This is how the superbug Pseudomonas aeruginosa reacts to antibiotics

The bacterium Pseudomonas aeruginosa is resistant to all antibiotics on the market. Therefore, there is a great need for new therapeutic approaches. In order to find them, it helps to understand how the germ reacts to active substances.
Researchers at Ruhr-Universität Bochum (RUB) have studied how different drugs affect the difficult-to-treat bacterium Pseudomonas aeruginosa. According to the World Health Organisation, new treatment options for the pathogen are urgently required, as some strains are already resistant to all currently approved antibiotics. The Bochum-based team headed by Professor Julia Bandow exposed P. aeruginosa to various substances and observed their effects on the protein make-up of the bacteria, also known as the proteome. The results enable the researchers to conclude what makes P. aeruginosa resistant; in addition, new approaches for treatment of the priority pathogen were investigated. Together with the group of Professor Pei Zhou from Duke University in the USA, the RUB team describes the analyses in “Antimicrobial Agents and Chemotherapy,” a journal of the American Society for Microbiology, published online on 8 November 2021.
Bacteria are often categorised as either Gram-positive or Gram-negative depending on how they react in a certain staining procedure, namely the Gram stain. “Infections with the Gram-negative pathogen Pseudomonas aeruginosa are feared as being difficult to treat,” says Julia Bandow, head of the Applied Microbiology research group at RUB. Patients can become infected with the germ in hospitals, for example; it causes pneumonia or sepsis, which can be fatal.
Specific properties might become targets for drugs
Gram-negative bacteria have a number of properties that are different from those of Gram-positive bacteria. For example, they produce sugar-lipid compounds that are characteristic for their outer membranes. “Some of the specific properties of Gram-negative bacteria could provide attractive targets for antibiotics,” says Bandow. “This is what we seek to exploit.”
In the first step, the researchers investigated why P. aeruginosa is resistant to so many common antibiotics. They treated the germ with twelve different approved antibiotics and documented the resulting changes in the proteome. This allowed them to deduce how the cells defend themselves against the antibiotics. The team also divided the individual substances into groups based on how similar the triggered effects were. This correlated with similarities in the compounds’ modes of action.
Furthermore, the scientists tested the experimental substance CHIR-090. Compared to the effects of approved antibiotics, CHIR-090 produced a unique proteome response. CHIR-090 blocks the production of sugar-lipid compounds addressing a target that has not yet been exploited clinically. No resistance to the drug has been observed in clinically relevant bacterial strains. “Resistance to new classes of substances is expected to emerge more slowly than to derivatives of conventional antibiotics,” explains Julia Bandow.
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Materials provided by Ruhr-University Bochum. Note: Content may be edited for style and length.

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Scientists produce new antibiotics by gene editing

Scientists have discovered a new route to produce complex antibiotics exploiting gene editing to re-programme pathways to future medicines urgently required to combat antimicrobial resistance, treat neglected diseases and prevent future pandemics.
Researchers from The University of Manchester have discovered a new way of manipulating key assembly line enzymes in bacteria which could pave the way for a new generation of antibiotic treatments.
New research published today in Nature Communications, describes how CRISPR-cas9 gene editing can be used to create new nonribosomal peptide synthetase (NRPS) enzymes that deliver clinically important antibiotics. NRPS enzymes are prolific producers of natural antibiotics such as penicillin. However, up until know, manipulating these complex enzymes to produce new and more effective antibiotics has been a major challenge.
The problem of antimicrobial resistance
The UK government suggest, antimicrobial resistance (AMR) infections are estimated to cause 700,000 deaths each year globally and are predicted to rise to 10 million, costing the global economy $100 trillion, by 2050. AMR also threatens many of the UN’s Sustainable Development Goals (SDGs), with an extra 28 million people that could be forced into extreme poverty by 2050 unless AMR is contained.
The Manchester team says the gene editing process could be used to produce improved antibiotics and possibly lead to the development of new treatments helping in the fight against drug-resistant pathogens and illnesses in the future. Jason Micklefield, Professor of Chemical Biology at the Manchester Institute of Biotechnology, UK, explains: “The emergence of antibiotic-resistant pathogens is one of the biggest threats we face today.”
“The gene editing approach we developed is a very efficient and rapid way to engineer complex assembly line enzymes that can produce new antibiotic structures with potentially improved properties.”
The potential of nonribosomal peptide antibiotics
Microorganisms in our environment, such as soil dwelling bacteria, have evolved nonribosomal peptide synthetase enzymes (NRPS) that assemble building blocks called amino acids into peptide products which often have very potent antibiotic activity. Many of the most therapeutically important antibiotics, used in the clinic today, are derived from these NRPS enzymes (e.g. penicillin, vancomycin and daptomycin).
Unfortunately, deadly pathogens are emerging which are resistant to all of these existing antibiotic drugs. One solution could be to create new antibiotics with improved properties that can evade the resistance mechanisms of the pathogens. However, the nonribosomal peptide antibiotics are very complex structures which are difficult and expensive to produce by normal chemical methods. To address this, the Manchester team use gene editing to engineer the NRPS enzymes, swapping domains that recognise different amino acid building, leading to new assembly lines that can deliver new peptide products.
Micklefield added: “We are now able to use gene editing to introduce targeted changes to complex NRPS enzymes, introducing alternative amino acids precursors into peptide structures. We are optimistic that our new approach could lead to new ways of making improved antibiotics which are urgently needed to combat emerging drug-resistant pathogens.”
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Study links increasing air pollution to the rise of a type of lung cancer

