Now, Johns Hopkins Medicine scientists say they have shed new light on how bacteria protect themselves from certain phage invaders — by seizing genetic material from weakened, dormant phages and using it to “vaccinate” themselves to elicit an immune response.

In their experiments, the scientists say Streptococcus pyogenes bacteria (which cause strep throat) take advantage of a class of phages known as temperate phages, which can either kill cells or become dormant. The bacteria steal genetic material from temperate phages during this dormant period and form a biological “memory” of the invader that their offspring inherit as the bacteria multiply. Equipped with these memories, the new population can recognize these viruses and fight them off.

A report on the experiments, supported in part by the National Institutes of Health, was published March 12 in the journal Cell Host & Microbe. The findings help scientists better understand how bacterial cells that cause serious diseases, including Staph and E. coli infections and cholera, become toxic to humans — a process that involves toxic genes expressed by otherwise dormant phages that reside within the bacterial cell, says corresponding author Joshua Modell, Ph.D., associate professor of molecular biology and genetics at the Johns Hopkins University School of Medicine.

“We essentially wanted to answer the question: If bacterial cells don’t have any memory, or survival skills, to combat a new temperate phage that shows up, how do they buy themselves enough time to establish a new memory, before they succumb to that initial infection?” says Modell.

The Johns Hopkins investigators say bacteria have long been known to use CRISPR-Cas systems to chop up phage DNA, break it down and get rid of it. Crucially, CRISPR systems can only destroy DNA that matches a “memory” captured from a prior infection and stored within the bacteria’s own genome, say the researchers. In this way, the CRISPR system acts as a recording device that documents the long list of foreign invaders encountered by a particular bacterial strain.

To conduct their research, the scientists say they infected populations of bacteria with naturally occurring phages that go dormant or genetically engineered non-dormant phages in separate flasks that contained millions of bacterial cells.

“Our results indicate that the bacteria’s CRISPR system was more effective at using the naturally dormant phage to pull parts of the viral genetic code into their genome,” says Modell. “When we tested phages that could not go dormant, the CRISPR system did not work nearly as well.”

After isolating the bacteria that survived, and letting the survivors repopulate the flask, the scientists used genome sequencing to catalog hundreds of thousands of new DNA memories that the CRISPR Cas9 system had created from the test phages, honing in on those that contribute to cell immunity. The scientists also determined that bacteria created those memories during the temperate phage’s dormancy period, when it did not pose a threat to the population.

“This is conceptually similar to a vaccine with an attenuated virus,” says Nicholas Keith, a graduate student and first author of the paper. “We believe this is the reason why the CRISPR Cas9 system has a unique relationship with this specific class of temperate phage.”

“We can use these types of experiments to find what elements of the phage, the bacterial host and its CRISPR system are important for all stages of bacterial immunity,” Keith says.

In future experiments, the scientists aim to learn more about how CRISPR systems protect bacteria cells from viruses that don’t go dormant, Modell says.

“We know CRISPR systems are one of the first lines of defense against the transfer of hazardous genes from phages that turn bacterial cells toxic,” says Modell. “Furthermore, our studies will inform the design of ‘phage therapies’ which could be used in clinical cases where a bacterial infection is resistant to all available antibiotics.”

In addition to Keith and Modell, study contributors are Rhett Snyder from Johns Hopkins and Chad Euler from Hunter College.

The research was funded by the Johns Hopkins University School of Medicine, the National Institutes of Health National Institute of General Medical Sciences (R35GM142731), the Rita Allen Foundation and the National Science Foundation.

New research from the University of Chicago shows how a specially trained population of immune cells keeps the peace by preventing other immune cells from attacking their own. The study, published in Science, provides a better understanding of immune regulation during infection and could provide a foundation for interventions to prevent or reverse autoimmune diseases.

Several groups of white blood cells help coordinate immune responses. Dendritic cells take up proteins from foreign pathogens, chop them up into peptides called antigens, and display them on their surface. CD4+ conventional T (Tconv) cells, or helper T cells, inspect the peptides presented by dendritic cells. If the peptides are foreign antigens, the T cells expand in numbers and transform into an activated state, specialized to eradicate the pathogen. If the dendritic cell is carrying a “self-peptide,” or peptides from the body’s own tissue, the T cells are supposed to lay off.

During an autoimmune response, the helper T cells don’t distinguish between foreign peptide antigens and self-peptides properly and go on the attack no matter what. To prevent this from happening, another group of T cells called CD4+ regulatory T (Treg) cells, are supposed to intervene and prevent friendly fire from the Tconv cells.

