Publisher Health

A New York-based, multi-institutional research team has found high levels of three toxic metabolites produced by gut bacteria in the cerebrospinal fluid and plasma samples of multiple sclerosis (MS) patients. The important findings, published in the journal Brain, further scientists’ understanding of how gut bacteria can impact the course of neurological diseases by producing compounds that are toxic to nerve cells.
Previously published evidence has supported the concept that an imbalance in the gut microbiota — the community of organisms that live in the human intestines — may underly a range of neurological disorders. Researchers also found that certain gut bacteria are either enriched or depleted in MS patients compared to healthy individuals, but it is unclear how these microbes communicate with the brain and affect the neurodegenerative disease process.
“Our findings suggest that MS patients’ gut bacteria produce and release large amounts p-cresol-sulfate, indoxyl-sulfate and N-phenylacetylglutamine into the bloodstream, and they eventually reach the cerebrospinal fluid,” said Hye-Jin Park, one of the lead authors on the study and a research associate with the Neuroscience Initiative at the Advanced Science Research Center at the Graduate Center, CUNY (CUNY ASRC) “Once there, these toxic metabolites bathe the brain and spinal cord, and potentially play a role in the destruction of the myelin sheath that protect nerves.”
For the study, the research team obtained blood and cerebrospinal fluid samples from volunteer patients at the Multiple Sclerosis Center of Northeastern New York. Samples were taken from patients before and after treatment with the disease modifying therapy dimethyl fumarate (DMF), which has been reported to have a profound effect on reshaping the gut microbiome of MS patients. The analyzed data allowed researchers to identify an abundance of the three toxic metabolites in MS patients not treated with DMF compared to healthy individuals. They also noted a reduction in the metabolites following treatment with DMF.
“The presence of high levels of these toxic metabolites also correlates with biomarkers of neurodegeneration in MS patients, and with the ability to impair neuronal function of cultured cells in the laboratory,” said Achilles Ntranos, a lead author of the study and assistant professor of Neurology at the Icahn School of Medicine at Mount Sinai, where a second set of samples was collected from MS patients.
“This is an exciting and significant discovery,” said Patrizia Casaccia, the study’s primary investigator and the founding director of the CUNY ASRC’s Neuroscience Initiative. “This work not only furthers our understanding of the role of gut-brain communication in neurodegenerative disease progression, but also provides a potential metabolic target for develop new MS Therapies.”
The research team included scientists from the CUNY ASRC, MS Center of Northeastern New York, Icahn School of Medicine at Mount Sinai and BERG Health. The study was supported with funding from Biogen.
Story Source:
Materials provided by Advanced Science Research Center, GC/CUNY. Note: Content may be edited for style and length.

The head of the World Health Organization has warned that events might need to be cancelled, with the Covid-19 Omicron variant continuing to spread and families and friends planning to meet up over the festive period.Speaking in Geneva, Dr Tedros Adhanom Ghebreyesus said: “It’s better to cancel now and celebrate later, than to celebrate now and grieve later.”

A group of Alzheimer’s experts and health advocates called on the F.D.A. to withdraw its approval of the drug, the latest of several setbacks for the treatment.Biogen slashed the price of its controversial new Alzheimer’s drug Aduhelm on Monday as the drug faces weak sales and mounting criticism.The price was reduced to $28,200 a year from $56,000 on the same day that a group of Alzheimer’s experts and health advocates called on the Food and Drug Administration to pull the drug off the market and said they were supporting an effort to file a formal petition with the agency to withdraw it.“The F.D.A.’s decision to approve Aduhelm is indefensible in both scientific and clinical terms,” said a statement signed by 18 scientists, most of them doctors. “This drug should be withdrawn from the market immediately.”The agency approved Aduhelm in June, even though a council of senior F.D.A. officials, an advisory committee of outside experts and many Alzheimer’s specialists said the scientific evidence showed that the drug did not provide a clear benefit to patients and that it carried risks of dangerous side effects.Major health systems, including Cleveland Clinic, Mount Sinai Health System, Mass General Brigham and the Department of Veterans Affairs have declined to offer Aduhelm, citing questions about its benefits and risks. In October, Biogen reported that Aduhelm had brought in just $1.9 million in revenue through September, a strikingly small amount given that about 1.5 million Americans have