Month: January 2021

Antifungal Compound Discovered in Ant Farms

Researchers in Brazil have discovered an antifungal compound by bacteria living in ant farms, which may have medical applications.

In the fungal farms where attine ants tend as their food source, Pseudonocardia and Streptomyces bacteria produce metabolites which shield the crop against pathogens. Curiously, these metabolites vary across geographic locations.

Attine ants are a type of ant which grow and harvest fungus for food, and are only found in the Western Hemisphere. They first evolved from a common Amazonian ancestor some 50 million years ago, giving rise to some 200 species of ants spread across South and Central America, which share common farming practices. The bacteria at these farms have a symbiotic relationship where they defend against fungi such as Escovopsis in exchange for food.

These metabolites vary considerably, suggesting a fragmented history. Searching a number of ant nests spread across a large geographical area, the researchers discovered that two thirds of the Pseudonocardia strains were producing the same metabolite. They named this newly discovered metabolite attinimicin.The study was the first one where a common, specialised metabolite produced by ant-associated bacteria was found across geographic locations.

Attinimicin inhibited fungal parasites while not harming the fungal crop, but only in the presence of iron. It proved as effective in treating Candida albicans infections in mice as a clinically used azole-containing antifungal. This means that the metabolite could have clinical applications. Attinimicin was shown to have a similar structure to two other metabolites produced by Streptomyces, suggesting the responsible genes have a common evolutionary origin.

Source: News-Medical.Net

Journal information: Fukuda, T.T.H., et al. (2021) Specialized Metabolites Reveal Evolutionary History and Geographic Dispersion of a Multilateral Symbiosis. ACS Central Science. doi.org/10.1021/acscentsci.0c00978.

Prevalence of Antibiotic Resistance is Underestimated

Antibiotic resistance to pathogenic bacteria in humans has spread farther than expected, as it has been discovered that bacteria can swap DNA far more readily than thought possible.

A growing threat, antibiotic resistance has emerged faster than thought possible. Some 33 000 deaths have occurred to antibiotic resistant infections in Europe alone, and finding new antibiotics or even alternatives are a top research priority. Totally different strains of bacteria can swap genetic information through the use of containers called plasmids. Plasmids are small containers of DNA which are kept outside of their chromosomes. When two bacteria come into contact, they can copy plasmids to one another in a process called conjugation (also known as “bacterial sex“). This is the most important means by which bacteria spread antibiotic resistance.

“In recent years, we’ve seen that resistance genes spread to human pathogens to a much greater degree than anyone expected,” said Jan Zrimec, a researcher in systems and synthetic biology at the Chalmers University of Technology. “Many of the genes appear to have originated in a wide array of bacterial species and environments, such as soil, water, and plant bacteria.

“This has been difficult to explain because although conjugation is very common, we’ve thought that there was a distinct limitation for which bacterial species can transfer plasmids to each other. Plasmids belong to different mobility groups or MOB groups, so they can’t transfer between just any bacterial species.”

Among his developments, he has written an algorithm that can sift through substantial amounts of plasmid DNA to pick out sections of DNA which are necessary for conjugation (known as oriT regions, where the enzyme relaxase can bind to and snip out DNA). This algorithm can then sort the plasmids into groups based on their oriT regions. His new method differs from the standard one because it analyses oriT regions by their physiochemical properties instead of searching DNA for the enzyme sequence for relaxase, or the point where it can bind to. This method is less time-consuming and resource intensive than the standard one.

Previously, it was thought that a plasmid had to have both the relaxase enzyme and the oriT sequence to bind to, but a bacterial cell can have an oriT region for conjugation to occur. With his new algorithm, he has been able to explore the DNA of 4600 plasmids from different bacteria found in nature.
– There may be eight times as many oriT regions than those discovered with standard methods.
– There may be twice as many mobile plasmids as previously known.
– There also may be twice as many bacterial species with mobile plasmids as previously known.
– More than half the plasmids have an oriT group matching to an enzyme for conjugation from a plasmid that already been classified in a different MOB group. This means that they could be transferred from a different plasmid in the same cell.

The last finding suggests that there may be far greater interchange between bacteria than had been previously been believed.

“This has been a major limitation of the research field up to now,” Zrimec said. “I hope that the methods will be able to benefit large parts of the research into antibiotic resistance, which is an extremely interdisciplinary and fragmented area. The methods can be used for studies aiming to develop more effective limitations to antibiotic use, instructions for how antibiotics are to be used, and new types of substances that can prevent the spread of resistance genes at the molecular level.”