“You can think of them [Treg cells] as peacekeeper cells,” said Pete Savage, PhD, Professor of Pathology at UChicago and senior author of the new study. Tregs obviously do their job well most of the time, but Savage said that it has never been clear how they know when to intervene and prevent helper T cells from starting an autoimmune response, and when to hold back and let them fight an infection.

So, Savage and his team, led by David Klawon, PhD, a former graduate student in his lab who is now a postdoctoral fellow at MIT, wanted to explore this property of the immune system, known in the field as self-nonself discrimination. T cells are produced in the thymus, a specialized organ of the immune system. During development, Treg cells are trained to recognize specific peptides, including self-peptides from the body. When dendritic cells present a self-peptide, the Treg cells trained to spot them intervene to stop helper T cells from getting triggered.

This specificity is what Savage’s team found makes a crucial difference in self-nonself discrimination. The researchers experimentally depleted Treg cells in mice that were specific to a single self-peptide from the prostate. In healthy mice in the absence of infection, this change did not trigger autoimmunity to the prostate. When the researchers infected mice with a bacterium that expressed the prostate self-peptide, however, the absence of matched, prostate-specific Treg cells triggered prostate-reactive T helper cells and introduced autoimmunity to the prostate.

Interestingly though, this alteration did not impair the ability of helper T cells to control the bacterial infection by responding to foreign peptides.

“It’s like a doppelganger population of T cells. The CD4 helper cells that could induce disease by attacking the self share an equivalent, matched population of these peacekeeper Treg cells,” Savage said. “When we removed Treg cells reactive to a single self-peptide, the T helper cells reactive to that self-peptide were no longer controlled, and they induced autoimmunity.”

The root causes of autoimmune disease are a complex interaction of genetics, the environment, lifestyle, and the immune system. Classic, conventional thinking in the immunology field promoted the idea that the immune system establishes self-nonself discrimination by purging the body of helper T cells that are reactive to self-peptides, thereby preventing autoimmunity. Savage said this study shows that purging is inefficient though, and that specificity matching by Treg cells may be equally as important.

“The idea is that specificity matters, and for a fully healthy immune system, you need to have a good collection of these doppelganger Treg cells,” he said. As long as the immune system generates enough matched Treg cells, they can prevent autoimmune responses without impacting responses to infections.

“It’s like flipping the idea of self-nonself discrimination upside down. Instead of having to delete all helper T cells reactive to self-antigens, you simply generate enough of these Treg peacekeeper cells instead,” Savage said.

Analysis built on national studies from Germany, Australia, the United Kingdom, and the Netherlands

It is a common fact that satisfaction in a romantic relationship declines over time. This reduction in satisfaction is particularly marked in the first years of a relationship, and a distinctive low point is often reached after a period of ten years. Instead of considering the processes that occur in the time-since-beginning of a romantic relationship, Janina Bühler and Ulrich Orth decided to look at the time-to-separation of relationships for the purposes of their research.

With this in view, they used data from four representative studies conducted in Germany, Australia, the United Kingdom, and the Netherlands. All these countries are WEIRD, i.e., Western, Educated, Industrialized, Educated, Rich, Democratic, and their individuals are free — by law — to decide about their relationship status. For each of the four data sets covering a total of 11,295 individuals there was a control group roughly the same size consisting of couples that had not separated. The surveys in the four countries were conducted over different periods of time, ranging from 12 to 21 years. In the case of Germany, the researchers employed the data of the Panel Analysis of Intimate Relationships and Family Dynamics (pairfam), a multidisciplinary longitudinal study. In all countries, the subjects were asked to specify how satisfied they were right then with their existing romantic relationship.

Using the available data, Bühler and Orth assessed the extent to which the satisfaction with the relationship developed in the light of their subsequent separation. “In order to better understand dissolving relationships, we examined them from the point of view of time-to-separation. To do this, we applied a concept that is in general use in other fields of psychology,” said Janina Bühler. Based on the data of the four national representative studies, the researchers were able to determine that relationships can be subjected to what is known as terminal decline. This decline in relationship satisfaction occurs in two phases. The initial preterminal phase, which can have a duration of several years, is characterized by a minor decline in satisfaction. However, this is followed by a transition or tipping point from which there is an accelerated decline in satisfaction. The terminal phase of a relationship after this transition point lasts 7 to 28 months, one to two years on average. “Once this terminal phase is reached, the relationship is doomed to come to an end. This is apparent from the fact that only the individuals in the separation group go through this terminal phase, not the control group,” explained Bühler.

