Al hacer clic en "Permitir", acepta el almacenamiento de cookies en su dispositivo para mejorar la navegación del sitio, analizar el uso del sitio y ayudar en nuestros esfuerzos de marketing. Consulte nuestra Política de privacidad para obtener más información.
An alfajor
Edición
Edición Digital
004

The world we don't see

Chloroplast, 2011. This cross section through a chloroplast shows the two-layered membrane at the top and the stacked grana below. doi: 10.2210/rcsb_pdb/goodsell-gallery-010
Writer:
Ester Azzola
In COLLABORATION with:
Images:
Molecular Landscapes by David S. Goodsell, RCSB Protein Data Bank. CC-BY-4.0 licence
Chloroplast, 2011. This cross section through a chloroplast shows the two-layered membrane at the top and the stacked grana below. doi: 10.2210/rcsb_pdb/goodsell-gallery-010
Edición
Edición Digital
004

The world we don't see

Writer:
Ester Azzola
In COLLABORATION with:
Images:
Molecular Landscapes by David S. Goodsell, RCSB Protein Data Bank. CC-BY-4.0 licence
Bacteria have survived every major disaster experienced on Earth yet it is believed that they were only discovered in the 17th century by the Dutch scientist Antoine van Leewenhoek. As Ludger Wess explains in The Curious World of Bacteria, bacteria’s resilience and diversity is astronomical. There are more than 14,000 species of bacteria which are known today and nobody knows the exact number of bacteria species but there could be as many as roughly five times the number of stars in the milky way galaxy. This is a feature that takes us through the multilateral yet unseen world of bacteria, the earliest evidence of life on Earth.
No items found.
  1. Last Universal Common Ancestor, 2018. This speculative painting depicts the primordial cell that gave rise to all life on Earth. There are many theories about when and where LUCA arose, and what it looked like. The proteins included in this illustration are largely based on a recent analysis of modern bacterial genomes, looking for commonalities to give clues about the composition of LUCA. This study sees LUCA as not using oxygen and able to synthesize all of its component biomolecules from raw materials available in the environment. It also sees LUCA living in hydrothermal vents and being dependent on conditions and molecules that are present there. doi: 10.2210/rcsb_pdb/goodsell-gallery-035
  2. Red Blood Cell Cytoskeleton, 2020. A cross section through a red blood cell is shown at the bottom, with hemoglobin in red and the cell membrane in purple. A distinctive cytoskeleton forms a structural network bracing the membrane, with several large membrane-bound protein assemblies and short actin filaments, all linked by long, flexible spectrin proteins. Blood plasma is shown at the top. doi: 10.2210/rcsb_pdb/goodsell-gallery-031
  3. RecA and DNA, 2021. Recent work has shown that RecA protein (in turquoise) associates with DNA and forms a long, thin filament that stretches through a cell, providing a scaffold to assist with the pairing of homologous strands during DNA repair. Here, several sites in the DNA are temporarily pairing with the RecA DNA filament as the filament searches for an exact pairing. doi: 10.2210/rcsb_pdb/goodsell-gallery-038
  4. Blood, 2000. This illustration shows a cross-section through the blood, with blood serum in the upper half and a red blood cell in the lower half. In the serum, look for Y-shaped antibodies, long thin fibrinogen molecules (in light red) and many small albumin proteins. The large UFO-shaped objects are low density lipoprotein and the six-armed protein is complement C1. The red blood cell is filled with hemoglobin, in red. The cell membrane, in purple, is braced on the inner surface by long spectrin chains connected at one end to a small segment of actin filament. doi: 10.2210/rcsb_pdb/goodsell-gallery-003
  5. Myoglobin in a Whale Muscle Cell, 2021. This illustration shows whale muscles, which contain many myoglobin molecules (red) to store oxygen during their deep dives. This cross section shows the space between two muscle sarcomeres, which are shown at right and left with actin thin filaments in yellow and myosin thick filaments in tan. The space also includes many glycolytic enzymes and other enzymes involved in energy production (blue) and glycogen granules (purple). A tubule of the sarcoplasmic reticulum is shown at the bottom, with many calcium pumps (blue molecules in the membrane) and calcium storage proteins (green) that concentrate calcium inside, for use in control of muscle contraction. This painting was created as part of the celebration of the 50th anniversary of the Protein Data Bank. doi: 10.2210/rcsb_pdb/goodsell-gallery-032

