The intestinal flora can extend life

  A study carried out by an international team led by researchers from Salamanca has shown that the microbiota or intestinal flora can significantly affect the life span of their hosts. Using the worm 'C. elegans', which is commonly used as a model in biomedical studies, researchers have determined that this nematode lives 50 percent less when its intestinal flora produces antioxidants. The work has just been published in the prestigious magazine specialized in aging 'Aging'.

It has been known for years that the gut microbiota plays an extremely important role in human health. Numerous studies have focused on analyzing the composition of the bacterial community and other microorganisms in the human intestinal tract. In this sense, various studies have related alterations in the communities of typical intestinal bacteria with sensitivity to immune problems, obesity or cancer, among others.

“In our work we have used the nematode worm 'C. elegans 'to investigate the effect that the intestinal microbiota exerts on the aging process ”, explains Adolfo Sánchez-Blanco, first author of the work, who details that' C. elegans' lives naturally in the soil, where it feeds on bacteria that colonize its gut and establish microbial communities.

'C. elegans' is an animal just one millimeter in length that is widely used in biomedical studies. In fact, in just over a decade, three Nobel Prizes have been awarded to researchers who made their discoveries in this organism.

A fundamental limitation when studying the importance of the intestinal microbiota in different aspects of health is the complexity derived from the thousands of species of bacteria and microorganisms that live in our body. To simplify this problem, the researchers used the worm 'C. elegans 'and studied the extent to which two different bacteria,' E. coli 'and' B. subtilis ', can influence the aging of' C. elegans'.

According to their results, the worms kept with 'B. subtilis 'live 50 percent longer than worms kept with' E. coli '. When analyzing the cause of this difference in longevity, they observed that the cellular content of the worms kept with 'E. coli 'is abnormally less oxidized than the cellular contents of worms kept with' B. subtilis'. Specifically, they found that 'E. coli 'naturally produces the powerful antioxidant coenzyme Q, while' B. subtilis' does not produce this antioxidant.

"Our results indicate that the intestinal microbiota can affect the aging process of the host animal and detail that, in the case studied, the nematode 'C. elegans 'lives considerably less in the presence of a flora composed of' E. coli 'than of a flora composed of' B. subtilis 'due to the excessive antioxidant effect that coenzyme Q produced by' E. coli 'generates ”, emphasizes Sánchez-Blanco.

Likewise, the work suggests that the excessive use of antioxidants could cause a shortening of life, that is, "an effect exactly opposite to what is commonly thought." "In fact, coenzyme Q is a dietary supplement commonly used for its antioxidant effects," he adds.

An international and interdisciplinary team

Adolfo Sánchez-Blanco, the main author of the work, is from Salamanca and currently works as a professor of Biology at the University of Hartford (Connecticut, USA). This work was carried out mainly in the Cancer Research Center (CIC) of Salamanca where Adolfo Sánchez-Blanco was working from 2011 to 2014 with a JAE-Doc contract from the CSIC, in the group of Dr. Faustino Mollinedo, who is also one of the authors of the work.

Also participating in the study were Alberto Rodríguez-Matellán (currently at the Severo Ochoa Molecular Biology Center), Ana González-Paramás and Susana González-Manzano (both belonging to the Nutrition and Bromatology Unit of the Faculty of Pharmacy of the University of Salamanca ), as well as Stuart K. Kim, professor of genetics at Stanford University (USA).

Sánchez-Blanco studied Biology at the University of Salamanca but carried out her research career in the US where she completed both her doctorate (at the University of Connecticut) and her post-doctorate (at Stanford University). In 2011, and after 14 years researching in the US, he moved to Salamanca with a CSIC contract but in 2014 he had to return to the US after finishing his research contract and due to the lack of prospects to finance his work

When the most basic research comes to the aid of the most applied: the origin of CRISPR-Cas

  Francis Mojica, a microbiologist at the University of Alicante, and Lluis Montoliu, a CIBERER researcher at the CNB-CSIC, have published a joint review article on the CRISPR-Cas technique in the journal Trends in Microbiology , of the Cell Press group, one of the the most important scientific publications internationally. In science, on many occasions, great revolutions have their origin in the smallest beings. This is the case of CRISPR-Cas, the most revolutionary gene editing technique of the last decades. A secret jealously guarded by bacteria for millions of years until a microbiologist, Francis Mojica, from Alicante, discovered it.

