Study creates bacteria that consume carbon dioxide for growth

Agencies
November 30, 2019

Washington D.C., Nov 30: Researchers have developed bacteria called Escherichia coli, which consume carbon-di-oxide for energy instead of organic compounds.

This creation in synthetic biology highlights the incredible plasticity of bacterial metabolism and could provide the framework for future carbon-neutral bioproduction. The work appeared in the journal -- Cell.

"Our main aim was to create a convenient scientific platform that could enhance CO2 fixation, which can help address challenges related to the sustainable production of food and fuels and global warming caused by CO2 emissions," said senior author Ron Milo, at systems biologist at the Weizmann Institute of Science.

"Converting the carbon source of E. coli, the workhorse of biotechnology, from organic carbon into CO2 is a major step towards establishing such a platform," added Milo.

A grand challenge in synthetic biology has been to generate synthetic autotrophy within a model heterotrophic organism.

Despite widespread interest in renewable energy storage and more sustainable food production, past efforts to engineer industrially relevant heterotrophic model organisms to use CO2 as the sole carbon source has failed.

Previous attempts to establish autocatalytic CO2 fixation cycles in model heterotrophs always required the addition of multi-carbon organic compounds to achieve stable growth.

"From a basic scientific perspective, we wanted to see if such a major transformation in the diet of bacteria -- from dependence on sugar to the synthesis of all their biomass from CO2 -- is possible," said first author Shmuel Gleizer (@GleizerShmuel), a Weizmann Institute of Science postdoctoral fellow.

"Beyond testing the feasibility of such a transformation in the lab, we wanted to know how extreme an adaptation is needed in terms of the changes to the bacterial DNA blueprint," added Gleizer.

The researchers used metabolic rewiring and lab evolution to convert E. coli into autotrophs. The engineered strain harvests energy from formate, which can be produced electrochemically from renewable sources.

Because formate is an organic one-carbon compound that does not serve as a carbon source for E. coli growth, it does not support heterotrophic pathways.

They inactivated central enzymes involved in heterotrophic growth, rendering the bacteria more dependent on autotrophic pathways for growth.

They also grew the cells in chemostats with a limited supply of the sugar xylose -- a source of organic carbon -- to inhibit heterotrophic pathways.

The initial supply of xylose for approximately 300 days was necessary to support enough cell proliferation to kick start evolution. The chemostat also contained plenty of formates and a 10% CO2 atmosphere.

By sequencing the genome and plasmids of the evolved autotrophic cells, the researchers discovered that as few as 11 mutations were acquired through the evolutionary process in the chemostat.
One set of mutations affected genes encoding enzymes linked to the carbon fixation cycle.

The authors said that one major study limitation is that the consumption of formate by bacteria releases more CO2 than is consumed through carbon fixation.

In addition, more research is needed before it's possible to discuss the scalability of the approach for industrial use.

In future work, the researchers will aim to supply energy through renewable electricity to address the problem of CO2 release, determine whether ambient atmospheric conditions could support autotrophy, and try to narrow down the most relevant mutations for autotrophic growth.

"This feat is a powerful proof of concept that opens up a new exciting prospect of using engineered bacteria to transform products we regard as waste into fuel, food or other compounds of interest," Milo said.

"It can also serve as a platform to better understand and improve the molecular machines that are the basis of food production for humanity and thus help in the future to increase yields in agriculture," added Milo.

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Agencies
May 26,2020

Tedros Adhanom Ghebreyesus, the World Health Organisation's (WHO) Director-General, said that a clinical trial of hydroxychloroquine (HCQ) on COVID-19 patients has come to "a temporary pause", while the safety data of the the anti-malaria drug was being reviewed.

According to the WHO chief, The Lancet medical journal on May 22 had published an observational study on HCQ and chloroquine and its effects on COVID-19 patients that have been hospitalized, reports Xinhua news agency.

The authors of the study reported that among patients receiving the drug, when used alone or with a macrolide, they estimated a higher mortality rate.

"The Executive Group of the Solidarity Trial, representing 10 of the participating countries, met on Saturday (May 23) and has agreed to review a comprehensive analysis and critical appraisal of all evidence available globally," Tedros said in a virtual press conference on Monday.

The review will consider data collected so far in the Solidarity Trial and in particular robust randomized available data, to adequately evaluate the potential benefits and harms from this drug, he said.

"The Executive Group has implemented a temporary pause of the HCQ arm within the Solidarity Trial while the safety data is reviewed by the Data Safety Monitoring Board. The other arms of the trial are continuing," Tedros added.

WHO initiated the Solidarity Trial, a plan to evaluate the safety and efficacy of four drugs and drug combinations against COVID-19 more than two months ago, which include HCQ.

According to the WHO, over 400 hospitals in 35 countries are actively recruiting patients and nearly 3,500 patients have been enrolled from 17 countries under the Solidarity Trial.

Tedros added that the safety concern over the drug related only to the use of HCQ and chloroquine in COVID-19, and "these drugs are accepted as generally safe for use in patients with autoimmune diseases or malaria".

"WHO will provide further updates as we know more," he added.