the mild Alzheimer’s-related dementia that makes them eligible for the drug.In a statement about the price-cutting on Monday, Michel Vounatsos, Biogen’s chief executive officer, said the company had “listened to the feedback of our stakeholders” and believed that “too many patients are not being offered the choice of Aduhelm due to financial considerations.”But Brian Skorney, an analyst at Robert W. Baird & Company, said after the price announcement: “For the broad majority of people who are critical of Aduhelm, $56,000 and $28,000 are both exceptionally high prices for a drug that a lot of people perceive doesn’t work at all.”The statement from Alzheimer’s experts and health advocates calling on the F.D.A. to withdraw Aduhelm grew out of a three-hour video meeting among the scientists last week.“We’re not just saying the approval was probably the worst decision the F.D.A. ever made,” Dr. Peter Whitehouse, a neurologist and Alzheimer’s expert at Case Western Reserve University who led the Dec. 15 meeting, told attendees during the session. “It’s so bad that we should advocate for withdrawal.”The doctors and scientists who signed the statement also agreed to provide their expertise to support the filing of a citizen petition, a formal process to seek reversal of the F.D.A.’s decision. The petition will be filed by the Right Care Alliance, a coalition of clinicians, patients and community members, which is also circulating a pledge for physicians who promise not to prescribe Aduhelm and for patients and family members who say they will not request it.Dr. Vikas Saini, chairman of the Right Care Alliance and president of the Lown Institute, a health care think tank, said that while the citizen petition process can take months or years, it can prompt F.D.A. action.Dr. Saini, who helped organize last week’s meeting, said that out of 45 citizen petitions filed since 1971 by the group Public Citizen, in 27 cases the F.D.A. withdrew drugs from the market and in seven other cases the agency sharply restricted a drug’s use.In response to the call to withdraw approval of Aduhelm, also known by its scientific name, aducanumab, an F.D.A. spokeswoman said that “the data set for Aduhelm was very complex, and our review has been thorough.”The spokeswoman also said that “careful analyses of the Phase 2 and Phase 3 clinical trials support the conclusion that it is likely that Aduhelm provides clinical benefit — although the data currently available do not provide substantial evidence of effectiveness on clinical benefit.”Aduhelm has also been encountering resistance in other countries. On Friday, reviewers at the European Union’s drug regulator, the European Medicines Agency, recommended against approving Aduhelm, a decision that Biogen said it would ask to be re-examined.Aduhelm is a monoclonal antibody, given as a monthly infusion. In clinical trials, 41 percent of patients receiving the F.D.A.-approved higher dose experienced brain swelling or brain bleeding, often mild, but serious in some cases.Pool photo by Jessica RinaldiSeveral months ago, leading Canadian Alzheimer’s research organizations said that approving the drug in Canada “cannot be justified.”Dr. Howard Chertkow, scientific director of the Canadian Consortium on Neurodegeneration in Aging, was one of three Alzheimer’s experts from outside the United States who signed the statement calling on the F.D.A. to withdraw the drug. “We feel it’s an abrogation of our responsibility as physicians to allow a marginal medication with a very high cost associated with it to come into the country, so we’re quite active in trying to block what has happened in the states from occurring in Canada,” he said at last week’s meeting.Two nearly identical clinical trials of Aduhelm, a monoclonal antibody given as a monthly infusion, were stopped early because an independent data monitoring committee concluded that the drug didn’t appear to be beneficial. A later analysis by Biogen found that participants receiving the high dose of the drug in one trial had experienced a very slight slowing of cognitive decline but that participants in the other trial had not benefited at all.About 41 percent of patients receiving the high dose — the dose the F.D.A. approved — experienced brain swelling or brain bleeding, side effects that were often mild or asymptomatic, but were sometimes serious.Monday’s statement also objects to the F.D.A.’s justification for its approval. Acknowledging there was insufficient evidence that Aduhelm would help patients, the agency greenlighted it under a program called “accelerated approval,” which allows authorization of drugs without proof of benefit for serious diseases that have few treatment options if the drug affects part of the disease’s biology (known as a surrogate endpoint) in a way that is “reasonably likely to predict clinical benefit.”The F.D.A. based its approval on Aduhelm’s ability to reduce a protein called amyloid that forms plaques in the brains of people with Alzheimer’s. But experts say years of studies have not shown that reducing amyloid helps memory or thinking problems.Approving the drug because of amyloid reduction “will have huge and wide-ranging negative implications for patients, families” and dementia research, Dr. Kenneth Langa, a professor of medicine at the University of Michigan, said in last week’s meeting. The group’s statement, which includes a section for others to sign their names in support, plays on the F.D.A.’s language by calling for “accelerated withdrawal.”