Source: News-Medical.Net

Journal information: Zrimec, J. (2021) Multiple plasmid origin‐of‐transfer regions might aid the spread of antimicrobial resistance to human pathogens. MicrobiologyOpen.doi.org/10.1002/mbo3.1129.

New Type of Corneal Implant Fuses into the Eye

A new type of artificial cornea has been successfully implanted into an elderly patient, who demonstrated recovered sight the day after his surgery.

When the cornea is damaged by disease or injury, blindness can result, necessitating a cornea transplant. Artificial corneas are a much sought-after technology, as the normal treatment for a damaged cornea is to seek a transplanted replacement. However, for every 70 corneas sought, there is only a single donor cornea. CorNeat Vision is set to offer the first commercially available synthetic cornea implant, the KPro.

The new cornea has a clear centre section, surrounded by a white skirt consisting of electrospun nanofibres. Electrospun nanofibres have already found application in many medical applications, such as a new kind of translucent burn dressing. This skirt’s nanofibre material allows fibroblasts and collagen to infiltrate its structure, allowing full integration within a few weeks of surgery. This biomimetic technology results in faster healing times, the ability to use fully synthetic implants and is fully scalable as it does not rely on any harvested tissue.

The implantation procedure involves removing the epithelium covering the cornea, marking the location of where the artificial cornea implant should go, removing the cornea and then suturing its replacement into position.

Only a day after his surgery, the first recipient of this new artificial cornea was able to make out the faces of his relatives and read numbers off of a chart.

Source: Medical Xpress

UCT Expert Talks COVID and Warns of Third Wave

If South Africa does not pursue a rapid vaccination programme to achieve herd immunity, it may face a third wave as a consequence, warned a leading local expert.

Professor Marc Mendelson of UCT’s Division of Infectious Diseases and HIV Medicine at Groote Schuur Hospital made these statements while speaking during a virtual Summer School lecture on Saturday, titled “COVID-19 Insights and Lessons”.

“Without rapid vaccination of at least two thirds of the population, we [South Africa] are not going to get to population immunity, and without that, we will see another wave,” Mendelson warned.

However, he emphasised that much had been accomplished in the battle against COVID. “It is associated with a scientific endeavour that we have never seen before. We’re definitely better off a year down the line, but there are a huge number of things that we need to answer. As a country we still face deep problems with severe issues around vaccine strategy, and we haven’t even talked about vaccine denial,” he said.

Criticism has been directed at the South African government because of its failure to start a vaccination programme, despite its huge case load and status as Africa’s most wealthy nation. A leaked phone call from a Pfizer executive has only added to this, as it was revealed that for months SA health officials had not been responding to requests for vaccine discussions.

Regarding COVID transmission, he said that the virus resided in the upper respiratory tract as well as the lungs, and that it could be expelled in aerosol droplets. The clinical and epidemiological evidence suggested that larger, heavier droplets carried the virus.

“The household infection rates were high. A very large number of cases, the vast majority [in fact], were within families in close proximity [to one another]. This, epidemiologically, suggests that large droplets play a role in transmission.

“If you want to reduce transmission from large droplets, then you need to increase the distance you are from someone. Also, because droplets drop onto surfaces … you will need to clean surfaces and wash your hands well. This is the science behind the use of masks, handwashing, social distancing and ventilation.”

However, he added that a number of studies had found the virus in remote corners of hospitals at a distance from patients, suggesting that it had been carried there by smaller, aerosolised particles.

“If you want to reduce aerosols, one way of doing that is to improve ventilation. The more the air is changed, the [quicker] it will dilute small droplets,” he said.

Source: University of Cape Town

South African 510Y.V2 COVID Strain Resistant to Previous Antibodies

Results from a National Institute of Communicable Diseases (NICD) study shows that immunity gained against the initial strains of SARS-CoV-2 is blunted against the new 501Y.V2 strain that originated in South Africa.

The new variants which are more transmissible have mutations to their spike proteins that give the coronavirus its distinctive shape—and to which immune antibodies bind. Scientists have been concerned that the new strains may also escape vaccine containment, especially the E484K mutation, which has been observed in new strains found in Brazil and South Africa.

