Neuroscience

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Leprosy Bacteria Turn Nerve System Cells into Stem Cells
The study, carried out in mice, found that in the early stages of infection, M. leprae were able to protect themselves from the body’s immune system by hiding in the Schwann cells. Once the infection was fully established, the bacteria were able to convert the Schwann cells to become like stem cells.
Like typical stem cells, these cells were pluripotent, meaning they could then become other cell types, for instance muscle cells. This enabled M. leprae to spread to tissues in the body.
The study, published in the journal Cell, also shows that the bacteria-generated stem cells have unexpected characteristic. They can secrete specialized proteins – called chemokines – that attract immune cells, which in turn pick up the bacteria and spread the infection.
“We have found a new weapon in a bacteria’s armory that enables them to spread effectively in the body by converting infected cells to stem cells. Greater understanding of how this occurs could help research to diagnose bacterial infectious diseases, such as leprosy, much earlier,” said study lead author Prof Anura Rambukkana, Medical Research Council Center for Regenerative Medicine at the University of Edinburgh.
“This is very intriguing as it is the first time that we have seen that functional adult tissue cells can be reprogrammed into stem cells by natural bacterial infection, which also does not carry the risk of creating tumorous cells. Potentially you could use the bacteria to change the flexibility of cells, turning them into stem cells and then use the standard antibiotics to kill the bacteria completely so that the cells could then be transplanted safely to tissue that has been damaged by degenerative disease.”
Dr Rob Buckle, Head of Regenerative Medicine at the Medical Research Council Center for Regenerative Medicine at the University of Edinburgh, said: “this ground-breaking new research shows that bacteria are able to sneak under the radar of the immune system by hijacking a naturally occurring mechanism to ‘reprogramme’ cells to make them look and behave like stem cells. This discovery is important not just for our understanding and treatment of bacterial disease, but for the rapidly progressing field of regenerative medicine. In future, this knowledge may help scientists to improve the safety and utility of lab-produced pluripotent stem cells and help drive the development of new regenerative therapies for a range of human diseases, which are currently impossible to treat.”
The scientists believe mechanisms used by leprosy bacteria could exist in other infectious diseases. Knowledge of this newly discovered tactic used by bacteria to spread infection could help research to improve treatments and earlier diagnosis of infectious diseases.

Leprosy Bacteria Turn Nerve System Cells into Stem Cells

The study, carried out in mice, found that in the early stages of infection, M. leprae were able to protect themselves from the body’s immune system by hiding in the Schwann cells. Once the infection was fully established, the bacteria were able to convert the Schwann cells to become like stem cells.

Like typical stem cells, these cells were pluripotent, meaning they could then become other cell types, for instance muscle cells. This enabled M. leprae to spread to tissues in the body.

The study, published in the journal Cell, also shows that the bacteria-generated stem cells have unexpected characteristic. They can secrete specialized proteins – called chemokines – that attract immune cells, which in turn pick up the bacteria and spread the infection.

“We have found a new weapon in a bacteria’s armory that enables them to spread effectively in the body by converting infected cells to stem cells. Greater understanding of how this occurs could help research to diagnose bacterial infectious diseases, such as leprosy, much earlier,” said study lead author Prof Anura Rambukkana, Medical Research Council Center for Regenerative Medicine at the University of Edinburgh.

“This is very intriguing as it is the first time that we have seen that functional adult tissue cells can be reprogrammed into stem cells by natural bacterial infection, which also does not carry the risk of creating tumorous cells. Potentially you could use the bacteria to change the flexibility of cells, turning them into stem cells and then use the standard antibiotics to kill the bacteria completely so that the cells could then be transplanted safely to tissue that has been damaged by degenerative disease.”

Dr Rob Buckle, Head of Regenerative Medicine at the Medical Research Council Center for Regenerative Medicine at the University of Edinburgh, said: “this ground-breaking new research shows that bacteria are able to sneak under the radar of the immune system by hijacking a naturally occurring mechanism to ‘reprogramme’ cells to make them look and behave like stem cells. This discovery is important not just for our understanding and treatment of bacterial disease, but for the rapidly progressing field of regenerative medicine. In future, this knowledge may help scientists to improve the safety and utility of lab-produced pluripotent stem cells and help drive the development of new regenerative therapies for a range of human diseases, which are currently impossible to treat.”