“Reading the justification of the F.D.A. was like watching a ‘Saturday Night Live’ skit for data nerds.” Dr. Saini said. “I mean, I had trouble believing it.”The agency’s approval requires that Biogen conduct another trial to see if Aduhelm works. In its response Monday, the F.D.A. spokeswoman said “we believe that the data support accelerated approval while holding the company accountable for conducting an additional study.” Last week, Biogen said that it had developed a protocol to get that trial completed in 2026, several years before the F.D.A.-imposed deadline.Before he signed Monday’s statement, Dr. Sam Gandy, director of Mount Sinai’s Center for Cognitive Health, who helped organize the meeting, said that with advocacy groups like the Alzheimer’s Association still supporting the drug’s approval, he had a “concern that calling for something may trigger a backlash that undoes where we really want to go.”But Dr. Jerry Avorn, a professor of medicine at Harvard Medical School who also signed the statement, said that while it was unlikely that calling for withdrawal would make F.D.A. officials say, “‘Yeah, they’re right, we goofed, we better undo this decision,’” the action was nonetheless important. “We’re taking a stand and saying the process was terrible and the outcome was terrible, and even if they don’t listen to it, it’ll be kind of a shot across the bow.”Rebecca Robbins contributed reporting.

The vaccine will be the fifth to become available in the E.U., which already has ample supplies.The European Commission on Monday authorized a Covid-19 vaccine made by Novavax, making it the fifth vaccine available in the 27 nations of the European Union.“At a time where the Omicron variant is rapidly spreading, and where we need to step up vaccination and the administration of boosters, I am particularly pleased with today’s authorization of the Novavax vaccine,” Ursula von der Leyen, president of the European Commission, said in a statement.But it’s not yet clear how well the vaccine, known as Nuvaxovid, will work against the contagious new Omicron variant. And there may not be much demand for the new vaccine in Europe, which is already flush with vaccines from Pfizer-BioNTech and other sources.Novavax, based in Maryland, last year won $1.7 billion in support from the United States government to develop a vaccine made of proteins from the coronavirus. Despite the lavish support, Novavax lagged behind the vaccine developers Pfizer-BioNTech and Moderna, and struggled with its clinical trials and manufacturing.Eventually, however, Novavax demonstrated that its vaccine could offer strong protection. In a final report published last week in The New England Journal of Medicine, company researchers found that Nuvaxovid was 90 percent effective against symptomatic infection and 100 percent effective against moderate to severe disease.Protein-based vaccines have been used for decades and generally have a strong track record of safety and mild side effects. Nuvaxovid’s side effects are usually mild or moderate and clear up within a couple days.Novavax teamed up with the Serum Institute of India as a manufacturing partner, and in recent weeks the new vaccine had a string of regulatory successes. Indonesia and the Philippines authorized the vaccine last month.The World Health Organization last week granted Nuvaxovid an emergency-use listing, a seal of approval that accelerates the adoption of vaccines in countries that cannot conduct large-scale reviews of their own.Already, Novavax has lined up a number of purchase orders. The company also plans to supply 1.1 billion doses to Covax, a consortium that seeks to distribute vaccines to countries around the world. In a Nov. 4 earnings call, Novavax officials said that they anticipated producing over two billion doses in 2022.In August, the European Commission agreed to purchase up to 200 million doses of the vaccine. The commission authorized Nuvaxovid after a recommendation issued on Monday by the European Medicines Agency.In a statement, Novavax said that it expected initial doses to arrive in Europe in January.But Europe has been using other vaccines for nearly a year, and the European Commission has locked up an abundant supply, with an agreement for up to 2.4 billion doses from Pfizer-BioNTech alone.On Monday, Pfizer-BioNTech announced that an agreement was reached with the European Commission to purchase over 200 million doses in 2022. Those would be in addition to the 450 million doses already set to be delivered in 2022.The Coronavirus Pandemic: Key Things to KnowCard 1 of 5The Omicron variant.

