "hole" these barriers every day - cuts, abrasions, even the act of digesting foods open up entry points for microorganisms to gain entry into our body.

The second "layer" is temperature and pH - our bodies normal operating temperature of 37C is well above what most microorganisms find comfortable, while the higher temperatures of a fever push our body temperatures above what many microorganisms (even pathogenic ones) can stand. pH also plays a role; especially in our stomach where very acidic conditions (pH as low as 1.5) kill many microorganisms before they enter the less acidic intestinal tract.

The third "layer" is nutritional - key elements required for both our health and the growth of pathogens (e.g. iron and other metal ions) are highly sequestered by our bodies, preventing pathogens from gaining access.

The four "layer" is our immune system - a combination of chemical and cellular processes which have a remarkable ability to target and kill microorganisms.

Normally, pathogens have ways of overcoming these barriers - as one example, Staphylococcus aureus (an organisms which is an occasional topic of research in my lab) is temperature and acid resistant, secretes streptolysins - toxins which can break open barriers as well as kill immune cells - and secretes siderophores which can"pull" the minute amounts of iron our bodies fail to sequester into the pathogen. Through these (and other) mechanisms, Staphylococcus can readily infect humans...and its burgeoning antibiotic resistance has catapulted it to the top of the list of pathogens of concern in the developed world.

Most microorganisms lack the arsenal of Staphylococcus, and therefore are not "classical pathogens"...but as you can imagine a number come close, and therefor may be able to produce an infection if something impairs some one of our defence "layers" that the microorganism is otherwise unable to penetrate.

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Consider Saccharomyces

Every day billions (literally) of meals are consumed containing foods and beverages prepared using Saccharomyces cerevisiae - i.e. brewers/bakers yeast. Certainly this microorganism must be safe! But is it?  Consider our "layers" of defence:

1. Barriers: S. cerevisiae lacks any tools to penetrate our bodies barriers. So were safe...well, except for that irritating detail that dozens of holes get made in our barriers every day through mechanical means; especially in the intestinal tract where we most often encounter S. cerevisiae. Strike 1...
2. pH and temperature: Three words - sour beer & kveik. In other words, we use S. cerevisiae in the brewing community under pH and temperatures equivalent to those of our bodies. Strike 2...
3. Nutritional: While S. cerevisiae does not have the nutrient acquisition capabilities of S. aureus, we often forget that S. cerevisiae's natural habitat is the nutrient-poor environment of tree bark. As as such S. cerevisiae has a pretty astounding set of tools to acquire nutrients from nutrient-poor environments (e.g. iron). This may not be bona-fide pathogen-level nutrient acquisition, it is a capacity well above what most environmental organisms would likely be equipped with. Strike 3...
4. Immunological: Luckily, biology isn't 3-strikes and you're out. While S. cerevisiae has the theoretical capability to act as a pathogen (assuming barrier damage), it has absolutely no defences against our immune system. Simply dumping serum (the liquid portion of your blood) from a healthy person onto S. cerevisiae is enough to impair its growth, and my favourite immune cells (macrophages) literally will eat S. cerevisiae like candy.

So three cheers for our immune system, because it is what allows us to enjoy beer.

Oh wait, S. cerevisiae infections can and do occur - in one one hospital at a reported rate of 6 per month!

So should we all stop brewing? Of course not! It turns out that fungal infections with yeasts such as Saccharomyces, Picha and Lachancea are relatively common, but only in patients who are severely immunosuppressed, or who are co-infected with a more serious pathogen, or who have had a series of particularly unfortunate medical events (e.g. gut-wall damage during a conventional colonoscopy).

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So Relax, Don't Worry and Have a Home Brew...But Brewed With What?

Up to this point I don't think I've done anything to assuage any concerns, but the take-home message is if other things go wrong with your body, the number of organisms that may cause problems is immense (and not limited to those which can be used to make beer). If you are suffering a serious infection, or are immunosuppressed (e.g. undergoing a transplant, cancer treatment, have HIV/AIDS, etc), or have suffered a recent injury to your intestinal tract, you probably should avoid drinking/eating anything prepared with living microorganisms in it - and that includes probiotic pills, yoghurt (yogurt for my American readers), sauerkraut, and so on. And, of course, avoiding any alcohol (even if it is otherwise sterile) is generally a good idea when you're ill or injured.

But if you're healthy and hale there is very little to worry about. And a few simply guidelines can help ensure your safety.

If brewing using wild/coolship-style beers: make sure that you are taking the proper precautions - pre-acidify your wort and maintain proper sanitation (wild brewing is not an excuse for poor sanitation). Once your beer is brewed, do not start sampling until they smell fine, have reached a pH below 4.0, and reached a minimum alcohol content of 2.5%. Anything that smells bad, has mould, or any oddly coloured organisms in it needs to be dumped - as does any beer which does not reach an appropriate pH and alcohol level (again, below 4.0 and above 2.5%, respectively) after a month or so. These simple rules have kept brewers safe and healthy for decades centuries millennia.

If you're purifying bugs to test as pure cultures: make sure you know what you're doing. Your best sources for bugs are always going to be beers that are already proven safe - i.e. a wild brew that has met the conditions mentioned above. Other safe sources are bottle dregs from other wild/sour beers, other fermented foods and human-grade probiotic preparations (pills/drinks/etc). If getting purified organisms from non-food sources (yeast/bacterial banks/suppliers, research scientists, etc), be sure to do your homework. Stay away from bona-fide pathogens such as Candidia albicans, anything from the Cryptococcus and  Malassezia genera, and the nastier strains of Rhodotorula (R. mucilaginosa, R. glutinis, and R. minuta). Avoid anything reported to produce mycotoxins. And as always, if in doubt don't use it.