The watercolour paintings of David S. Goodsell integrate information from structural biology, microscopy, and biophysics to simulate detailed views of the molecular structure of living cells. Proteins, nucleic acids, and lipid membranes are shown; small molecules, ions, and water are omitted for clarity. The intention is to make these illustrations as accurate as possible, using information from atomic structure analysis, electron microscopy, and biochemical analysis to get the proper number of molecules, in the proper place, and with the proper size and shape.

Bacteria have survived every major disaster experienced on Earth yet it is believed that they were only discovered in the 17th century by the Dutch scientist Antoine van Leewenhoek. As Ludger Wess explains in The Curious World of Bacteria, bacteria’s resilience and diversity is astronomical. There are more than 14,000 species of bacteria which are known today and nobody knows the exact number of bacteria species but there could be as many as roughly five times the number of stars in the milky way galaxy. This is a feature that takes us through the multilateral yet unseen world of bacteria, the earliest evidence of life on Earth.

LUCA, the first fermenter

Once upon a time, in the Hadean Eon —  when the Earth formed about 4.567 billion years ago — there was a microscopic ancestor common to all modern forms of life. A primitive, thermophilic being that could survive and thrive in temperatures exceeding 45ºC, in what we would consider an environment inhospitable to our standards of comfort. An environment of hot, highly salty water, rich in ferrous metal ions and sulphides, near volcanic vents on the ocean floor. It was in this infernal cauldron that conditions likely came together for the beginning of life.

LUCA — or our Last Universal Common Ancestor from 4.35 billion years ago — was most likely the first organism to engage in anaerobic respiration, or  fermentation. Before the atmosphere became enriched with oxygen, allowing aerobic, oxygen-breathing organisms to thrive, the first forms of life on this planet used fermentation to gather the necessary energy from nutrients available in the environment, without the use of oxygen. This included bacteria.

Bacteria are unicellular prokaryotic organisms. The term ‘unicellular’ means they are formed by a single cell, the smallest living unit. ‘Prokaryotic’ means that the genetic material inside is not enclosed by a defined structure like a nucleus, like it is in our cells. This apparent simplicity of the bacterial cell, with its loose DNA and little else in its internal environment, actually ensures incredible speed in reproduction. We benefit from that speed every time we multiply our sourdough starter to make bread, or ferment milk in a thermos overnight and wake up to freshly made yoghurt.

The other aspect of this simplicity, somewhat hidden from view, lies in the ease with which bacteria ‘interact’ with other bacteria, viruses, animal cells, or plant cells.

When we say that bacteria ‘interact’, we shouldn’t think about it the same way that humans interact: loving each other, signing a contract, getting married, working together, fighting. In the bacterial world, simple organisms change rapidly due to their exponential reproduction. Establishing relationships can mean entering the host organism, inhabiting it stably, and transferring genetic material either wholly or partially. The Theory of Symbiogenesis, formulated by the American scientist Lynn Sagan Margulis, which represents an alternative hypothesis to the Darwinian one, explains a little more about this strange behaviour.

Take, for example, the fact that in each of our cells, there are small organelles — the mitochondria — that function as power plants supplying most of the energy needed for cellular activity. These organelles have a structure different from our cells and seem to behave as independent units, and yet perform essential functions. According to Margulis’ theory, the explanation is that these organelles could have been a prokaryotic cell that, at a very distant point in evolution, merged with an ancestor of our cells, a primitive eukaryote. It was a permanent symbiosis between both types of living beings: the engulfed bacterium (experiencing phagocytosis)* provided energy, and the more evolved eukaryotic cell offered a stable refuge with unlimited food in a mutually beneficial pact.

*Phagocytosis is defined as the ingestion by a cell of a substance, for example, a pigment, or a microorganism, a bacterium, causing it to enter its internal cellular environment for destruction or assimilation.