An international team of scientists, led by Nanyang Technological University, Singapore (NTU Singapore), has linked increased air pollution to an uptick in cases of lung adenocarcinoma (LADC) worldwide. The same study also concluded an overall lower consumption of tobacco worldwide is statistically linked to less people contracting lung squamous cell carcinoma (LSCC).
Lung adenocarcinoma is a type of cancer for which research strongly suggests that genetic, environmental, and lifestyle factors play a part, while lung squamous cell carcinoma is often linked to a history of smoking.
This study, done in collaboration between NTU and the Chinese University of Hong Kong, showed that a 0.1 micrograms per cubic metre (μg/m3) increment of black carbon[1], also known as soot, in the Earth’s atmosphere, is associated with a 12 per cent increase in LADC incidence globally.
Black carbon is a pollutant that is classified as under PM2.5[2], and the research team found that it has increased globally by 3.6 μg/m3 yearly from 1990 to 2012.
Meanwhile, a one per cent decline of smoking prevalence was associated with a nine per cent drop in LSCC incidence globally. The number of smokers worldwide decreased by 0.26 per cent a year, cumulatively falling by nearly six per cent from 1990 to 2012.
Lung cancer remains the leading cause of cancer with an estimated 1.8 million deaths in 2020, according to CA: A Cancer Journal for Clinicians[3]. Global statistics have highlighted the trends of lung cancers, but understanding what may be causing them has been unclear, until the NTU-led study, which has associated the incidence of the cancers to tobacco consumption and air pollution.

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Spicy breast milk?

Breast milk is the first food that babies consume. Various studies have suggested that the “taste experience” in early childhood influences eating behavior in adults. Unlike standardized infant formula, natural milk does not taste and smell the same every day. The differences are largely due to the maternal diet.
No one-to-one transfer
However, the taste and aroma of food consumed by the mother are not transferred one-to-one to her milk. Research has already shown that odor and taste active substances from garlic or coffee partly enter the mother’s milk as an odor active metabolic product, while flavors from fish oil or nursing tea were of little to no significance in this respect.
The extent to which pungent substances from chili, ginger, or pepper are found in breast milk has been even less researched than aroma and taste substances. For this reason, a scientific team led by TUM has now investigated whether these substances are transferred from food to breast milk and if so, which ones.
Piperine detectable after just one hour
Through extensive mass spectrometric analyses, the team has shown that already one hour after consumption of a standardized curry dish, piperine is detectable in breast milk for several hours. “The observed maximum concentrations of 14 to 57 micrograms per liter were about 70- to 350-fold below the taste perception threshold of an adult,” says Professor Corinna Dawid, who heads the Chair of Food Chemistry and Molecular Sensory Science at TUM commissarial for Professor Thomas Hofmann.
Roman Lang, who was initially involved in the study as a scientist at TUM and later at the Leibniz Institute for Food Systems Biology (LSB) adds, “It seems rather unlikely to us that the infants consciously perceive the sharpness. Nevertheless, it is conceivable that regular, low-threshold activation of the “pungent receptor” TRPV1 could help to increase tolerance for such substances later on.”
Pungents from ginger or chili as well as the secondary plant compound curcumin, which is also abundant in curry, did not enter milk, according to the research. “We were particularly surprised by the latter, since piperine is supposed to significantly increase the bioavailability of curcumin according to the results of other studies,” reports Roman Lang, who heads the Biosystems Chemistry & Human Metabolism research group at the LSB.
“These observations were made in collaboration with our partners from the Friedrich-Alexander-University Erlangen-Nuremberg, the Fraunhofer Institute for Process Engineering and Packaging IVV, and the LSB. Continued exploration will help us to better understand both the emergence of food preferences and the metabolic processes that play a role in the transfer of bioactive food ingredients into breast milk,” says TUM-Professor Corinna Dawid.
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Materials provided by Technical University of Munich (TUM). Note: Content may be edited for style and length.