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Agencies
June 29,2020

Washington DC, Jun 29: Young children with narrow retinal artery diameters were more likely to develop higher blood pressure, and children with higher blood pressure levels were more likely to develop retinal microvascular impairment during early childhood, according to a new study.

The first study to show this connection in children was published today in Hypertension, an American Heart Association journal.

High blood pressure, the main risk factor for the development of cardiovascular disease (CVD), can manifest as early as childhood, and the prevalence of high blood pressure among children continues to rise. In previous studies, analysis of blood vessels in the retina has shown promise as a predictor of CVD risk among adults. In the study titled, "Retinal Vessel Diameters and Blood Pressure Progression in Children," researchers sought to predict the development of high blood pressure in children over four years based on retinal blood vessel measurements.

"Hypertension continues as the main risk factor for the development of cardiovascular diseases and mortality," says Henner Hanssen, M.D., the study's lead author and a professor in the department of sport, exercise and health at the University of Basel in Switzerland. 

"Primary prevention strategies are needed to focus on screening retinal microvascular health and blood pressure in young children in order to identify those at increased risk of developing hypertension. The earlier we can provide treatment and implement lifestyle changes to reduce hypertension, the greater the benefit for these children."

Researchers screened 262 children ages six to eight from 26 schools in Basel, Switzerland, in 2014, for baseline blood pressure and retinal arterial measurements. Both measures were taken again in 2018. Blood pressure measurements at both baseline and follow-up were performed in a sitting position after a minimum of five minutes of rest and were categorized based on the American Academy of Pediatrics' blood pressure guidelines. These guidelines utilize the same measurements as the American Heart Association/American College of Cardiology 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.

Results from the analysis indicate: children with narrower retinal vessel diameters at baseline developed higher systolic blood pressure at follow-up; retinal vessel diameters could explain 29 -31 per cent of the changes in systolic blood pressure progression between 2014 and 2018; children with higher blood pressure levels at baseline developed significantly narrower arteriolar diameters at follow-up, depending on weight and cardiorespiratory fitness; and initial blood pressure measures explained 66-69 per cent of the change in retinal arteriolar diameter from baseline to follow-up.

"Early childhood assessments of retinal microvascular health and blood pressure monitoring can improve cardiovascular risk classification. Timely primary prevention strategies for children at risk of developing hypertension could potentially counteract its growing burden among both children and adults," said Hanssen.

Researchers noted limitations of their study include that they could not confirm blood pressure measurements over a single 24-hour period, so they would not account for "white coat" hypertension, a condition where patients have high blood pressure readings when measured in a medical setting.

Developmental stage including puberty status of each child was not accounted for in the study, as well as genetic factors or birth weight - variables that could impact blood pressure development and microvascular health.

In addition, reference values for appropriate retinal vessel diameters in children do not currently exist, so future studies are needed to determine age-related normal values during childhood.

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Agencies
January 26,2020

High-protein diets may help people lose weight and build muscle, but there is a downside to it --a greater heart attack risk. Researchers now report that high-protein diets boost artery-clogging plaque.

The research in mice showed that high-protein diets spur unstable plaque -- the kind most prone to rupturing and causing blocked arteries.

More plaque buildup in the arteries, particularly if it's unstable, increases the risk of heart attack.

"There are clear weight-loss benefits to high-protein diets, which has boosted their popularity in recent years," said senior author Babak Razani, associate professor at Washington University School of Medicine in St. Louis, Missouri.

"But animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems. We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health," Razani added.

The researchers studied mice who were fed a high-fat diet to deliberately induce atherosclerosis, or plaque buildup in the arteries.

Some of the mice received a high-fat diet that was also high in protein. And others were fed a high-fat, low-protein diet for comparison.

The mice on the high-fat, high-protein diet developed worse atherosclerosis -- about 30 per cent more plaque in the arteries -- than mice on the high-fat, normal-protein diet, despite the fact that the mice eating more protein did not gain weight, unlike the mice on the high-fat, normal-protein diet.

"A couple of a scoop of protein powder in a milkshake or smoothie adds something like 40 grams of protein -- almost equivalent to the daily recommended intake," Razani said.

"To see if protein has an effect on cardiovascular health, we tripled the amount of protein that the mice receive in the high-fat, high-protein diet -- keeping the fat constant. Protein went from 15 per cent to 46 per cent of calories for these mice".

Plaque contains a mix of fat, cholesterol, calcium deposits and dead cells. Past work by Razani's team and other groups has shown that immune cells called macrophages work to clean up plaque in the arteries.

But the environment inside plaque can overwhelm these cells, and when such cells die, they make the problem worse, contributing to plaque buildup and increasing plaque complexity.

"In mice on the high-protein diet, their plaques were a macrophage graveyard," Razani informed.

To understand how high dietary protein might increase plaque complexity, Razani and his colleagues also studied the path protein takes after it has been digested -- broken down into its original building blocks, called amino acids.

"This study is not the first to show a telltale increase in plaque with high-protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques," said Razani.

"This work not only defines the critical processes underlying the cardiovascular risks of dietary protein but also lays the groundwork for targeting these pathways in treating heart disease," he added.

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