The scientists believe mechanisms used by leprosy bacteria could exist in other infectious diseases. Knowledge of this newly discovered tactic used by bacteria to spread infection could help research to improve treatments and earlier diagnosis of infectious diseases.

Filed under nerve cells stem cells immune system Schwann cells bacteria infectious diseases science

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Cheap and easy technique to snip DNA could revolutionize gene therapy
A simple, precise and inexpensive method for cutting DNA to insert genes into human cells could transform genetic medicine, making routine what now are expensive, complicated and rare procedures for replacing defective genes in order to fix genetic disease or even cure AIDS.
Discovered last year by Jennifer Doudna and Martin Jinek of the Howard Hughes Medical Institute and University of California, Berkeley, and Emmanuelle Charpentier of the Laboratory for Molecular Infection Medicine-Sweden, the technique was labeled a “tour de force” in a 2012 review in the journal Nature Biotechnology.
That review was based solely on the team’s June 28, 2012, Science paper, in which the researchers described a new method of precisely targeting and cutting DNA in bacteria.
Two new papers published last week in the journal Science Express (1 , 2) demonstrate that the technique also works in human cells. A paper by Doudna and her team reporting similarly successful results in human cells has been accepted for publication by the new open-access journal eLife.
“The ability to modify specific elements of an organism’s genes has been essential to advance our understanding of biology, including human health,” said Doudna, a professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute Investigator at UC Berkeley. “However, the techniques for making these modifications in animals and humans have been a huge bottleneck in both research and the development of human therapeutics.
“This is going to remove a major bottleneck in the field, because it means that essentially anybody can use this kind of genome editing or reprogramming to introduce genetic changes into mammalian or, quite likely, other eukaryotic systems.”
“I think this is going to be a real hit,” said George Church, professor of genetics at Harvard Medical School and principal author of one of the Science Express papers. “There are going to be a lot of people practicing this method because it is easier and about 100 times more compact than other techniques.”
“Based on the feedback we’ve received, it’s possible that this technique will completely revolutionize genome engineering in animals and plants,” said Doudna, who also holds an appointment at Lawrence Berkeley National Laboratory. “It’s easy to program and could potentially be as powerful as the Polymerase Chain Reaction (PCR).”
The latter technique made it easy to generate millions of copies of small pieces of DNA and permanently altered biological research and medical genetics.

Cheap and easy technique to snip DNA could revolutionize gene therapy

A simple, precise and inexpensive method for cutting DNA to insert genes into human cells could transform genetic medicine, making routine what now are expensive, complicated and rare procedures for replacing defective genes in order to fix genetic disease or even cure AIDS.

Discovered last year by Jennifer Doudna and Martin Jinek of the Howard Hughes Medical Institute and University of California, Berkeley, and Emmanuelle Charpentier of the Laboratory for Molecular Infection Medicine-Sweden, the technique was labeled a “tour de force” in a 2012 review in the journal Nature Biotechnology.

That review was based solely on the team’s June 28, 2012, Science paper, in which the researchers described a new method of precisely targeting and cutting DNA in bacteria.

Two new papers published last week in the journal Science Express (1 , 2) demonstrate that the technique also works in human cells. A paper by Doudna and her team reporting similarly successful results in human cells has been accepted for publication by the new open-access journal eLife.

“The ability to modify specific elements of an organism’s genes has been essential to advance our understanding of biology, including human health,” said Doudna, a professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute Investigator at UC Berkeley. “However, the techniques for making these modifications in animals and humans have been a huge bottleneck in both research and the development of human therapeutics.

“This is going to remove a major bottleneck in the field, because it means that essentially anybody can use this kind of genome editing or reprogramming to introduce genetic changes into mammalian or, quite likely, other eukaryotic systems.”