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Statin use affects prostate cancer screening results

Prostate cancer screening results differ in men taking cholesterol-lowering statin drugs compared with non-users, a study conducted at Tampere University in Finland finds. In statin users, screening did not increase the incidence of prostate cancer as it did in other men.
The study found the clearest difference in low-risk cancer, which is often overdiagnosed due to screening. The number of low-risk tumours found in screening was significantly lower in statin users. However, statin use caused no difference in the detection of high-risk cancers. In the screened group, prostate cancer mortality was slightly lower than in the unscreened group, both in men taking statins and other men.
“The study provides significant new information because statin use is very common and the effects of prostate cancer screening have not been previously evaluated in relation to statin use,” says Professor Teemu Murtola from the Faculty of Medicine and Health Technology at Tampere University.
The study was published in the JAMA Oncology journal on 24 November 2021.
The findings may be explained by the fact that statin use improves the accuracy of prostate cancer screening. This means that screening detects dangerous types of cancer in these men as well as in others, but in statin users, there is less of the so-called overdiagnosis, which means the detection of low-risk prostate cancers that do not pose a health threat due to their very slow growth rate.
Another possible explanation could be that men who use statins are a select group who already actively use health services and have had PSA tests outside systematic screening. In those cases, the additional screening done in the study does not have such a great impact.
The study was based on data from the Finnish Prostate Cancer Screening Trial which started in 1996-1999. A total of about 80,000 men were included in the study, of whom just under 32,000 were screened with the PSA test every four years. The project was carried out jointly by Tampere University and the University of Helsinki and the Helsinki and Tampere University Hospitals.
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Breakthrough in understanding motor neuron disease

Researchers at Trinity College Dublin have made a major discovery in understanding motor neuron disease (MND). The research team has found that MND has 4 distinct patterns of changes in electrical signals that can be identified using EEG (electroencephalography).
This breakthrough will be extremely valuable in identifying patients for clinical trials and will assist in finding new treatments for this devastating disease.
The study has been published online today (Monday, 22nd November 2021) in the journal Brain.
MND is a devastating condition which causes progressive paralysis, changes in thinking, increasing physical disability and ultimately death within an average of two to three years. There are over 500 people in Ireland with MND, and one person is diagnosed every 3 days with the condition. There is currently no effective treatment.
While trials of new drugs are being undertaken, MND is known to be very heterogeneous with different patterns of disability and life expectancy. Predicting in advance the pattern of disability and life expectancy is one of the major challenges in designing modern clinical trials.
The world class electrical signal analysis research developed within Trinity College has discovered different patterns of brain network disruption reflect the underlying disease process. The Trinity researchers have now shown that these patterns of brain network disruptions in MND cluster into 4 distinct subtypes that are predictive of how the disease progresses. The team’s findings move the Trinity researchers one step closer to building better and more effective treatments for different sub-categories of the disease.
The work was performed by Mr Stefan Dukic, a PhD student within the Academic Unit of Neurology at Trinity, under the supervision of Dr Bahman Nasseroleslami, Fr Tony Coote Assistant Professor in Neuroelectric Signal Analysis.
Dr Bahman Nasseroleslami said:
Understanding how brain networking is disrupted in MND has been the focus of our research for the past 10 years. This work show that we are on the right track, and that the technologies we have developed to capture electrical activity in the brain can identify important differences between different patient groups.
Professor Orla Hardiman, Professor of Neurology and a world leader in MND research said:
This is a very important and exciting body of work. A major barrier to providing the right drug for the right patient in MND is the heterogeneity of the disease. This breakthrough research has shown that it is possible to use patterns of brain network dysfunction to identify subgroups of patients that cannot be distinguished by clinical examination. The implications of this work are enormous, as we will have new and reliable ways segregate patients based on what is really happening within the nervous system in MND.
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First study of its kind to investigate a high priority but little known pathogen found in Irish hospitals