In the study, which is awaiting peer review, researchers took plasma from patients who had recovered from the original COVIDs, and tested those samples against the 501Y.V2 virus variant to measure antibody reaction. The virus was more resistant to these antibodies, which had been built up from previous infections. “Here we show that the 501Y.V2 lineage, which contains nine spike mutations and rapidly emerged in South Africa during the second half of 2020, is largely resistant to neutralising antibodies elicited by infection with previously circulating lineages,” said the researchers.

“This suggests that, despite the many people who have already been infected with SARS-CoV-2 globally and are presumed to have accumulated some level of immunity, new variants such as 501Y.V2 pose a significant re-infection risk.”

The researchers noted that these findings may have implications for those treated with convalescent plasma (a donor programme for which  is run by the South African National Blood Service). Additionally, there were “implications” for those vaccines that were developed based around an immune response to the virus’ spike proteins.

Vaccines may therefore have to be adjusted to account for the new spike mutation in order to retain effectiveness against variants possessing that mutation. The developers of the Oxford/AstraZeneca vaccine are already preparing to proactively adjust their vaccines to account for the new strains emerging around the world.

Commenting to the Science Media Centre, Lames Naismith, Director of the Rosalind Franklin Institute said that it was “not good news but it’s not unexpected.

“He said that real-world immune responses are more complicated than those of the blood plasma neutralising antibodies. “The vaccines do stimulate very strong responses, immunity is a sliding scale, it’s not an on/off switch,” he explained.

In another study posted online, it was reported that antibodies from recovered patients did mostly protect against B.1.1.7, the variant that originated in the UK.

“Our results suggest that the majority of vaccine responses should be effective against the B.1.1.7 variant,” concluded researchers from one the UK/Netherlands studies.

A separate study showed that the Pfizer/BioNTech vaccine also appeared to confer protection against that variant as well, with the authors concluding that it was “unlikely” that the B.1.1.7 variant could escape vaccine protection.

Source: Medical Xpress

High-carb and High-fat Diets Compared

Plant-based diets high in carbohydrates and meat-centred diets high in fats have become increasingly popular in recent years, and a new small, tightly controlled study has investigated their effects.

A myriad of health benefits ascribed to plant-based diets, while high-fat, low-carb diets have been proposed as a way to counteract overweight and diabetes risk. But there has been little understanding on how exactly the two diets compare, given that they restrict either fats or carbohydrates.

The answers to these questions were sought by a team at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).”High-fat foods have been thought to result in excess calorie intake because they have many calories per bite. Alternatively, high-carb foods can cause large swings in blood glucose and insulin that may increase hunger and lead to overeating,” said the study’s lead author, NIDDK Senior Investigator Kevin Hall, PhD. “Our study was designed to determine whether high-carb or high-fat diets result in greater calorie intake.”

The study took 11 male and 9 female non-diabetic participants and housed them in a facility for four weeks. For two weeks, they were served either a low-fat, high-carb, plant-based diet or a low-carb, high-fat meat-based diet. They were then changed to the other diet for the next two weeks. The food was minimally processed, contained equivalent amounts of non-starchy vegetables and participants were allowed snacks and to eat as much as they wanted.

The participants ate 550 to 700 fewer calories per day than when they ate the low-carb diet. Despite this difference, participants reported no hunger, and the same level of fullness and satisfaction with both diets. The participants lost weight on both diets, but more so on the low-fat diet.

“Despite eating food with an abundance of high glycemic carbohydrates that resulted in pronounced swings in blood glucose and insulin, people eating the plant-based, low-fat diet showed a significant reduction in calorie intake and loss of body fat, which challenges the idea that high-carb diets per se lead people to overeat. On the other hand, the animal-based, low-carb diet did not result in weight gain despite being high in fat,” Hall said.

The results add to a growing body of evidence that shows that diet is much more complex than just total calories. Hall’s previous research found that participants who ate highly processed food let to overeating and weight gain compared to a minimally processed carbs and fat-matched diet.

In this case, however, there were benefits observed in both diets.

“Interestingly, our findings suggest benefits to both diets, at least in the short-term. While the low-fat, plant-based diet helps curb appetite, the animal-based, low-carb diet resulted in lower and more steady insulin and glucose levels,” Hall commented. “We don’t yet know if these differences would be sustained over the long term.”