“I think this is going to be a real hit,” said George Church, professor of genetics at Harvard Medical School and principal author of one of the Science Express papers. “There are going to be a lot of people practicing this method because it is easier and about 100 times more compact than other techniques.”

“Based on the feedback we’ve received, it’s possible that this technique will completely revolutionize genome engineering in animals and plants,” said Doudna, who also holds an appointment at Lawrence Berkeley National Laboratory. “It’s easy to program and could potentially be as powerful as the Polymerase Chain Reaction (PCR).”

The latter technique made it easy to generate millions of copies of small pieces of DNA and permanently altered biological research and medical genetics.

Filed under Cas9 gene therapy DNA DNA cleavage bacteria genetics genome science

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How the animals lost their sensors
For free-living organisms, the ability to sense and respond to the outside environment is crucial for survival. Eukaryotes, such as animals and plants, often have highly complex network systems in place to monitor their surroundings and respond effectively, but bacteria have developed a remarkably simple system. It’s called the ‘Two Component System’ because it literally relies on just two components; a sensor and a responder. The sensor picks up the signal, communicates this to the responder, which then causes the effect.
The picture above shows this process happening. The ‘communication’ of the message from the sensor to the responder, as shown by the coloured arrows, is carried out by transferring phosphate molecules. The signal interacting with the sensor causes the sensor to autophosphorylate (phosphorylate itself) and then pass the phosphate molecule onto the responder to trigger the response. The letters “H” and “D” are the actual amino-acids being phosphorylated; Histadine and Aspartate.
Although Two-Component Systems (TCS) are found in all three superkingdoms of life (archaea, bacteria and eukaryotes) they are suspiciously absent from the animal kingdom. Plants have them, as do fungi and several protazoa, but they just aren’t present in animals. For this reason they’ve been looked into as potential antibiotic targets as knocking out the Two-Component Systems of most bacteria is fatal.
Why don’t animals use TCS? To answer this you have to start looking at the evolution of the system itself, because despite being nominally present in eukaryotes such as plants and fungi, TCS are used very differently. Bacteria use TCS for sensing a wide variety of signals; stress, metabolism, nutrient regulation, chemotaxis, pathogen-host interactions etc. In eukaryotes on the other hand they are used sparingly; for ethylene responses and photosensitivity in plants and osmoregulation in fungi and slime moulds.

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How the animals lost their sensors

For free-living organisms, the ability to sense and respond to the outside environment is crucial for survival. Eukaryotes, such as animals and plants, often have highly complex network systems in place to monitor their surroundings and respond effectively, but bacteria have developed a remarkably simple system. It’s called the ‘Two Component System’ because it literally relies on just two components; a sensor and a responder. The sensor picks up the signal, communicates this to the responder, which then causes the effect.

The picture above shows this process happening. The ‘communication’ of the message from the sensor to the responder, as shown by the coloured arrows, is carried out by transferring phosphate molecules. The signal interacting with the sensor causes the sensor to autophosphorylate (phosphorylate itself) and then pass the phosphate molecule onto the responder to trigger the response. The letters “H” and “D” are the actual amino-acids being phosphorylated; Histadine and Aspartate.

Although Two-Component Systems (TCS) are found in all three superkingdoms of life (archaea, bacteria and eukaryotes) they are suspiciously absent from the animal kingdom. Plants have them, as do fungi and several protazoa, but they just aren’t present in animals. For this reason they’ve been looked into as potential antibiotic targets as knocking out the Two-Component Systems of most bacteria is fatal.

Why don’t animals use TCS? To answer this you have to start looking at the evolution of the system itself, because despite being nominally present in eukaryotes such as plants and fungi, TCS are used very differently. Bacteria use TCS for sensing a wide variety of signals; stress, metabolism, nutrient regulation, chemotaxis, pathogen-host interactions etc. In eukaryotes on the other hand they are used sparingly; for ethylene responses and photosensitivity in plants and osmoregulation in fungi and slime moulds.