A researcher at the University of Houston College of Pharmacy has identified the proteins necessary for efficient regeneration of skeletal muscles after acute injury and in Duchenne Muscular Dystrophy (DMD). Ashok Kumar, Else and Philip Hargrove Endowed Professor of Pharmacological and Pharmaceutical Sciences, is reporting his findings in eLife.
Skeletal muscles, which connect your bones and allow you to move, contain 50-75% of all the body’s proteins. Not only are they the most abundant and dynamic tissue of the human body essential for posture, locomotion and breathing, but they also control the body’s entire metabolism.
So, when skeletal muscles get hurt or injured either through trauma or degenerative disease, it can become complicated.
“We identified that the IRE1 protein — localized on the membrane of endoplasmic reticulum (the organelle that is involved in the production, folding and quality control of proteins) and XBP1 protein are important for efficient regeneration of skeletal muscle after injury and in DMD,” reports Kumar. Anirban Roy, research assistant professor of pharmacology, is the paper’s first author.
Understanding the mechanisms of skeletal muscle regeneration is essential for the development of new therapeutics aimed at treating various genetic and acquired degenerative muscle disorders.
“We found that skeletal muscle repair was considerably diminished in models in which IRE1 or XBP1 protein was specifically removed from skeletal muscle. These proteins support skeletal muscle regeneration through enhancing the proliferation of resident muscle stem cells. Deletion of IRE1 in skeletal muscle reduces abundance of muscle stem cells and exaggerates muscular dystrophy phenotype,” said Kumar.
Ongoing studies in the Kumar laboratory are investigating whether recently developed highly specific pharmacological activators of IRE1 and XBP1 can improve skeletal muscle regeneration after acute injury and other muscle degenerative diseases.
“The research work has enormous scope for drug development for skeletal muscle diseases,” said Kumar.
Story Source:
Materials provided by University of Houston. Original written by Laurie Fickman. Note: Content may be edited for style and length.

Human anatomy still has a few surprises in store for us: researchers at the University of Basel have discovered a previously overlooked section of our jaw muscles and described this layer in detail for the first time.
The masseter muscle is the most prominent of the jaw muscles. If you place your fingers on the back of your cheeks and press your teeth together, you’ll feel the muscle tighten. Anatomy textbooks generally describe the masseter as consisting of one superficial and one deep part.
Now, researchers led by Dr. Szilvia Mezey from the Department of Biomedicine at the University of Basel and Professor Jens Christoph Türp from the University Center for Dental Medicine Basel (UZB) have described the structure of the masseter muscle as consisting of an additional third, even deeper layer. In the scientific journal Annals of Anatomy, they propose that this layer be given the name Musculus masseter pars coronidea — in other words, the coronoid section of the masseter — because the newly described layer of muscle is attached to the muscular (or “coronoid”) process of the lower jaw.
The anatomical study was based on detailed examination of formalin-fixed jaw musculature, computer tomographic scans and the analysis of stained tissue sections from deceased individuals who had donated their bodies to science. This was in addition to MRI data from a living person.
As if a new animal species had been discovered
“This deep section of the masseter muscle is clearly distinguishable from the two other layers in terms of its course and function,” explains Mezey. The arrangement of the muscle fibers, she says, suggests that this layer is involved in the stabilization of the lower jaw. It also appears to be the only part of the masseter that can pull the lower jaw backwards — that is, toward the ear.
A look at historical anatomy studies and textbooks reveals that the structure of the masseter muscle has already raised questions in the past. In a previous edition of Gray’s Anatomy, from the year 1995, the editors also describe the masseter muscle as having three layers, although the cited studies were based on the jaw musculature of other species and partly contradicted one another.
Other individual studies from the early 2000s also reported three layers, but they divided the superficial section of the masseter into two layers and agreed with standard works in their description of the deeper section.
“In view of these contradictory descriptions, we wanted to examine the structure of the masseter muscle again comprehensively,” says Türp. “Although it’s generally assumed that anatomical research in the last 100 years has left no stone unturned, our finding is a bit like zoologists discovering a new species of vertebrate.”
Story Source:
Materials provided by University of Basel. Note: Content may be edited for style and length.

