Where does the relentless strength of superbugs come from? – basic research

By Clarice Cudischevitch

Angélica Vieira believes the answer lies in the gut microbiota

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When Angélica Vieira graduated from Belo Horizonte with a degree in biology in 2002, she discovered that the UFMG had research laboratories. She studied at a private university to work during the day and to help at home, since she lost her father very early and decided to knock from door to door: She wanted to do a scientific initiation at the federal university, even without studying there. Prof. Prof. Mauro Teixeira from the Immunopharmacology Laboratory welcomed the future scientist who entered the microbiota universe that was the subject of her Masters and PhD.

“I didn’t look for this area, I entered because it accepted me,” she says. “But it was very lucky because I fell in love with the subject from day one.” Research on gut microbiota has multiplied in recent years – the amount of microorganisms that live in the digestive tract and popularly known as “gut flora” is a misnomer and luckily no longer used. If more is said today about the relationship between him and various health problems, from cancer to depression, it was an unknown world at the time.

In the laboratory where Vieira had taken scientific initiatives, the group was interested in understanding the role of intestinal bacteria in inflammatory processes. It was the only one in Brazil that had gnotobiotic animals, i.e. free from microorganisms: the mice raised there were born by caesarean section (the microbiota only develops after birth), lived in isolation in a bladder and consumed sterile food and water, which prevents microbial contamination.

The group found that these animals did not respond to models of inflammation – in other words, they did not develop disease. It was therefore initially assumed that bacteria are responsible for causing inflammation. However, other studies have shown that in inflammatory bowel diseases such as colitis or chronic, animals without a microbiota had much more severe conditions.

“At that time there were no DNA sequencing techniques, but we have started to explore this area,” says the biologist. The opportunity arose to work with a group from Garvan Medical Research in Australia who identified a receptor in the cells of the immune system that is activated by metabolites produced by the microbiota. The role of these microorganisms in inflammatory processes thus took shape. Vieira dreamed of going abroad but didn’t know how to speak English. He decided to turn around and did a PhD on sandwich.

The work with the Australian group was published in Nature in 2009 when the boom understood the microbiota better. What was observed was that beneficial bacteria predominate in healthy individuals while they are reduced in patients. This indicates that in these cases such metabolites – metabolites – are also reduced and not activated.

These metabolites are created when bacteria consume soluble fiber. Because of this, an unbalanced and low-fiber diet – as is common in the western world and a voracious consumer of ultra-processed foods – can lead to an imbalance in the microbiota known as dysbiosis and promote the development of disease. But the harmful relationship doesn’t stop there.

Angélica Vieira is now exploring a much more destructive potential of this imbalance: the almost relentless development of superbugs protected from all antibiotics. The UN estimates that drug-resistant infections could cause 10 million deaths each year by 2050, and there are those who claim it will be the next pandemic. Incidentally, the scientist believes that Covid-19 will accelerate the multiplication of superbugs as many people have used antibiotics and other drugs in an uncontrolled manner to fight the coronavirus.

The main cause of the emergence and spread of superbugs is precisely the abuse and rampant use of antibiotics, the production of new classes of which has stagnated for twenty years. However, Vieira’s hypothesis is that the microbiota could act as an important reservoir for several resistance genes. Bacteria are organisms with a tremendous ability to transfer genes, including antibiotic resistance genes, to other bacteria.

“The WHO ran a major campaign about fifteen years ago highlighting the dangers of indiscriminate antibiotic use and encouraging more restrictive measures. In recent years, however, resistance has increased enormously. Because? “The biologist’s hypothesis is that changes in microbiota caused by Western diets may have contributed to the selection and spread of antibiotic resistance.

She’s been investigating a particular superbug, Klebsiella pneumoniae, which has already caused an outbreak of pneumonia in Brazil. “Klebsiella spreads resistance genes extremely easily and there is no effective antibiotic against it.” Part of this difficulty in controlling may be due to its natural presence in our microbiota which, if out of balance, can encourage the superbug to multiply.

Vieira, who volunteered as a scientific researcher for two years because no scholarship was available, now coordinates the Microbiota and Immunomodulation Laboratory at the UFMG’s Department of Biochemistry and Immunology. “I never had any doubt that I wanted to become a scientist, even though I grew up in the country and had no idea how that could happen,” says the miner from Gororós, a district of around five hundred inhabitants, who is now the mother of Estela and Rafael .

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Clarice Cudischevitch is a journalist, communications manager at Instituto Serrapilheira and coordinator of the blog Ciência Fundamental.

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