First study of its kind to investigate a high priority but little known pathogen found in Irish hospitals: Trinity research
By understanding the epidemiology and population biology of a significant and high-priority pathogen, Enteroccocus faecium (E. faecium) in Irish hospitals, researchers from Trinity College and colleagues are, for the first time, providing the evidence base for more effective surveillance, and infection and prevention control strategies aimed at minimising the spread of the antibiotic resistant bacteria (Thursday, 18th November 2021).
The study has been published in the international Journal of Antimicrobial Chemotherapy and funded by the Health Research Board (HRB).
Enteroccocus faecium (E. faecium) has been described by the World Health Organisation as a high priority pathogen in urgent need of drug research and development. E. faecium is intrinsically resistant to a range of commonly used antibiotics and treatment options are limited. Vancomycin is one of the few antibiotics that is effective for treatment, however the incidence of vancomycin resistance is rising worldwide including in Ireland, further limiting treatment options.
Data from the European Centre for Disease Prevention and Control revealed that for over a decade, the Republic of Ireland has reported one of the highest rates of vancomycin resistance among invasive E. faecium infections in Europe.
Vancomycin resistant E. faecium (VREfm) bacteria have become a significant cause of infection in hospitals worldwide, particularly in vulnerable and immunocompromised individuals. Many studies of VREfm have been reported from other countries globally, but this investigation marks the first such study from Ireland.

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A Heart-Healthy Way to Eat

Aim for an overall healthful dietary pattern, the American Heart Association advises, rather than focusing on “good” or “bad” foods.There are no “good” foods and “bad” foods. Rather, it’s your overall dietary pattern that matters most when it comes to healthful eating.That’s the main message from the American Heart Association in its latest nutrition guidelines to improve the hearts and health of Americans of all ages and life circumstances.The experts who wrote the guidelines recognize that people don’t eat nutrients or individual ingredients. They eat foods, and most people want to enjoy the foods they eat while staying within their budgets and, the association hopes, without injuring their bodies.This doesn’t mean you need to totally avoid Big Macs, Cokes and French fries, but it does mean you should not regularly indulge in such fare if you want to stay healthy.Dr. Robert H. Eckel, a former president of the American Heart Association, and an endocrinologist and lipid specialist at the University of Colorado Denver, told me he “occasionally” indulges in foods outside a wholesome dietary pattern. The operative word here, though, is “occasionally.”Dr. Neil J. Stone, a preventive cardiologist at the Feinberg School of Medicine at Northwestern University, who praised the thoughtfulness and expertise of the guidelines committee, said in an interview, “There’s no such thing as one diet that fits all, but there are principles to form the basis of diets that fit everyone.”He added: “The goal is to make good nutrition possible for all. The healthier we can keep everybody in this country, the lower our health costs will be.”In the 15 years since the heart association last issued dietary guidelines to reduce the risk of cardiovascular disease, almost nothing has changed for the better. The typical American diet has remained highly processed. Americans consume too much added sugars, artery-clogging fats, refined starches, red meat and salt and don’t eat enough nutrient-rich vegetables, fruits, nuts, beans and whole grains that can help prevent heart disease, diabetes and cancer.But rather than become discouraged, the association decided to try a different approach. For too long, nutrition advice has been overly focused on individual nutrients and ingredients, Alice H. Lichtenstein, the guidelines’ chief author, told me, and it hasn’t been focused enough on overall dietary patterns that can best fit people’s lives and budgets.So instead of a laundry list of “thou shalt not eats,” Dr. Lichtenstein said, the association’s committee on nutrition and cardiovascular disease chose to promote heart-healthy dietary patterns that could suit a wide range of tastes and eating habits. In avoiding “no noes” and dietary revolutions, the new guidelines can foster gradual evolutionary changes meant to last a lifetime.The committee recognized that for people to adopt and stick to a wholesome dietary pattern, it should accommodate personal likes and dislikes, ethnic and cultural practices and life circumstances, and it should consider whether most meals are consumed at home or on the go.For example, rather than urging people to skip pasta because it’s a refined carbohydrate, a more effective message might be to tell people to eat it the traditional Italian way, as a small first-course portion. Or, if pasta is your main course, choose a product made from an unrefined carbohydrate like whole wheat, brown rice or lentils.“We’re talking about lifelong changes that incorporate personal preferences, culinary traditions and what’s available where people shop and eat,” said Dr. Lichtenstein, a professor of nutrition science and policy at the Friedman School at Tufts University. “The advice is evidence-based and applies to everything people eat regardless of where the food is procured, prepared and consumed.”The guidelines’ first principle is to adjust one’s “energy intake and expenditure” to “achieve and maintain a healthy body weight,” a recommendation that may be easier to follow with the next two principles: Eat plenty of fruits and vegetables, and choose foods made mostly with whole grains rather than refined grains. If cost or availability is an issue, as is the case in many of the country’s food deserts where fresh produce is scarce, Dr. Lichtenstein suggested keeping bags of frozen fruits and vegetables on hand to reduce waste, add convenience and save money.Some wholesome protein choices that the committee recommended included fish and seafood (although not breaded and fried), legumes and nuts, and low-fat or fat-free dairy products. If meat is desired, choose lean cuts and refrain from processed meats like sausages, hot dogs and deli meats that are high in salt and saturated fat.The committee’s advice on protein foods, published during the climate talks in Glasgow, was well-timed. Choosing plant-based proteins over animal sources of protein not only has health value for consumers but can help to foster a healthier planet.Experts have long known that animal products like beef, lamb, pork and veal have a disproportionately negative impact on the environment. Raising animals requires more water and land and generates more greenhouse gases than growing protein-rich plants does.“This is a win-win for individuals and our environment,” Dr. Lichtenstein said. However, she cautioned, if a plant-based diet is overloaded with refined carbohydrates and sugars, it will raise the risk of Type 2 diabetes and heart disease. And she discouraged relying on popular plant-based meat alternatives that are ultra-processed and often high in sodium, unhealthy fats and calories, and that “may not be ecologically sound to produce.”To protect both the environment and human health, the committee advised shifting one’s diet away from tropical oils — coconut, palm and palm kernel — as well as animal fats (butter and lard) and partially hydrogenated fats (read the nutrition label). Instead, use liquid plant oils like corn, soybean, safflower, sunflower, canola, nut and olive. They have been shown to lower the risk of cardiovascular disease by about 30 percent, an effect comparable to taking a statin drug.As for beverages, the committee endorsed the current national dietary guideline to avoid drinks with added sugars (including honey and concentrated fruit juice). If you don’t currently drink alcohol, the committee advised against starting; for those who do drink, limit consumption to one to two drinks a day.All told, the dietary patterns that the committee outlined can go far beyond reducing the risk of cardiovascular diseases like heart attacks and strokes. They can also protect against Type 2 diabetes and a decline of kidney function, and perhaps even help foster better cognitive abilities and a slower rate of age-related cognitive decline.The earlier in life a wholesome dietary pattern begins, the better, Dr. Lichtenstein said. “It should start preconception, not after someone has a heart attack, and reinforced through nutrition education in school, K through 12.”And during annual checkups, Dr. Eckel said, primary care doctors should devote three to five minutes of the visit to a lifestyle interview, asking patients how many servings of fruits, vegetables and whole grains they consume and whether they read nutrition labels.