Intensive lifestyle intervention with plenty of exercise helps people with prediabetes improve their blood glucose levels over a period of years and thus delay or even prevent type 2 diabetes. In particular, individuals with prediabetes at highest risk benefited from intensive lifestyle intervention. This is shown by the evaluation of the Prediabetes Lifestyle Intervention Study (PLIS) of the German Center for Diabetes Research (DZD), which was conducted at 8 sites of the center throughout Germany. The results have now been published in the journal Diabetes.
More exercise and healthy eating behavior help many people with prediabetes to normalize their blood glucose levels and avoid developing type 2 diabetes. However, not everyone benefits from a conventional lifestyle intervention (LI). Recent studies show that already in prediabetes, there are different subtypes with different risk profiles. Researchers at the German Center for Diabetes Research (DZD) have therefore investigated in a multicenter randomized controlled trial whether people with prediabetes and a high risk benefit from an intensification of the intervention and how people with a low risk are affected by a conventional LI compared to no lifestyle changes.
The LI lasted 12 months in each case and the follow-up period was a further two years. A total of 1,105 individuals with prediabetes were investigated at various study sites in Germany and assigned to a high-risk or low-risk phenotype based on insulin secretion, insulin sensitivity, and liver fat content. 82% of participants completed the study.
A lot helps a lot — more exercise improves blood glucose and cardiometabolic values
People at high risk — these individuals produce too little insulin or suffer from fatty liver with insulin resistance — were randomly assigned to receive conventional LI according to the Diabetes Prevention Program (DPP) or a more intensive intervention with double the amount of required exercise. The results showed that more exercise, i.e. more intensive LI, helps people at high risk improve their blood glucose and cardiometabolic levels and reduce liver fat content to within the normal range. Conventional LI is less effective.
Low-risk participants completed a conventional LI or took part in a control group that received only a one-time brief consultation. “After three years, glucose tolerance was more likely to normalize in participants with conventional LI than in those in the control group,” said Professor Hans-Ulrich Häring of the German Center for Diabetes Research and last author of the study. There were hardly any differences in insulin sensitivity and secretion, liver fat content and cardiometabolic risk.
Lifestyle intervention based on risk phenotype improves diabetes prevention
“Our study results show that an individualized LI based on the risk phenotype is beneficial for diabetes prevention,” said study leader Professor Andreas Fritsche from the Institute of Diabetes Research and Metabolic Diseases of Helmholtz Munich at the University of Tübingen (IDM) and the Department of Diabetology, Endocrinology and Nephrology (Director: Professor Andreas Birkenfeld, MD) at Tübingen University Hospital, summarizing the results. “For successful prevention, we need to identify high-risk patients in the future and focus on providing them with an intensified lifestyle intervention.”
Story Source:
Materials provided by Deutsches Zentrum fuer Diabetesforschung DZD. Note: Content may be edited for style and length.

Exercise not only trains the muscles but can also prevent the development of fatty liver. A new study by the German Center for Diabetes Research (DZD), Helmholtz Munich and Tübingen University Hospital shows which molecular adaptations, in particular of the liver mitochondria, can be observed in this process. The study has now been published in Molecular Metabolism.
Worldwide one in four persons suffers from non-alcoholic liver disease (NAFLD, also called metabolic liver disease MAFLD). Those affected often have type 2 diabetes as well as an increased risk of liver cirrhosis and cardiovascular diseases. In addition, NAFLD is associated with increased mortality. An imbalance between energy intake and consumption is discussed as a cause for the disease. This leads to fat deposits in the liver and over time impairs the function of the mitochondria * — both risk factors for the development of hepatic insulin resistance and liver inflammation.
How exercise modifies the adaptation of the liver to increased energy intake
To prevent and treat NAFLD, lifestyle modification with increased physical activity is recommended. To what extent regular exercise alters the adaptation of the liver to increased energy intake and what role skeletal muscle plays in this process was investigated by scientists at the Institute of Clinical Chemistry and Pathobiochemistry at Tübingen University Hospital and at the Institute of Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen. The researchers collaborated with the Institute of Experimental Genetics (IEG) at Helmholtz Munich, the Leibniz Institute for Analytical Sciences in Dortmund, and the Dalian Institute of Chemical Physics in China.
Exercise can prevent fatty liver disease caused by overnutrition
In the study conducted by Dr. Miriam Hoene and Dr. Lisa Kappler, mice were fed a high-energy diet. Some of the mice also received regular treadmill training. Following the six-week intervention, the researchers examined the animals’ livers and muscles for changes in the transcriptome, the mitochondrial proteome, lipid composition, and the mitochondrial function.