This review article describes the history of this technique from the point of view of a microbiologist and geneticist. "For the first time - indicate the authors -, we have joined two experts in very disparate areas (a basic researcher who works with microorganisms and an expert in mammalian genetics) to give this novel technique the dimension it deserves"

The article highlights the basic science and work of all the microbiologists who have investigated the defense system of bacteria for more than two decades so that, in the last three years, geneticists have been able to take advantage of the system for gene editing.

“The CRISPR-Cas system has evolved in bacteria over millions of years. What we use today for the benefit of mammals derives from millennia of evolutionary optimization in bacteria ”, explains Francis Mojica, who was the discoverer of CRISPR in archaea and father of the name of the technique.

For his part, Lluis Montoliu is a pioneer and reference in Spain in the application of the genetic cutter technique and recalls the great technical difficulties that the modification of the mammalian genome entailed for decades. "The ease and efficiency that the CRISPR-Cas system offers us is really surprising and very exciting," says the scientist. But it is important not to forget the origin of this technique: it was microorganisms and nature that, once again, made an innovative solution available to us ”.

In the review, the two researchers collect the history of CRISPR-Cas over the past 20 years. From the first signs of its existence in the late 80s, through the studies that identified it as an immune defense system of bacteria against viruses and other infectious elements.

In 2012, for the first time, it was proposed that the CRISPR-Cas system could be used as a highly efficient gene editing tool in any organism. “That's when things got rushed: it caught the attention of genetic engineering experts and in the next three years the technique rose to prominence. In 2015, it became the discovery of the year according to Science and was on the front page of newspapers around the world, ”the authors say.

In the last three years, CRISPR-Cas tools have revolutionized biology and biomedicine. The technique makes it possible to generate very specific mutations in the genome of any living being. One of the most relevant applications consists in the generation of animal and cellular models for the study of human diseases. According to Montoliu, who focuses his research on the study of rare diseases such as albinism, "it is now easier to reproduce pathologies such as albinism in animals in order to study their etiology, search for new early diagnosis methods and possible treatments."

The authors admit that there is still work to be done for both microbiologists and geneticists, “perhaps there are still other similar systems in prokaryotes to be discovered that facilitate the genetic modification of eukaryotic organisms. It may have already been described, but we do not yet know its usefulness. Meanwhile, we have to continue working to improve this new tool so that it can be applied in therapy against human genetic diseases ”.

A new microscopy technique takes images with atomic resolution of the structure of salts dissolved in water

 A team of researchers from the Higher Council for Scientific Research (CSIC) has developed a new technique of microscopy of forces in three dimensions that allows taking images with atomic resolution of the organization and structure of salts dissolved in water. The results of the study, published in the journal Nature Communications, could be applied in various scientific fields such as materials science, energy, and molecular biology.

“This technique breaks an existing paradigm in force microscopy that establishes that atomic resolution is only obtained on flat surfaces, that is, in two dimensions. The new technique displays atomic resolution images in a three-dimensional volume. This technique has allowed us to observe that in the proximity of a solid surface, common salt is organized with a structure that simultaneously presents the properties of a solid and a liquid. It is the first time that this type of behavior has been observed ”, explains the CSIC researcher Ricardo García, from the Madrid Institute of Materials Science.

The developed method provides images of how the atoms of electrolyte salts dissolved in water such as common salt (sodium chloride) or potassium chloride are arranged in the vicinity of a surface. The images show that in the vicinity of a solid surface and below the saturation concentration, the sodium and chlorine atoms organize themselves with a different structure than their crystalline structure.

“We have been able to observe that common salt is organized with a structure that simultaneously presents properties of a solid and a liquid (the high mobility of ions and water molecules). This technique may have applications in the development of new methods to accumulate energy and in nanomedicine to understand the interaction between drugs and proteins at the molecular level.

The research is funded by the European Science Foundation, 3DNanoMech project, aimed at designing and constructing a high-speed force microscopy method to characterize solid-liquid interfaces with atomic and molecular resolution.

The deficiency of some bacteria can cause health problems for babies even before they are born

  The microbiota, made up of billions of microorganisms such as bacteria, viruses, and fungi, can have important implications for health and can influence the response that our body has to treatments against AIDS or cancer. That is why the first years of a person's life are an opportunity to introduce changes and prevent these problems.

