Certain odd things interest me – and often they are things which most people would never think of, and even if they did, they would still find it boring or tedious. But it doesn’t bother me at all, and hopefully you will soon get to see why some things are a whole lot more interesting than you thought possible.

As a lover of cheeses, it is quite relaxing for me to research how cheeses are created – and in particular, the complex mix of bacterial and fungal cultures needed to create the idiosyncratic characteristics and flavours of various cheeses.

One of my favourite cheeses, St Nectaire Fermier, is produced by an astonishingly complex and active bacterial community made up of debaryomyces hansenii, geotrichum candidum, brevibacterium linens, torulopsis sphaerica, kluyveromyces lactis, candida sake, cladosporium, aspergillus, etc. Some of these same bacteria are also active in the production of blue cheeses as well, with the characteristic blue furrows developed by either penicillium roqueforti or penicillium glaucum.

What was immediately curious is how these various microbial cultures manage to co-exist so peacefully in the cheeses. It would be more plausible to assume that one of the more aggressive organisms would attempt to wipe out the other species and dominate the whole curdy landscape – and very likely introducing a single sour taste to all cheeses.

But it seems that these various bacterial and fungal colonies are perfectly happy to co-exist in cheeses – acting rather like a perfect multi-racial human society where each race contributes subtly yet significantly to the cultural flavour and well-being of the country.

Obviously, this utopian situation very rarely happens, even with seemingly intelligent human beings, so how come simple bacteria and fungi are so much better at co-existence?

The answer is rather fascinating and also explains why our bodies tolerate the many billions of bacteria in the microbial flora in our intestines.

Some bacteria behaviour: The bacteria in the culture on the left are sensitive to the antibiotics contained in the white paper discs. The bacteria on the right are resistant to most of the antibiotics. (The bacteria are Escherichia coli.) Photo: Wikimedia Commons/Dr Graham Beards

Some bacteria behaviour: The bacteria in the culture on the left are sensitive to the antibiotics contained in the white paper discs. The bacteria on the right are resistant to most of the antibiotics. (The bacteria are Escherichia coli.) Photo: Wikimedia Commons/Dr Graham Beards

Some evidence of bacterial co-operation was already observed in the mid-1960s, notably by a Hungarian-born scientist called Alexander Tomasz. By 1994, scientists had determined that bacteria can indeed detect variations in their environment caused by other bacteria – what’s more, the bacterium can understand the implications of such changes and apply specific survival strategies based on the environmental alterations.

Quorum Sensing

A key piece of research penned in 1994 by the American scientists, Fuqua, Winans and Greenberg, sketched out the concept of Quorum Sensing (QS) by bacteria. The original research was based on marine luminescent bacteria but the principles of QS (or inter-bacterial communication) has since been validated and found to apply to many other mixed colonies of bacterium, including those in cheeses.

At the simplest level, QS is managed by the production and interplay of groups of signalling molecules known as autoinducers – the individual molecules are known as inducers and they are detected by special receptors in the bacterial cells.

A single cell can emit one or more different kinds of inducers. The interaction between inducers and receptors can be quite simple or very complex, depending on various factors, not least being the proximity of other colonies of different bacterium in the same environment.

There are three general types of inducers – the ones produced by Gram-positive bacteria are based on peptides (or chains of amino acids) while Gram-negative bacteria use derivatives of fatty acids.

If you’re curious, Gram-positive bacteria have thicker cell walls which can retain the purple dye used in the Gram stain test (hence the stain effect is positive) – so by inference, Gram-negative bacteria are not stained by the Gram stain test and that’s because their thinner cell walls cannot hold the stain.

Gram positive spherical-shaped bacteria.

Gram positive spherical-shaped bacteria. Photo: Filepic

The final type of inducers is rather rarer and can be produced and utilised by both Gram-positive and Gram-negative bacteria – these inducers are unusual because they are based on boron, an element seldom associated with biomolecules.

Regardless of the types of inducers, the effect at the cell level is like a non-linear equation; that is, the effect can become suddenly chaotic.

However, it is important to note that autoinducers work not only on external bacterium but also within the same colony of bacteria. Within the same colony, the bacteria may choose to wait and expand until the colony reaches a certain size before breaking out of their enclave – this is how many bacterial infections begin.

The bacteria are always aware of its colony size by the amount of autoinducers around it and won’t break out until it is confident of overwhelming the host’s body defences.

The interaction between different species of bacteria goes along somewhat similar lines. Let’s review a situation where the numbers of autoinducers from an external bacterium are slowly growing in an environment colonised by another single host species of bacteria.

While the numbers of external autoinducers are small, nothing much really happens – the inducer molecules are detected, counted by the host receptors and things continue quietly between both colonies of bacteria. And it stays that way until the quantity of inducers detected reaches a threshold (also known as the quorum).

Once the quorum is reached, the host bacteria react rather more frenetically and in several ways – one way is by activating a gene which produces more receptors.

Another way is to activate a separate gene which promotes the production of its own autoinducers – almost like a signal to alert its presence to other bacterium.

There are then several options available to the host bacteria – they can attempt to destroy the external invading bacteria, they can choose to tolerate each other as peacefully as possible, or they can form a partnership with the external bacterium.