Partners assess the terminal phase of a relationship differently

At the same time, the two partners do not experience the transition phase in the same way. The partner who initiates the separation has already become dissatisfied with the relationship at an earlier point in time. For the recipient of the separation, the transition point arrives relatively shortly before the actual separation. They experience a very rapid decline in relationship satisfaction.

“Partners pass through various phases. They do not normally separate from one day to the next, and the way these phases impact on the two partners differs,” added Bühler. In many cases, couples seek help too late, i.e., when the transition point has already been reached. “It is thus important to be aware of these relationship patterns. Initiating measures in the preterminal phase of a relationship, i.e., before it begins to go rapidly downhill, may thus be more effective and even contribute to preserving the relationship,” concluded Bühler, who also works as a couples therapist.

Increased public concern about household products’ impact on the environment has spurred interest in replacing traditional cleaners containing ingredients such as alkylphenol polyethoxylates and phosphates with natural alternatives. Efforts to date have produced mixed results because these cleaners are difficult to make and hard to rinse off, resulting in high manufacturing and retail costs, as well as potential damage to surfaces and fabrics. Therefore, there is a desire for low-cost, easily produced, effective alternatives that are gentle on the environment and the items they are designed to clean. To address this need, Pengtao Liu and colleagues developed an eco-friendly detergent from ingredients found in abundant renewable sources.

The researchers combined cellulose nanofibers from wood with zein protein from corn to create an emulsion. Cellulose can attract and repel water, so it is effective at forming such emulsions and attracting different types of stains. The zein protein, on the other hand, helps stabilize the emulsion and trap oils. Liu and colleagues then tested the cleaning capacity of the cellulose/zein detergent on cotton fabrics and dishes stained with ink, chili oil and tomato paste. They compared the performance of their new detergent to laundry powder and commercial dish soap solutions with deionized water.

The cellulose/zein detergent was slightly less effective at cleaning the cotton cloth compared to a laundry powder solution of equal dilution (1% detergent or powder by weight). At a 5% concentration, however, the researchers’ product was more effective than the 1% laundry powder solution at cleaning each of the stains from the fabric. Microscopic examination showed that the cellulose/zein detergent left no residue on cotton fabric after washing and rinsing, which suggests it would not damage the cloth.

The researchers also tested their detergent’s capacity to remove chili oil stains from plates made of ceramic, stainless steel, glass and plastic. Again, the cellulose/zein detergent cleaned almost as well as the commercial dish soap of equal dilution, and at a 5% concentration, their product was superior. On the stainless-steel plates, for example, a 5% solution of cellulose/zein removed 92% of the stain compared to 87% with a 1% solution of commercial dish soap.

The researchers suggested that these results show that their natural detergent could be an efficient, cost-effective and sustainable alternative to synthetic cleaning agents currently on the market.

The authors acknowledge funding from the National Key Research and Development Program of China.

Researchers from Osaka Metropolitan University have discovered the ideal genetic “recipe” to turn yeast into a tiny yet powerful eco-friendly factory that converts methanol into D-lactic acid, a key compound used in biodegradable plastics and pharmaceuticals. This approach could help reduce reliance on petroleum-based processes and contribute to more sustainable chemical production.

Lactic acid is widely used in food, cosmetics, pharmaceuticals and bioplastics. It exists in two forms: L-lactic acid and D-lactic acid. Compared to its counterpart, D-lactic acid is much less available and much more expensive.

“Most lactic acid bacteria can only produce L-lactic acid whilst chemical synthesis methods yield only a mixture of both forms,” said Ryosuke Yamada, an associate professor at Osaka Metropolitan University’s Graduate School of Engineering and lead author of this study.

Seeking a more efficient way to produce D-lactic acid, the team turned to Komagataella phaffii, a yeast capable of utilizing methanol. Their goal was to pinpoint the optimal combination of D-lactate dehydrogenase (D-LDH) genes and promoters in K. phaffii that would maximize the yeast’s ability to produce D-lactic acid from methanol. D-LDH is a key enzyme responsible for converting precursor molecules into D-lactic acid, while promoters are DNA sequences that regulate gene expression.

After testing five different D-LDH genes and eight promoters, the researchers identified an ideal mix that boosted D-lactic acid production by 1.5 times compared to other methanol-based methods.

“To the best of our knowledge, our engineered yeast achieved the highest-ever reported yield using methanol as the sole carbon source,” Yamada said.

