Day: August 11, 2023

Categories : Antibiotics GeneticsTags : Leave a comment

Genetic Mechanism Increases Resistance to the Antibiotic Albicidin by 1000-fold

On By ModernMedia
Photo by Sangharsh Lohakare on Unsplash

A new analysis shows that infectious bacteria exposed to the promising antibiotic albicidin rapidly develop up to a 1000-fold increase in resistance via a gene amplification mechanism. Mareike Saathoff of Freie Universität Berlin, Germany, and colleagues presented these findings in the open access journal PLOS Biology.

Bacterial resistance to antibiotics is a growing problem associated with millions of deaths around the world every year. Understanding how bacteria evolve resistance is key to developing more effective antibiotics and strategies for using them.

In recent years, albicidin has emerged as a promising antibiotic capable of killing a wide range of bacterial species by disrupting their DNA replication. Researchers are working to develop new albicidin-based medications; yet, despite its promise, some bacteria are able to develop resistance to albicidin.

To further investigate albicidin resistance mechanisms, Saathoff and colleagues conducted a suite of experiments employing a broad set of tools, including RNA sequencing, protein analysis, X-ray crystallography, and molecular modeling. They found that two bacteria often associated with human infection, Salmonella typhimurium and Escherichia coli, develop resistance to albicidin when exposed to increasingly higher concentrations of the compound. Their analysis narrowed down the source of this resistance to an increase in the number of copies of a gene known as STM3175 (YgiV) in the bacterial cells, which is amplified in each new generation of cells as they multiply. STM3175 encodes a protein that interacts with albicidin in such a way that protects the bacteria from it.

Further experiments showed that the same albicidin-resistance mechanism is widespread among both pathogenic and harmless bacteria, including the microbes Vibrio vulnificus, which can infect wounds, and Pseudomonas aeruginosa, which can cause pneumonia and other infections. These findings could help inform the ongoing development of albicidin-based antibiotic strategies.

The authors add, “Our study reveals a gene duplication and amplification-based mechanism of a transcriptional regulator in Gram-negative bacteria, that mediates resistance to the peptide antibiotic albicidin.”

Source: Science Daily

Categories : COVID HospitalsTags : Leave a comment

Nose-picking Healthcare Workers Were More Likely to Get COVID

On By ModernMedia
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A study of healthcare workers (HCW) found that those who picked their nose were more likely to get COVID than the people who refrained from such explorations. The Dutch researchers published their probing results in the journal PLOS One.

In the early stages of the COVID pandemic, researchers noted a wide range of efforts to prevent the spread of SARS-CoV-2, such as the wearing of personal protective equipment and maintaining social distancing, especially in the hospital setting. Much research went into the impacts of, eg, wearing glasses on the effectiveness of masking, but little if any attention was paid to a widespread but secretive habit.

Sikkens and colleagues retrospectively surveyed healthcare workers at Amsterdam University Medical Centers were in December 2021 about their behaviours during the first and second waves of the pandemic. They matched these responses were matched against prospectively collected COVID test results at the hospitals from March to October 2020. The nose pickers were nearly three times more likely to catch COVID (17.3% vs 5.9%) than those who refrained at all costs. Surprising results were found for those HCWs who owned up to the habit.

Secret nose pickers can take some comfort in that 85% of the cohort admitted that they picked their nose either daily, weekly, or monthly, and nose pickers tended to be younger. More men picked their nose (90%) than women (83%), and doctors were the most likely to be among the nose-picking offenders: 100% of residents admitted to it, along with 91% of specialists.

Sikkens et al. noted that one limitation of the study was that nose pickers were not asked about “the depth of penetration and eating of boogers”.

Other behaviours such nail biting, having a beard were not associated with COVID infection, nor was wearing glasses, though it showed a relevant trend. Interestingly, nose picking frequency was not linked to difference in COVID infection risk; 27% of those who reported monthly picking, 35% among weekly pickers, and 32% of daily pickers.

Frequency of nose picking did not appear to be linked with any difference in COVID infection risk, with positive cases in 27% of those who reported monthly picking, 35% among weekly pickers, and 32% of daily pickers. No participants reported picking their nose every hour, thankfully.

One-third of the cohort reported nail biting, two-thirds wore glasses, and 31% of the men had beards.

A study strength was that SARS-CoV-2 positivity was determined by prospective longitudinal serological sampling, though this may not be generalisable to the current era of vaccines and circulating Omicron variants. The retrospective nature of the survey may have introduced recall bias.

Sikken et al. noted that it is surprising that SARS-CoV-2 transmission routes had been so thoroughly researched, yet simple behaviours had been overlooked. “Possibly this sensitive subject is still taboo in the health care profession. It is commendable we assume HCWs to not portray bad habits, yet we too are only human after all, as illustrated by the pivotal proportion of nose pickers in our cohort (84.5%).”