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Filed under animals bacteria evolution proteins Two Component System science

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How bacteria talk to each other and our cells
Bacteria can talk to each other via molecules they themselves produce. The phenomenon is called quorum sensing, and is important when an infection propagates. Now, researchers at Linköping University in Sweden are showing how bacteria control processes in human cells the same way.
The results are being published in PLOS Pathogens with Elena Vikström, researcher in medical microbiology, as the main author.

How bacteria talk to each other and our cells

Bacteria can talk to each other via molecules they themselves produce. The phenomenon is called quorum sensing, and is important when an infection propagates. Now, researchers at Linköping University in Sweden are showing how bacteria control processes in human cells the same way.

The results are being published in PLOS Pathogens with Elena Vikström, researcher in medical microbiology, as the main author.

Filed under cells bacteria quorum sensing cell communication multicellular organisms neuroscience science

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Did bacteria spark evolution of multicellular life?
Bacteria have a bad rap as agents of disease, but scientists are increasingly discovering their many benefits, such as maintaining a healthy gut.
A new study now suggests that bacteria may also have helped kick off one of the key events in evolution: the leap from one-celled organisms to many-celled organisms, a development that eventually led to all animals, including humans.
Published this month in the inaugural edition of the new online journal eLife, the study by University of California, Berkeley, and Harvard Medical School scientists involves choanoflagellates (aka “choanos”), the closest living relatives of animals. These microscopic, one-celled organisms sport a long tail or flagellum, tentacles for grabbing food and are members of the ocean’s plankton community. As our closest living relative, choanos offer critical insights into the biology of their last common ancestor with animals, a unicellular or colonial organism that lived and died over 650 million years ago.
“Choanoflagellates evolved not long before the origin of animals and may help reveal how animals first evolved,” said senior author Nicole King, UC Berkeley associate professor of molecular and cell biology.

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Did bacteria spark evolution of multicellular life?

Bacteria have a bad rap as agents of disease, but scientists are increasingly discovering their many benefits, such as maintaining a healthy gut.

A new study now suggests that bacteria may also have helped kick off one of the key events in evolution: the leap from one-celled organisms to many-celled organisms, a development that eventually led to all animals, including humans.

Published this month in the inaugural edition of the new online journal eLife, the study by University of California, Berkeley, and Harvard Medical School scientists involves choanoflagellates (aka “choanos”), the closest living relatives of animals. These microscopic, one-celled organisms sport a long tail or flagellum, tentacles for grabbing food and are members of the ocean’s plankton community. As our closest living relative, choanos offer critical insights into the biology of their last common ancestor with animals, a unicellular or colonial organism that lived and died over 650 million years ago.

“Choanoflagellates evolved not long before the origin of animals and may help reveal how animals first evolved,” said senior author Nicole King, UC Berkeley associate professor of molecular and cell biology.

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Filed under animals evolution bacteria multicellular organisms choanos biology neuroscience science

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'Genomic CSI' Helps Contain a Killer

22 August 2012 

In June of last year, a 43-year old woman was admitted to the Clinical Center of the National Institutes of Health in Bethesda, Maryland, for a lung disease. Doctors knew she was carrying a highly resistant form of a deadly bacterium known as Klebsiella pneumoniae—although it didn’t make her sick—and they placed her in isolation. When the woman was discharged, no one else appeared to have become infected. A few weeks later, however, another patient was found to be carrying the bacterium, and over the next 3 months, 12 more intensive care patients contracted it. Six died as a direct result of the infection.

Doctors could not make sense of the outbreak with the usual methods: A survey of bed locations showed that the first patient had had no direct contact with any of the others and, in theory, Klebsiella might have been introduced into the hospital multiple times. So physicians turned to the bacterium’s genome for answers. The approach, known as genomic epidemiology, helped them track the path of the microbe, contain the disease, and save lives, according to a new study.

Tracking a killer. Full-genome sequencing revealed the movements of Klebsiella (shown) within one hospital. Credit: Image courtesy of Adrian Zelazny

Genomic epidemiology makes use of the fact that when bacteria divide, they accumulate mutations. As a result, the bacterial genome differs slightly—often by just one or two letters of genetic code, or base pairs—from one patient to the next. By fully sequencing the genomes of patients’ bacteria and finding these minute differences, researchers can track microbial movements with unprecedented precision. The technique has already been used to reconstruct the spread of methicillin-resistant Staphylococcus aureus (MRSA) around the world and to pinpoint the origin of a cholera outbreak in Haiti.