Is it you or your bacteria?

In a world as anthropocentric as ours, the idea that we owe our abilities and skills to bacteria seems like a joke.

As we saw earlier, with symbiogenesis, there is a way to provide the host organism — whether animal or plant — with extra genetic information contained within bacterial DNA with which the organism comes into contact. This expands and enriches its metabolic possibilities in a unique way. For example, the human body doesn’t just contain the expression of its own genes — it also contains the gene expression of all the other microorganisms that inhabit it.

In cows, for instance, bacteria are responsible for the assimilation of cellulose after passing through their four stomachs. In our human intestines, resident bacteria like Lactobacillus (facultative anaerobic bacteria that can grow in environments with or without oxygen) are known for their ability to ferment sugars into lactic acid as the main product. They are also found in fermented foods like yoghurt, sauerkraut, and kefir. These bacteria play a crucial role in the fermentation and preservation of food and are considered probiotics, meaning they can have benefits for intestinal and overall health. These bacteria, along with Bifidobacterium*, are responsible for the production of vitamins B2, B3, B6, B12, and K. In a 2010 study, researchers found genes in the intestinal bacterial flora of the Japanese population dedicated to producing enzymes for digesting algae, a common ingredient in Japanese cuisine. When looking at the bacterial flora of the American population, where algae is not a dietary staple, the same genes and digestion abilities were not found. Through the ingestion of algae with their associated bacteria, the Japanese population had acquired the ability to extract nutrients from that food.

*Genus of facultative anaerobic bacteria, common in the gastrointestinal tract of humans and other animals, they play a crucial role in the development of the immune system and digestive health during the early years of life.

Bacteria educate and modulate our immune systems. Without them, we wouldn’t be able to survive the flu. They are fundamental in processes that regulate our fertility — the perpetuation of the sapiens species on this planet. They regulate homeostasis, the generation and absorption of nutrients, assist in mood regulation and cognitive processes, compete with pathogenic microorganisms for space and resources, and prevent harmful infections. Bacteria and all the microorganisms that inhabit us are co-responsible for our ability to adapt, compete, and survive in the world we live in.

The number of microbial cells — bacteria, viruses, fungi, and other microorganisms — that colonise various parts of the human body, such as our skin, intestines, mouth, among others, forming the microbiota, is impressive. It is estimated that there are approximately 100 trillion microbial cells in the human body. That’s a number far larger than the number of human cells in the body, representing a population in continuous communication with itself and us — in constant, unpredictable, unexplored coevolution.

Fermentum, from the Latin root of the verb fervere: to move, to boil.

Fermentation is a typical chemical and biological process in which bacteria transforms one organic substance into another. It’s been part of human gastronomy since the early civilizations of Mesopotamia, Egypt, and China, where the first remains of fermented foods were found: in the form of beer, wine, mead, and bread. These foods were often considered sacred and religious. Offerings to the gods, the ultimate expressions of civilisation, were fermented.

Our first meal as mammals is wonderfully enriched by bacteria migrating from the maternal intestine to breast milk, through a ‘secret’ route, a path through the circulatory system known as the enteromammary route. For a long time, human milk was considered a sterile fluid free of microorganisms. However, in 2003, a team led by researcher Rocio Martín determined the presence of commensal and probiotic bacteria and today we know that its probiotic, prebiotic, and immunomodulatory properties are responsible for the newborn’s competitiveness and survival. Thank you bacteria, once again.

For thousands of years, one of humans’ greatest challenges was the preservation of food. What was abundant today could turn into a heap of rot and illness tomorrow. Fermentation was an effective way to preserve food for long periods. For one thing, it created an acidic or alcoholic environment that inhibited the growth of harmful bacteria and other microorganisms. Additionally, the strain of bacteria driving the fermentation occupied an environmental niche, making it harder for others to grow — like getting on a crowded bus without any comfortable seats. So did humans learn to ferment? They observed nature around them, watching what happened in animals, plants, in the food they collected, in damp soils. Birds store seeds in a digestive tract called the crop so they can ferment and become more digestible; squirrels bury acorns, taking advantage of bacteria in the soil. Both elephants and insects, even bats, can recognise a feast of ripe fruit fermenting from afar and are willing to move quite a bit not to miss that intoxicating binge (because almost all mammals do enjoy being a little tipsy).