The results showed that training regulated important enzymes of glucose and fructose degradation in the liver as well as the mitochondrial pyruvate metabolism. In this way, the substrate burden for mitochondrial respiration and lipid synthesis can be reduced. As a consequence, less fat is stored in the liver — and specific lipids such as diacylglycerol species are lowered. Moreover, glucose control improves in the exercise trained mice. In addition, an increased respiratory capacity of the skeletal muscles relieves the metabolic stress in the liver.
The systems biology data offer a comprehensive insight into the molecular adaptation of the liver and muscles to a high-energy diet, training, and combinatorial effects. “The results fit in very well with the approaches of ongoing clinical studies in which inhibitors are tested against some of the targets found here, such as the mitochondrial pyruvate transporter,” said DZD scientist Prof. Dr. Cora Weigert, head of the study and professor of molecular diabetology at Tübingen University Hospital. “They also show that regular physical activity regulates many targets at the same time key nodes of metabolic pathways, an effect that cannot be achieved with monotherapy.”
*Mitochondria
The task of the mitochondria is to make energy available to the cell, which occurs through cellular respiration. This is a metabolic process in which energy stored in glucose and other organic substances is obtained by breaking the chemical bond, ultimately yielding adenosine triphosphate, or ATP. This is the most important energy molecule in the body. Mitochondria are therefore also considered the power plants of the cell.
Story Source:
Materials provided by Deutsches Zentrum fuer Diabetesforschung DZD. Note: Content may be edited for style and length.

Anthrax has a scary reputation. Widely known to cause serious lung infections in humans and unsightly, albeit painless, skin lesions in livestock and people, the anthrax bacterium has even been used as a weapon of terror.
Now the findings of a new study suggest the dreaded microbe also has unexpected beneficial potential — one of its toxins can silence multiple types of pain in animals.
The research reveals that this specific anthrax toxin works to alter signaling in pain-sensing neurons and, when delivered in a targeted manner into neurons of the central and peripheral nervous system, can offer relief to animals in distress.
The work, led by investigators at Harvard Medical School in collaboration with industry scientists and researchers from other institutions, is published Dec. 20 in Nature Neuroscience.
Furthermore, the team combined parts of the anthrax toxin with different types of molecular cargo and delivered it into pain-sensing neurons. The technique can be used to design novel precision-targeted pain treatments that act on pain receptors but without the widespread systemic effects of current pain-relief drugs, such as opioids.
“This molecular platform of using a bacterial toxin to deliver substances into neurons and modulate their function represents a new way to target pain-mediating neurons,” said study senior investigator Isaac Chiu, associate professor of immunology in the Blavatnik Institute at Harvard Medical School.

New research has moved a step closer to harnessing viruses to fight bacterial infection, reducing the threat of antibiotic resistance.
A growing number of infections, including pneumonia, tuberculosis, gonorrhoea, and salmonellosis, are developing antibiotic resistance, which means they becoming harder to treat, resulting in higher death rates, longer hospital stays and higher costs.
Phage therapy is the concept of using viruses (known as phage) that are harmless to humans to kill bacteria. Phage therapy can be used in combination with antibiotics to cure infections more effectively, and reduce the opportunity for bacteria to develop antibiotic resistance. However, bacteria can also evolve resistance to phages.
The new study by the University of Exeter, published in Cell Host Microbe, has cast new light on how to best combine antibiotics and phage therapy. Researchers conducted laboratory experiments on Pseudomonas aeruginosa a bacterium which causes disease in immunocompromised and cystic fibrosis patients. They exposed the bacterium to eight types of antibiotics — and found differences in the mechanisms by which the bacteria evolve resistance to phages, which affect how harmful they are.
Viruses penetrate molecules on the cell surface to infect bacteria. Like the human immune system, bacteria have their own CRISPR defence system, made up of proteins that fight off infection. As in human immune responses, this means that the virus infects the bacteria, and is then killed. In the process, the bacteria’s CRISPR system learns to recognise and attack the virus in future.
However, the bacteria have a second defence option. They can also change their own cell surface to ward off infection, losing the receptor to which phages normally attach. This option comes with a cost to bacteria — the bacteria become less virulent, meaning they no longer cause disease, or the disease becomes less severe.