In the case of babies, the deficiency of some bacteria can increase the risk of developing asthma. This is demonstrated by a recent study led by Stuart Turvey, professor of pediatrics at the University of British Columbia (Canada).

After monitoring 5,000 children, the study proves that babies with alterations in four types of intestinal bacteria during the first 100 days of life have a higher risk of suffering from asthma, a disease that affects 300 million people worldwide. "In the lab, managing these four missing bacteria appears to reduce the risk of asthma, but we don't know for sure," says Turvey.

This is one of the novelties on the microbiome that have been made known at an international meeting called by B · Debate, an initiative of Biocat and Obra Social "la Caixa" in conjunction with the IrsiCaixa AIDS Research Institute, which took place at CosmoCaixa on June 30 and July 1.

The constitution of the childhood microbiome is of great relevance for the health of the person until adulthood. The investigations still have a long way to go, but some progress has been revealed during the debate. Kjersti Aagaard, associate professor at Baylor College of Medicine, is the first researcher to have identified a community of bacteria in the placenta. "Contrary to what was thought, the placenta is not sterile and seems to influence the microbiome of the child more than the way it is born," explains Aagaard.

Until now it was believed that the baby began to acquire the mother's microbiota at the time of delivery, but Aagaard has highlighted that the mother's diet during pregnancy can alter the child's microbiome and its tendency to anxiety.

This new research can help to design new early detection tests (for example, in the case of asthma) or new probiotic treatments. While the investigation is progressing, the experts are clear that "the administration of antibiotics must be controlled, because they are a risk factor," says Turvey in relation to asthma.

During the debate, other issues related to the microbiota, such as HIV infection or cancer, have been put on the table. Roger Paredes, one of the scientific leaders of the debate and researcher at IrsiCaixa, has explained that HIV patients have a less rich microbiota. "Restoring it could improve the evolution of the disease," he says. In the case of cancer, Laurence Zitvogel, from the Gustave Roussy Institute, has spoken of the so-called oncomicrobiòtics: microbes that can influence the effect of chemotherapy against cancer.

They discover how a protein of the immune system kills bacteria and fungi

 Lactoferrin is an innate immune system protein present in mucous fluids such as saliva and milk and which has recognized antimicrobial capacity since its discovery more than 30 years ago. The mode of action by which this protein causes the death of microorganisms has not, however, been disclosed until now. Researchers from the Department of Functional Biology of the University of Oviedo have discovered the mechanism of antimicrobial action of lactoferrin, in simple terms, they have described how this substance eliminates bacteria and fungi.

Scientists from the Asturian academic institution have shown that this protein specifically inhibits an enzyme essential for the survival of these microorganisms - bacteria and fungi - called H + -ATPase. By blocking their activity, microorganisms cannot generate energy (ATP) nor can they control their internal pH. Both the generation of ATP - energy to grow and multiply - and the control of intracellular pH are essential to maintain cell viability. If the H + -ATPase protein does not work, the cell depletes its energy reserves and dies. In addition, by not being able to control the pH, the interior of the cell becomes acidic and other enzymes also stop working.

The finding of the mechanism of antimicrobial action of lactoferrin has just been published in the international journal Antimicrobial Agents and Chemotherapy of the American Society for Microbiology. Professor José Fernando Fierro, principal investigator and professor at the Department of Functional Biology, explains that, despite being an eminently basic research, at least two applications can be extracted from the work.

On the one hand, a new pasteurization method emerges, not described so far, already protected by a Spanish patent, which aims to take advantage of the natural presence of lactoferrin in milk to achieve cold pasteurization , which, according to José Fernando Fierro , it will avoid the loss of some nutritional and organoleptic properties produced by hot pasteurization.

On the other hand, research has identified a therapeutic target on which new antimicrobial drugs can act. The professor at the University of Oviedo explains that the progressive resistance to antibiotics has promoted an intense search for new bacterial targets and for new alternative drugs to existing ones. "The search for bacterial and fungal H + -ATPase inhibitors is one of the most current lines of research. An example of this is the discovery of diarylquinolines, which are already being used to treat tuberculosis resistant to the usual drugs," he says. .