Smell is the sense that guides animals toward desirable fermentations and away from unsafe ones. In humans, taste has a certain dominance in detecting acidity over orthonasal olfaction, which has lost some dominance (see Anchoa Magazine issue 3, feature The pluriverse of taste for a more extensive explanation of the two pathways).

All vertebrate animals have a hepatic system for alcohol metabolism, a product of fermentation. Primates collect fruits and flowers, pile them up, and patiently wait for ripening and fermentation before consuming them, just like when we choose the most fragrant and ripe fruit at the grocery store. Primates, like us, metabolise alcohol through the enzyme alcohol dehydrogenase*, collecting energy (and possibly joy).

*Alcohol dehydrogenase is an enzyme that helps metabolise alcohol in the body. Its main function is to catalyse the oxidation of ethyl alcohol (ethanol) into acetaldehyde. Subsequently, acetaldehyde is metabolised by other enzymes in the liver for the purpose of elimination. Acetaldehyde is a toxic compound that can cause adverse effects in the body, better known as what we could call a ‘hangover.’ The quantity and activity of this enzyme can vary from person to person and may influence the speed at which the body metabolises alcohol

Nature uses fermentation to deconstruct organic matter and regenerate it: it’s the process that converts energy, returning it to the earth and releasing it again into the infinite. Our ancestors observed and through trial and error, gave life to experiences and culture. If the test result was safe to eat and also provided an improved taste and texture, as in the case of fermented foods, a new technique was adopted.

Fermentation can significantly enhance the taste, texture, and palatability of foods. Amino acids, nucleotides, short-chain fatty acids* — all molecules that tickle our retronasal receptor system — are released during the process. Microorganisms involved in fermentation can break down substances in foods, generating richer and more complex flavour nuances. The acids in yoghurt, the umami of cheese, the carbonation in fermented beverages like beer, kefir, and kombucha — bubbles which are very appealing to the nerve endings of our tongues. Preserved foods are richer, easily digestible, and feature more available nutrients for assimilation.

*Short-chain fatty acids have a skeleton of fewer than six carbon atoms. They are a result of bacterial fermentation and their short chain gives these fatty acids the characteristic of being volatile, which we perceive through our sense of smell. Each with its distinctive aroma, we encounter them as characterising molecules in vinegars, wines, cheeses, solvents, sweat, and butter.

Fermented and raw foods contain beneficial microorganisms, such as probiotic bacterial strains, which can colonise our intestines and promote overall health. To this day, we still don’t fully understand how these processes work, but even ancient cultures knew that fermented foods promoted good health: in China, 2,000 years ago, kombucha was attributed with properties that ensured a long life.

The diet, as anthropologist Joseph Henrich would define it, of WEIRD people (raised in a Western society, educated, industrialised, rich, and democratic) is undergoing a significant split. On one hand, we are increasingly moving away from consuming traditional fermented foods, spreading our bodies with hand sanitizer, and eating ultra-processed and long-life packaged foods. Furthermore, the prevalence of antibiotics in food chains and household self care products today is higher than ever before. Packaged, sterile, standardised, high-temperature processed, irradiated, disinfected food. Are we testing the healthy proliferation of the microbiota in our intestines and bodies? What happens if this mechanism of symbiosis, the coexistence which we have with bacteria, disappears or is damaged?

On the other hand, diseases and ailments related to the body’s microbiota are emerging, and we increasingly turn to expensive laboratory-made probiotic and prebiotic supplements. We buy miraculous kefirs in single-use plastic bottles, forgetting that in all food cultures — except fast food — there are fermented foods brought to the table daily, such as pickles, yoghurt, and cheese.

Modern dichotomy worships bacteria encapsulated in pills while simultaneously declaring war on them with lethal mouthwashes, disinfectant detergents for bodies, surfaces, and clothes. It’s a promise of true havoc on the microbial world.