It also helped the doctors at the hospital in Bethesda. Comparing the genomes from all patients showed that the female patient admitted in June had indeed initiated the outbreak; the researchers showed that the bacteria had been transmitted from her to other patients three times independently. Apparently, transmission occurred in ways the researchers didn’t understand, says Tara Palmore, an infectious disease physician at the hospital. “When we realized there was more than met the eye, we started testing everyone in the hospital,” she says. That helped identify four more infected patients outside the intensive care unit, the scientists report online today in Science Translational Medicine. They were quickly isolated, which Palmore believes prevented further spread.

Just how the microbes were transmitted is still unclear. Palmore assumes that the bacteria mainly traveled on the hands of doctors. But the clinic had stationed a person outside the isolation rooms to make sure everyone who entered followed a hygiene regimen 24/7. That suggests that bacteria might have established colonies on surfaces or medical equipment and spread that way as well. “The conventional wisdom is that Klebsiellas do not really survive in the environment, but we found them in six sink drains and a ventilator,” Palmore says.

"This small study demonstrates the potential power of whole genome sequencing for outbreak investigation and surveillance," says Sharon Peacock, a microbiologist at the University of Cambridge in the United Kingdom who was not involved in the work. And infectious disease specialist Dag Harmsen of the University Clinic of Münster in Germany says it is "further proof that the time is ripe for using genomic sequencing of pathogens in a hospital setting." The paper also highlights the dangers of resistant Gram-negative bacteria like Klebsiella p., he adds. In many patients, the bacteria were not susceptible to any available antibiotic; not even to colistin, an old compound used only when all else fails. “This is even more dramatic than MRSA, because you have nothing left to treat the patients with,” Harmsen says. Since the outbreak, every patient at the hospital is checked for such dangerous pathogens; one more resistant Klebsiella case—although a different strain—has been found so far.

Genomic epidemiology could make it easier for hospitals to deal with similar outbreaks, Palmore says. “A lot of academic centers have the ability to do this now,” she says. The cost is becoming less of an issue; during last year’s outbreak, scientists still paid about $2000 per genome sequenced; now that would be closer to $500. But Peacock cautions that it still takes bioinformatics specialists several weeks to interpret the data. “This technology will not be applicable to routine clinical practice until automated interpretation tools become available.”

(Source: news.sciencemag.org)

Filed under bacteria disease genomic epidemiology genomics microbes neuroscience science Klebsiella pneumoniae

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Microbes manipulate your mind

Gut bacteria may influence thoughts and behaviour

The human gut contains a diverse community of bacteria that colonize the large intestine in the days following birth and vastly outnumber our own cells. These so-called gut microbiota constitute a virtual organ within an organ, and influence many bodily functions. Among other things, they aid in the uptake and metabolism of nutrients, modulate the inflammatory response to infection, and protect the gut from other, harmful micro-organisms. A study by researchers at McMaster University in Hamilton, Ontario now suggests that gut bacteria may also influence behaviour and cognitive processes such as memory by exerting an effect on gene activity during brain development.

Image: Brian Stauffer

Jane Foster and her colleagues compared the performance of germ-free mice, which lack gut bacteria, with normal animals on the elevated plus maze, which is used to test anxiety-like behaviours. This consists of a plus-shaped apparatus with two open and two closed arms, with an open roof and raised up off the floor. Ordinarily, mice will avoid open spaces to minimize the risk of being seen by predators, and spend far more time in the closed than in the open arms when placed in the elevated plus maze.

This is exactly what the researchers found when they placed the normal mice into the apparatus. The animals spent far more time in the closed arms of the maze and rarely ventured into the open ones. The germ-free mice, on the other hand, behaved quite differently – they entered the open arms more often, and continued to explore them throughout the duration of the test, spending significantly more time there than in the closed arms.