These findings show that engineered yeast strains can be tailored to produce a wide range of useful compounds for commercial use. With growing global concerns over fossil fuel depletion and environmental impact, the ability to synthesize chemicals from renewable carbon sources like methanol is deemed a critical advancement for sustainability.

“This study demonstrates that by carefully optimizing gene and promoter combinations, we can significantly enhance the efficiency of microbial processes, offering a viable alternative to traditional, petroleum-based chemical production,” Yamada said.

The study was published in Biotechnology for Biofuels and Bioproducts.

The research, led by Murdoch Children’s Research Institute (MCRI) and published in the Journal of Pediatric Surgery, found more than 40 per cent who received care in the home following a complex appendectomy recovered faster and had fewer complications.

More than 300 patients present with appendicitis to The Royal Children’s Hospital (RCH) every year, with about one in three experiencing a burst appendix or severe infection.

The study involved 83 children, aged five to 18 years, admitted to the RCH for a complicated appendicectomy, with 35 suitable for the Hospital in the Home (HITH) program. All patients needed at least five days of intravenous antibiotics (IV) post-surgery. Under the program, a nurse visited the child’s home daily to administer the antibiotics and record clinical observations.

MCRI Associate Professor Penelope Bryant said under this model, patients at home recovered more quickly and didn’t require readmission to hospital.

“Acute post-operative care at home is rare, but we found it’s possible for children to spend 35 per cent less time in hospital after complicated surgery,” she said. This could be done safely and without prolonging IV courses or broadening antibiotic use.

“These findings will help clinicians to identify which children are suitable for HITH care following surgery for complicated appendicitis.”

MCRI Associate Professor Warwick Teague said the HITH program, used heavily during the COVID-19 pandemic, had the added benefits of reduced hospital and family costs, improved quality of life, less time taken from work and prevention of hospital-acquired infections.

“The pandemic presented us with the need and opportunity to deliver care to children in their home,” he said. This study showed even children who had severe appendicitis can be well cared for at home after surgery, freeing up hospital beds for other sick children and those needing surgery.

“Traditionally after surgery for severe appendicitis, surgeons have insisted on daily reviews in hospital by the surgical team. However, in this study we learnt that optimal postoperative care be delivered at home, by well-trained non-surgical clinicians working as a team with surgeons.”

“For complicated appendicitis, the HITH program also saved over $1,400 per day for the hospital and $300 daily for families, reducing cost-of-living pressures with longer-term benefits for healthcare sustainability.”

Researchers from The Royal Children’s Hospital and University of Melbourne contributed to the study.

Joint senior author Associate Professor Nic Rawlence, Director of the Otago Palaeogenetics Laboratory, says while elephant seals now only inhabit the subantarctic islands and South America, Aotearoa beaches used to be “heaving” with the colossal animals.

“At the time of human arrival in New Zealand, you would be hard pressed to find room on the beaches, with fur seals on the rocky headlands, prehistoric sealions and elephant seals on the sand, and lots of penguins,” he says.

“It’s a picture that is very hard to imagine today, especially as most New Zealanders wouldn’t think that these majestic giants were once part of our biological heritage.”

The study was undertaken by a group of international researchers, led by postgraduate students Andrew Berg, of the University of Sydney, and Otago’s Megan Askew, and recently published in the leading journal Global Change Biology.

They used palaeogenetic techniques on specimens dating back thousands of years from New Zealand, Tasmania and Antarctica to show that southern elephant seals used to be spread across the entire Southern Ocean.

Joint senior author Dr Mark de Bruyn, of Griffith University, says their whereabouts was heavily impacted by climate change and humans over a short evolutionary period.

“The Ice Ages would have rapidly increased the amount of sea ice surrounding Antarctica, forcing elephant seals to retreat to multiple refugia in South Africa, Australia, New Zealand and South America, before they expanded back out as the climate warmed, including temporarily to the Antarctic mainland,” Dr de Bruyn says.

“However, indigenous subsistence hunting and European industrial sealing once again resulted in the contraction of their range, this time to the deep Southern Ocean with their extirpation from Australia and New Zealand.”

Associate Professor Rawlence says knowing how elephant seals responded to these changes will provide insights into how they — and the Southern Ocean ecosystem, which New Zealand and Australia are part of — may be impacted in the future.

“Their dynamic evolutionary history, plus climate change and human impact, strongly suggests that unless measures are taken to mitigate the effects of human-driven climate change and marine ecosystem deterioration, elephant seals and the Southern Ocean ecosystem are in for a rough ride into the future,” he says.