We are experiencing a paradigm shift in consumption (for those who can choose). On the one hand, there is a need for reconnection with the world of nature, championed by the new Nordic gastronomic movement: slow living, autonomous food production, foraging, sourdough bread, ancient grains, fermented pickles, and artisanal garum. On the other hand, there is an obsession with the sanitation of everything around us as if we were entering an operating room.

If I say microbes, do I mean diseases?

It was autumn of 1848 when, after a wave of deaths caused by the second cholera epidemic in England, John Snow, a physician and researcher from York (United Kingdom), decided to apply his research experience and keen insight to find a solution — or at least an explanation — to the macabre affair. The disease was ravaging the city of London, and the aetiology — the cause — and its mode of transmission was not known with certainty.

The interpretative scenario was divided between ‘contagionists’ and ‘miasmatics’. According to the former, cholera was acquired through contact with the sick, advocating drastic sanitary measures such as quarantines, confinement, and burning of clothes. For the latter, it was the winds and toxic vapours, miasmas, emitted by decomposing matter and corpses that were responsible for the spread of the disease.

Snow, with his sharp and observant mind, went beyond the two theories and found a common factor among all the sick, something as simple as it was vital. They drank water from the same pumps, contaminated by something that at the time was neither sought nor could be seen clearly, due to the lack of technology. The microscopic culprit was the cholera bacterium, Vibrio cholerae.

In early September 1854, in an area of London called Golden Square, there was an unusually intense cholera epidemic outbreak where nearly 500 people lost their lives in just a few days. Snow hypothesised that the outbreak was due to the ingestion of contaminated water from the public pump located on Broad Street and alerted the local health authority, which decided to disable the Broad Street pump by removing its handle — a measure that was able to stop the contagion in that area.

It is anecdotal that Lion Brewery — a brewery near the Broad Street pump — recorded very few deaths in a high-mortality area: the brewery workers, fearful of drinking water from the pump after the initial rumours, only drank beer.

Dr. Snow’s work inaugurated a health paradigm called ‘germ theory’, and it boomed in the second half of the 19th century.  The theory sought a single culprit for every disease; a linear and explanatory relationship for everything in medicine. It made progress by crossing culprits in the microbial world off the list: diphtheria, pneumonia, polio, tuberculosis. The development of vaccines, the hope placed in antibiotics. The ‘Henle-Koch postulates’ (1840 and 1978), hygiene rules that begin to be public knowledge, handwashing becomes part of habits in obstetrics, surgery, and homes. From the second half of the 20th century, things changed, and a new way of observing tried to give reason to what happened with those diseases that were not infectious, presenting greater complexity. People began to talk about factors like risk, black box, and multifactoriality. It is still the dominant theory today, although many authors have contributed to considering biomedical phenomena with a biopsychosocial perspective.

Bacteria began to be viewed as symbiotic, as helpers. Today we study the relationships between the microbial world inside us and cancer, depression, eating behaviours, infertility, autism, and metabolic syndrome — just to mention a few of the many fields of microbiology research.

Current trends in microbiological research focus on antibiotic-resistant bacteria, therapies based on bacterial competition, bacteriophages, and microbiome modulation approaches. Genetic engineering and biotechnology tirelessly investigate the production of chemical compounds, bioplastics, enzymes, and other products useful for everyday life and with a lower environmental impact through the genetic manipulation of bacteria. We seek bacterial populations in extreme environments, from desert soils, oceans, mountain peaks, and even on other planets, to understand and try to cope with the impact of climate change.

The food industry has not lagged behind in the use of bacteria. Alongside the more traditional use of fermentations to preserve food, in recent years, it has introduced new proposals that deserve some reflection before purchase. Alongside the growing list of functional foods driven by our anxieties for eternal health and youth, now, in addition to kale, oats, green tea, almonds, chlorophyll shakes and smoothies, we can find granola bars and breakfast cereals enriched with probiotics. There are also foods for babies and children, such as infant formulas, desserts, and compotes supplemented with beneficial bacteria. The trend even extends to pet foods fortified with beneficial bacterial strains.