Categories : Diseases, Syndromes and ConditionsTags : Leave a comment

Inflammation Impedes the Development of Malaria Parasites

On By ModernMedia
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Researchers have found that inflammation can slow down the development of malaria parasites in the bloodstream, which may lead to a new strategy for preventing or limiting severe disease.

The malaria-causing Plasmodium parasites invade and multiply within red blood cells. Studies have shown that the parasites can rapidly sense and respond to conditions within the host by intimately syncing with their internal body clocks. While it is known that the body’s nutrient levels and daily circadian rhythms affect the parasites’ development, little was known about the impact of host inflammation on the parasites.

This animal-model study, led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and the Kirby Institute and published in the journal mBio, reveals that when the body’s immune system responds to inflammation it alters the plasma’s chemical composition, directly impeding the maturation of the Plasmodium parasites in the bloodstream.

University of Melbourne’s Associate Professor Ashraful Haque, a senior author of the paper, said this work highlights the captivating dynamic of the host-parasite relationship.

“First, we discovered that inflammation in the body prevented the early stage of the parasites from maturing. We also noticed that inflammation triggered significant changes in the composition of the plasma – we were actually quite surprised by the magnitude of these changes,” said Associate Professor Haque.

“As we dug deeper, we found substances in the altered plasma that, we believe, are what may inhibit parasite growth in the body. This work reveals a new mechanism that slows down the malaria parasite’s development in the bloodstream. Our research was done using animal models, so it would be really interesting to study if such inhibitory mechanisms occur in humans too.”

Dr David Khoury, co-senior author of the paper, said the scientists found a remarkable response by the parasites to the changes in their environment.

“Parasites residing in red blood cells rapidly sense and respond to their new environment, showing fascinating adaptability. Using cutting-edge genome sequencing technology, we observed that even after just four hours in this changed plasma, the parasites adjusted their genetic and protein activity, resulting in slower maturation within red blood cells. It’s almost like the parasites actively sense an inhospitable host environment, and as a result trigger a coping mechanism,” said Dr Khoury.

“We believe this is the first study to show that inflammation can change how individual parasites behave genetically in the body.”

Professor Miles Davenport, co-senior author of the paper, said this work on the interaction between systemic host inflammation and malaria parasite maturation offers several potential benefits.

“This study, while based on animal models, broadens our understanding of malaria. It provides a foundation for further investigations into the specific mechanisms involved in the modulation of parasite maturation by inflammation, and opens avenues for future studies to explore the identified inhibitory factors, genetic changes and their implications for malaria development,” said Professor Davenport.

Source: The Peter Doherty Institute for Infection and Immunity

Categories : Cancer Diet and NutritionTags : Leave a comment

Study Shows a Link Between Sugar-sweetened Beverages and Liver Cancer

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One of the first studies to look at the association between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality, has found an 85% increase in liver cancer incidence between postmenopausal women who consume one sweetened drink per day and those who consume them rarely. Results from the study, which was led by Brigham and Women’s Hospital, are published in JAMA.

“To our knowledge, this is the first study to report an association between sugar sweetened beverage intake and chronic liver disease mortality,” said first author Longgang Zhao, PhD, of the Brigham’s Channing Division of Network Medicine. Zhao is a postdoctoral researcher who works with senior author Xuehong Zhang, MBBS, ScD, in the Channing Division. “Our findings, if confirmed, may pave the way to a public health strategy to reduce risk of liver disease based on data from a large and geographically diverse cohort.”

This observational study included nearly 100 000 postmenopausal women from the large, prospective Women’s Health Initiative study. Participants reported their usual soft drink, fruit drink (not including fruit juice) consumption, and then reported artificially sweetened beverage consumption after three years. Participants were followed for a median of more than 20 years. Researchers looked at self-reported liver cancer incidence and death due to chronic liver disease such as fibrosis, cirrhosis, or chronic hepatitis, which were further verified by medical records or the National Death Index.

A total of 98 786 postmenopausal women were included in the final analyses. The 6.8% of women who consumed one or more sugar-sweetened beverages daily had an 85% higher risk of liver cancer and 68% higher risk of chronic liver disease mortality compared to those who had fewer than three sugar sweetened beverages per month. No such increase was observed for consumption of artificially-sweetened beverages.

The authors note that the study was observational, and causality cannot be inferred, and relied on self-reported responses about intake, sugar content and outcomes. More studies are needed to validate this risk association and determine why the sugary drinks appeared to increase risk of liver cancer and disease. Furthermore, more research is needed to elucidate the potential mechanisms by integrating genetics, preclinical and experimental studies, and -omics data.

Source: Mass General Brigham