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Omicron: Australia pauses next phase of border reopening

SharecloseShare pageCopy linkAbout sharingImage source, ReutersAustralia has paused plans to reopen its borders to some foreign nationals amid fears over the new Covid variant.The country was due to allow vaccinated skilled migrants and international students entry from 1 December.But Prime Minister Scott Morrison said a delay of a fortnight was “necessary” following Omicron’s discovery.The heavily mutated variant was detected in South Africa earlier this month, with initial evidence suggesting it has a higher re-infection risk.It prompted the UK, EU and US to issue a travel ban on Southern African countries – a decision criticised by South Africa’s President Cyril Ramaphosa.Japan announced on Monday that all foreigners would be banned from entering as a result of the variant, which the World Health Organization (WHO) has said poses a high risk globally.Prime Minister Fumio Kishida did not say how long the measures would last, and told reporters that he was ready to face criticism for being too cautious. “These are temporary, exceptional measures that we are taking for safety’s sake, until there is clearer information about the Omicron variant,” Mr Kishida said. Japan has yet to detect any cases. The battle to open up ‘Fortress Australia’Watch: Emotional reunions as Australia’s border reopensAustralia – which has so far found five Omicron infections among travellers arriving in the country – has not announced rolling back any of the restrictions it had already eased.The country has until recently had some of the strictest border policies in the world, barring even its own people from leaving the country under a strategy sometimes dubbed “Fortress Australia”.The policy was praised for helping to control Covid, but it has also controversially separated families.The measure was only eased in November this year, giving long-awaited freedoms to vaccinated citizens and their relatives. Under the current rules, permanent residents and fully vaccinated travellers from New Zealand and Singapore are allowed into Australia.The relaxation of rules planned for 1 December would have added fully vaccinated Japanese and South Korean citizens to the list of those who could enter, as well as eligible visa holders.But Australia’s National Security Committee said the pause was necessary as it would allow them to consider issues like “the efficacy of the vaccine” and the impact of the variant.

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