Food biotechnology employs specific aromatic bacteria, genetically modified or selected to produce specific aromatic compounds, such as certain esters or aldehydes. These compounds can be used to enhance the aroma of food products and beverages with sensorial profiles appealing to consumers. Various types of organic compounds are distinguished based on the functional groups they contain, which are responsible for the chemical behaviour of the molecule. Esters are organic substances found in many natural products, both animal and vegetable in origin. They typically have pleasant odours and are responsible for the aromas of fruits, flowers, and essential oils. Industrially, esters are in demand as food additives to improve the aroma and flavour, such as banana flavour in candy or pineapple flavour in lollipops. For aldehydes, common uses include organ preservation, disinfectants, resins, dyes, and fertilisers. Some aldehydes of plant or synthetic origin are added to certain products to impart odour and flavour. In pastry, benzaldehyde is responsible for the taste of bitter almonds, cinnamaldehyde gives the characteristic smell of cinnamon, and aldehydes are also the molecules that give the scent of vanilla, camphor, and cloves.

Another example, providing an overview of the challenging fields of application for bacteria, is the study of their application in cell culture for meat production. This is used to produce growth factors and hormones necessary for animal cells to grow and multiply.

Throughout this article, we can see that in just 300 years, we have had many emotional responses to these beings that most of us have never seen and will never see with our eyes.

We started with fascination for their discoveries, the result of different intuitions over the centuries. From the earliest observations by Robert Hooke and Marcello Malpighi; followed by Athanasius Kircher in 1659, who with the help of a compound microscope, was the first to observe bacteria in the blood of plague victims. The credit was recognized in 1674 to the Dutch merchant Anton van Leeuwenhoek, who observed microscopic life that he defined as ‘animalcules.’

We went from a united struggle to overcome them to an amazement of knowing that they have always been with us — and that we are the evolutionary result of interaction with them. From collaboration in providing us with delicacies, preparing sacred and basic foods such as bread and wine, ensuring food during months of scarcity, we returned to hating them and confronting them with misguided weapons, generating resistance and lethal superbugs*.

MRSA is a strain of the bacterium Staphylococcus aureus that has become resistant to various antibiotics that form the first line of defence against this bacterial strain, initially to penicillin and later to methicillin. It represents one of the most significant challenges we face in public health, including mortality, complications during hospitalisation, and healthcare costs.

We asked for forgiveness, raising monumental shelves of expensive supplements. We learned to taste them in restaurant menus in gastronomic capitals. Now, we turn to them again, not only to use them to feel better but as the last hope in a world that scares us, and we no longer understand the rules. Perhaps they are winning the war for survival. 🐟

Bibliografía
  1. Haldane, J. B. S. (1929). Origin of Life. The Rationalist Annual, (148), 3-10.
  2. Sagan, L. (1967). On the origin of mitosing cells. J Theor Biol, 7(3), 255-74. doi: 10.1016/0022-5193(67)90079-3. PMID: 11541392.
  3. Hehemann, J. H., Correc, G., Barbeyron, T. et al. (2010). Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature, (464), 908-912. https://doi.org/10.1038/nature08937
  4. Jost, T., Lacroix, C., Braegger, C. P., Rochat, F. y Chassard, C. (2014). Vertical mother-neonate transfer of maternal gut bacteria via breastfeeding. Environ Microbiol, (16), 2881-2904.
  5. Martin, R., Langa, S., Reviriego, C., Jiminez, E., Marin, M. L., Xaus, J. et al. (2003). Human milk is a source of lactic acid bacteria for the infant gut. J Pediatr, (143), 754-758.
  6. Urquía, M. L. (2006). Teorías dominantes y alternativas en Epidemiología. Ediciones de la UNLa (Colección Salud Comunitaria). http://isco.unla.edu.ar/edunla/cuadernos/catalog/view/1/2/5-2
  7. Benjaminson, M. A., Gilchriest, J. A. y Lorenz, M. (2002). In vitro edible muscle protein production system (MPPS): stage 1, fish. Acta Astronaut, 51(12), 879-89. doi: 10.1016/s0094-5765(02)00033-4. PMID: 12416526.