However, weight loss was not a goal of the study, and that may have influenced participants’ eating behaviours and the outcome of the study. The inpatient setting of the study also controlled what foods were available, unlike daily life where a variety of options, costs, preparation and availability concerns influence food choices. 

Source: Medical Xpress

WHO Warns of ‘Catastrophic Failure’ over COVID Vaccination

The World Health Organization head, Dr Tedros Adhanom Ghebreyesus, has warned that the world faces a “catastrophic moral failure” because of unequal access to COVID vaccines. 

He said that 49 wealthier states had conducted 39 million vaccinations between them, but one poor country had only 25 doses.

To date, the US, China, India, Russia and the UK have all developed vaccines, and mostly prioritised their own populations to receive them – although the German company BioNTech developed theirs in collaboration with Pfizer, and even so, the EU failed to secure vaccines sufficiently in advance

Dr Tedros spoke to an executive board session of the WHO, saying: “I need to be blunt: the world is on the brink of a catastrophic moral failure – and the price of this failure will be paid with lives and livelihoods in the world’s poorest countries.”

He warned that a selfish approach to vaccination would lead to hoarding and rising prices.

“Ultimately, these actions will only prolong the pandemic, the restrictions needed to contain it, and human and economic suffering,” he added.

Calling on nations to accelerate their progress, he said: “My challenge to all member states is to ensure that by the time World Health Day arrives on 7 April, Covid-19 vaccines are being administered in every country, as a symbol of hope for overcoming both the pandemic and the inequalities that lie at the root of so many global health challenges.” 

Thus far, 180 countries have signed on to the Covax initiative, which aims to negotiate as a bloc for lower vaccine prices. The initiative aims to distribute vaccines to low- and middle income countries, 92 of which will have their vaccines paid for by the initiative. Dr Tedros said that two billion doses had been secured, with an option of a billion more, with the first doses delivered by February.

UK Health Secretary Matt Hancock said in a reaction to Dr Tedros’ warnings that, “The UK is the world’s biggest supporter, financial supporter, of the global programme to ensure access to vaccines in all countries in the world.”

The UK has contributed £548m ($734m) to the Covax initiative. Canada drew criticism after it was revealed that, due to vaccine hoarding, the 70 poorest countries would only be able to vaccinate 10% of their population, while Canada had secured enough vaccines for five times its population of nearly 38 million. However, these vaccines are “hypothetical” according to Karina Gould, Canada’s minister of international development. Canada is also contributing $380 million to Covax. Furthermore, discussions are reportedly under way for South Africa to secure some of the vaccines allocated to Canada.

Source: BBC News

Coordination in Children Does Not Predict Aerobic Fitness

Even though clumsy children find it hard to perform as well in sports that require a lot of coordination, they are no less aerobically fit than their more agile peers.

This finding comes from a new study from the Faculty of Sport and Health Sciences of the University of Jyväskylä and the Institute of Biomedicine of the University of Eastern Finland. The general view is that children who have poor motor coordination tend to be overweight and have a low level of aerobic fitness – but this turns out not to be the case.

The study participants consisted of 332 children aged 7 to 11 years, with the study’s aim being to explore the association between aerobic fitness, body fat content, and motor skills. A maximum bicycle ergometer test was used to measure aerobic fitness and bioimpedance and DXA devices measured body composition. Common methods were used to gauge motor skills.

Eero Haapala, PhD, Faculty of Sport and Health Sciences, University of Jyväskylä, said: “Our study clearly demonstrated that aerobic fitness is not linked to motor skills when body composition is properly taken into account.”

She added: “Also, aerobic fitness was not strongly associated with overweight or obesity. Therefore, it seems that the role of poor aerobic fitness as a risk factor for poor motor skills and excess body weight has been strongly exaggerated.”

Earlier studies had shown that varied physical exercise can develop motor skills, regardless of body weight or aerobic fitness, and that less sedentary behaviour and more exercise protects against becoming overweight.

“The key message of our study is that even a child who is unfit can be motorically adept and the heart of a clumsier kid can be as fit as her or his more skilful peer,” Haapala concluded. “In addition, high levels of varied physical activity and reduced sedentary behaviour are central to the development of motor skills and the prevention of excess weight gain since childhood.”