The work of Asturian researchers provides, in addition to these potential applications, a new model for the study of programmed cell death, scientifically known as apoptosis. María Teresa Andrés, co-director of the study, indicates that yeasts are used in laboratories as apoptosis models. For this and until now, scientists have to induce uncontrolled (or uncontrolled) programmed cell death (or cell apoptosis). Lactoferrin induces this apoptosis by interacting exogenously and specifically with H +-Yeast ATPase, which facilitates the study of the chain of intracellular events that lead to cell death. Knowledge of the cellular physiology of apoptosis would allow its manipulation, by inducing or stopping apoptosis in tissues, with a therapeutic purpose.

The studies developed by the University of Oviedo will continue in collaboration with a group from Harvard Medical School (Boston, USA), which has accepted Dr. Maikel Acosta as a postdoctoral researcher, who is waiting to obtain a research grant to join to that group.

Biotechnology to improve vetch and wheat production

 The Department of Microbiology and Genetics of the University of Salamanca is working on a project that aims to improve the productivity of vetch ( Vicia sativa ), a crop that is used as fodder for cattle and is planted in rotation with cereals. To achieve this, the researchers are betting on the design of new biofertilizers based on bacteria that favor the growth of this legume and that, once present in the soil, would also benefit a subsequent planting of wheat.

"The idea is to look for autochthonous inoculants that can adapt to the vetch," says Raúl Rivas González, head of this initiative, which was one of those selected in the call for research projects of the Salamanca Provincial Council, the result of an agreement with the Salamanca academic institution to promote technology transfer in the primary sector.

There are microorganisms that grow in symbiosis with plants, benefiting both species. In this case, in collaboration with farmers from Aldeatejada, scientists have analyzed in recent months the bacteria that could be related to vetch. Although the work is not finished yet, they have selected three. "In particular, two of them are the ones that are more likely to be used as inoculants," says the researcher.

Precisely, the most interesting thing about these new biofertilizers is that they help to obtain good agricultural yields without the need for farmers to resort to other conventional fertilizer products that can be more polluting for the environment. These are microorganisms that do not present any type of problem for the environment or for animal and plant health, so "now we just have to make sure that they have optimal performance in the field."

In fact, European policies are committed to agriculture that is sustainable or beneficial to the environment, called 'greening', and links part of the CAP aid to it. Within this philosophy it is important to renew the nutrients in the soil and applying a fertilizer based on autochthonous bacteria contributes to this.

In this sense, an outstanding aspect of the project is that it not only favors the development of vetch. "Although bacteria do not establish symbiosis with wheat, we can say that they enter a little in its roots and also help its growth," says Rivas González.

The project began last summer and has a duration of one year, a very tight time in agricultural research but that may be enough to be able to present results next September in the framework of the important Salamaq agricultural fair, in which the University de Salamanca has been present in recent years through the Vice-Rector's Office for Research and Transfer to try to establish synergies between science and the primary sector, an essential economic engine for the province.

Identified a new receptor of the immune system against invasive pneumococcal infection

A study led by Dr. José Yuste, a group 2 researcher at CIBERES and the National Center for Microbiology of the Carlos III Health Institute, has made it possible to identify a new receptor present in neutrophils that protects against pneumococcal infection. In this work, recently published in the journal PLoS Pathogens , other researchers from CIBERES Group 2 led by Dr. Ernesto García at the CIB-CSIC, the Hospital de la Princesa and the University College in London have collaborated.

Invasive pneumococcal disease is associated with high rates of morbidity and mortality throughout the world, mainly affecting the pediatric population, over 65 years of age, and immunosuppressed patients. In this study, it is demonstrated that the P-selectin glycoprotein ligand 1 (PSGL-1) present in neutrophils acts as a true phagocytic receptor, recognizing the capsule and the LytA protein of Streptococcus pneumoniae as bacterial ligands. As a consequence, the bacterium is efficiently destroyed by these phagocytic cells, favoring the resolution of the infectious process.

This work is complemented with animal studies using mice deficient in this receptor, demonstrating that the absence of PSGL-1 increases the susceptibility to infection and the severity of invasive pneumococcal disease. The study also shows that during pneumococcal pneumonia, one of the main functions of this receptor is to prevent the spread of bacteria from the lungs to the bloodstream. Once the bacteria have accessed the circulatory system, this receptor would be in charge of effectively recognizing and destroying pneumococci, increasing the survival of the host against this devastating infectious disease.

This study represents a new advance in the knowledge of new defense mechanisms against pneumococcal infections.