Gut flora

Within our own bodies, there are examples of all three kinds of behaviour. Foreign virulent bacteria (also known as pathogens), once detected in the blood or organs, are set upon by the white blood cells in a violent attempt to kill the invaders.

However, in the gut, the externally-introduced microflora work together magnificently with the body – in fact, much of the body’s immune system emanates from, or is enhanced significantly, by the bacterial colonies there.

Probiotics, the natural friendly bacteria are an integral part of the digestive system.

Probiotics, the natural friendly bacteria are an integral part of the digestive system. Photo: Filepic

And within the gut bacteria, there are also countless species which don’t do much for the body but are tolerated either because they are food for the good bacteria or they just don’t have much impact on anything and it is too difficult to rid them from amongst the rest of the gut microflora.

So although there are many kinds of autoinducers swirling around in the gut, it does seem that the various species of gut bacteria generally tend to get along fine with each other.

Back to the cheese

So from the above, you can probably surmise, quite correctly, that the multiple colonies of bacteria and fungi in cheeses also tolerate each other pretty well. The main difference is that they don’t have any noble aims to benefit a higher organism (as with human gut microflora) – most of the bacteria in cheeses just co-exist together in blocks of curdled milk, producing their individual microbial end products, and the final results are the idiosyncratic flavours and textures of cheeses.

As an aside, if you have been drinking alcohol, the ethanol can significantly impact the microflora in the gut, mainly by killing them. Hence it is always a good idea to ingest some probiotic products the next day to replace the lost bacterium. The alternative, of course, is to avoid drinking alcohol but that would be as ridiculous as the idea of me converting to a religion.

Probiotics need prebiotics

It should be noted that it is also quite pointless to ingest probiotics if you don’t provide them with the food they need to survive. Therefore it is a good idea to snack on some prebiotic foods before having the probiotics – the bacteria in the probiotics need the complex carbohydrates (eg. oligosaccharides and inulin) in prebiotic foods to feed on.

So even if you don’t drink alcohol, the microflora in the gut can still die off over time if they are not supplied with prebiotic carbohydrates. Some useful prebiotics are found in tasty ingredients such as mushrooms, leeks, green bananas, okra, onions, garlic, beans, etc.

However, the story actually doesn’t end so simply. What’s quite curious is that certain bacteria appear to understand the principles of QS and hence are able to work around QS – a classic example is a potentially dangerous bacterial species known as staphylococcus aureus. These bacteria appear to know how to avoid producing autoinducers that can be detected by other organisms until it is too late – one reason might be because the genus staphylococcus is often tolerated as part of the normal bacterial flora on human skin and does not get dangerous until it enters the body.

Bacterial behaviour is like… corrupt politicians

It is somewhat like the blatant abuse of trust in political corruption – a corrupt politician, after winning the trust of the people, probably starts on the road to corruption with tiny, imperceptible frauds before expanding to working with other dishonest people and companies to steal vast amounts of money from the public they are supposed to serve. Therefore, there are significant similarities in the behaviours of certain human criminals and pathogenic bacteria.

As an aside, in the case of staphylococcus aureus, there is a deadly strain called methicillin-resistant staphylococcus aureus (MRSA) which is extremely resistant to antibiotics – once contracted, the prognosis for the patient is usually rather poor and the irony is that this strain is quite prevalent in the areas where antibiotics are commonly used, such as hospitals. This is the strain that eventually killed my father.

Hospital-associated Methicillin resistant Staphylococcus aureus (MRSA) bacteria. Photo: Filepic

Hospital-associated Methicillin resistant Staphylococcus aureus (MRSA) bacteria. Photo: Filepic

Bacteria cities and towns

Hiding isn’t the only strategy for invasive bacteria – there are other strategies and a study of these techniques may lead to new innovative treatments to combat infections. It may have other important applications, such as the delay or prevention of food decay – or even improve dental hygiene.

Like humans, many bacteria appear to appreciate that the overall chances for survival can be significantly higher if they organised themselves as communities. Freely floating bacterial cells are known as planktonic cells – and can be individually targeted by the body’s defence systems.

However, as communities, the various species of bacteria can share and benefit from the attributes of each of the species in the community while working under a common protective shield.

A community of such groups of different bacteria is known as a biofilm – and a classic easily visible example is the plaque on teeth.

A biofilm can be considered like a small town or city full of pathogens interacting and communicating with each other via autoinducers. As such, it has been suggested that the autoinducers do more than just signalling a presence – they also appear to be the communication medium for organising the communal work needed for the survival of the biofilm.

The alternative theory is that bacteria sensing the denser presence of another more virulent pathogen would tend to join and support the stronger colony rather than risk annihilation.

More and more other bacterial species would also join the more powerful pathogens, thereby creating a multi-species colony – and eventually the presence of the other bacterium controls the growth and behavioural characteristics of each individual species.

Curiously, this behaviour is also predicted in Hamilton’s Rule for sociobiological altruism which is paraphrased a little as follows: rb > c, where c is the cost of being cooperative, b is the fitness or survival benefit conferred to the bacteria and r is the relatedness or compatibility of the cooperating bacteria to the overall colony.

So it seems that bacteria can also solve some basic mathematical equations. Whatever is next?


Next: Social housing for bacteria