Source: News-Medical.Net

Journal information: Haapala, EA, Gao, Y, Lintu, N, et al. Associations between cardiorespiratory fitness, motor competence, and adiposity in children. Transl Sports Med. 2021; 4: 56– 64. https://doi.org/10.1002/tsm2.198

Single Water Molecule Is the Key to Macrolide Resistance

High resolution molecular structures produced by researchers at the University of Illinois Chicago show that the effectiveness of the macrolides class of antibiotics – and bacterial resistance to it – depends on interaction with a single water molecule. 

Macrolides have a broad spectrum of use against most gram-positive bacteria and are a widely used treatment  for a variety of infections. Clarithromycin, for example, is used as a mainstay treatment for respiratory infections. Due to antibiotic overuse, antibiotic resistance has emerged Macrolides interrupt protein biosynthesis in the ribosomes of pathogenic bacteria, and are one of the most successful classes of antibiotics to use this mechanism of action. The macrolides accomplish this by entering the cell and binding to the bacteria’s ribosomes, preventing them from manufacturing and releasing new proteins. As a result of the halt in protein synthesis, the bacteria can no longer grow or replicate. However, mutations came about that rendered the bacteria resistant.

Seeking to understand how the bacteria came about their resistance, the researchers learned how to capture images of the ribosome and the macrolide invading it. The researchers discovered that precisely one water molecule was required for the antibiotic to bind to the ribosome.

Corresponding author Yury Polikanov, associate professor of biological sciences at UIC, said: “We compared the hi-res structures of the ribosomes from sensitive and resistant bacteria and noticed that a water molecule that is needed for the tight antibiotic binding was not present in the ribosomes from the drug-resistant bugs. In the ribosomes from the drug-resistant bacteria, there was simply no room for this water molecule.”

The mutation that conferred macrolide resistance adds a pair of methyl groups to where the macrolide molecule normally binds to the ribosome, and the water molecule instead disrupts the binding.  

“We are very much excited by this discovery,” Polikanov said. “Because we now know how exactly macrolide antibiotics interact with their target, the ribosome. This discovery is important because it will inform and facilitate the development of new antibiotics that do not need this water molecule for binding. There is a huge demand for such drugs that are able to kill even those bacteria that became resistant to the currently used drugs.”

Source: News-Medical.Net

Journal information: Svetlov, M.S., Syroegin, E.A., Aleksandrova, E.V. et al. Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance. Nat Chem Biol (2021). https://doi.org/10.1038/s41589-020-00715-0

Alcohol Linked to A High Proportion of Cancers

A new study shows that cancer is attributable to a significant proportion of cancer cases across the United States.

It is well known that alcohol is linked to cancers, but the state-level data shows for first time the impact of different levels of alcohol consumption and its cancer effects. This is also concerning for South Africa as the country has high rates of alcohol use, consuming 5 billion litres of alcohol annually, around 9 to 10 litres of pure alcohol for each individual (and likely more if sorghum beer is counted).

From data spanning 2013 to 2016, the percentage of cancer cases that are linked to alcohol ranged from a high of 6.7% in Delaware to a low of 2.9% in Utah. Following this pattern, Delaware also had the highest proportion of alcohol-related cancer deaths (4.5%) and Utah had the lowest (1.9%).
Farhad Islami, MD, PhD, and a team at the American Cancer Society, said: “This information is important for prioritising state-level cancer prevention and control efforts to reduce alcohol consumption and the burden of alcohol-related cancers.”

Alcohol use was more tightly linked to certain cancers: the proportion of oral cavity/pharyngeal cancer cases attributable to alcohol ranged from 36% in Utah to 62.5% in Delaware and was over 45% in all but five US states.

The majority of cases and deaths from the examined cancer types were found more in men, reflecting men’s higher consumption of alcohol.

Overall, alcohol was attributable to 8% of all cancer cases and 3.2% of cancer deaths. The American Cancer Society’s guideline for Diet and Physical Activity for Cancer Prevention states that it is best to abstain from alcohol entirely, and if not to limit drinks to 2 per day for men and 1 per day for women.

Source: Science Daily

Journal information: Ann Goding Sauer, Stacey A. Fedewa, Priti Bandi, Adair K. Minihan, Michal Stoklosa, Jeffrey Drope, Susan M. Gapstur, Ahmedin Jemal, Farhad Islami. Proportion of cancer cases and deaths attributable to alcohol consumption by US state, 2013-2016. Cancer Epidemiology, 2021; 71: 101893 DOI: 10.1016/j.canep.2021.101893