(Source: Guardian)

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Filed under microbes science neuroscience brain behavior psychology thinking bacteria

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The human microbiome: Me, myself, us
Looking at human beings as ecosystems that contain many collaborating and competing species could change the practice of medicine.
A human being is an individual who has grown from a fertilised egg which contained genes from both father and mother. A growing band of biologists, however, think this definition incomplete. They see people not just as individuals, but also as ecosystems. In their view, the descendant of the fertilised egg is merely one component of the system. The others are trillions of bacteria, each equally an individual, which are found in a person’s gut, his mouth, his scalp, his skin and all of the crevices and orifices that subtend from his body’s surface.
A healthy adult human harbours some 100 trillion bacteria in his gut alone. That is ten times as many bacterial cells as he has cells descended from the sperm and egg of his parents. These bugs, moreover, are diverse. Egg and sperm provide about 23,000 different genes. The microbiome, as the body’s commensal bacteria are collectively known, is reckoned to have around 3m. Admittedly, many of those millions are variations on common themes, but equally many are not, and even the number of those that are adds something to the body’s genetic mix.

The human microbiome: Me, myself, us

Looking at human beings as ecosystems that contain many collaborating and competing species could change the practice of medicine.

A human being is an individual who has grown from a fertilised egg which contained genes from both father and mother. A growing band of biologists, however, think this definition incomplete. They see people not just as individuals, but also as ecosystems. In their view, the descendant of the fertilised egg is merely one component of the system. The others are trillions of bacteria, each equally an individual, which are found in a person’s gut, his mouth, his scalp, his skin and all of the crevices and orifices that subtend from his body’s surface.

A healthy adult human harbours some 100 trillion bacteria in his gut alone. That is ten times as many bacterial cells as he has cells descended from the sperm and egg of his parents. These bugs, moreover, are diverse. Egg and sperm provide about 23,000 different genes. The microbiome, as the body’s commensal bacteria are collectively known, is reckoned to have around 3m. Admittedly, many of those millions are variations on common themes, but equally many are not, and even the number of those that are adds something to the body’s genetic mix.

Filed under science neuroscience biology biochemistry psychology bacteria diseases disorders

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Biologists try to engineer life that can survive on Mars and aid colonisation
With Nasa’s Curiosity Rover safely on Mars and ready  to search for signs of life, back on Earth attempts are underway to engineer bacteria that could thrive on the Red Planet.
A team of undergraduates from Stanford and Brown Universities are busy applying synthetic biology to space exploration, outfitting microbes to survive extreme Martian conditions and produce resources needed to sustain a human colony.
Though Mars is potentially a place where life may have survived at some point, it is not an especially friendly environment, and thriving there will not be easy — for humans or microbes. The average surface temperature of Mars is minus 80 degrees Fahrenheit, and the almost-nonexistent atmosphere is 95 percent carbon dioxide. Although  water exists in Mars’ ice caps and there’s some evidence that giant oceans once covered the planet, today it’s essentially a deep-frozen desert. Colonising Mars would be challenging and pricey.

Biologists try to engineer life that can survive on Mars and aid colonisation

With Nasa’s Curiosity Rover safely on Mars and ready to search for signs of life, back on Earth attempts are underway to engineer bacteria that could thrive on the Red Planet.

A team of undergraduates from Stanford and Brown Universities are busy applying synthetic biology to space exploration, outfitting microbes to survive extreme Martian conditions and produce resources needed to sustain a human colony.

Though Mars is potentially a place where life may have survived at some point, it is not an especially friendly environment, and thriving there will not be easy — for humans or microbes. The average surface temperature of Mars is minus 80 degrees Fahrenheit, and the almost-nonexistent atmosphere is 95 percent carbon dioxide. Although water exists in Mars’ ice caps and there’s some evidence that giant oceans once covered the planet, today it’s essentially a deep-frozen desert. Colonising Mars would be challenging and pricey.

Filed under Mars bacteria biology microorganisms science space neuroscience planetary environment

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Can bacteria fight brain cancer?
The thinking behind an approach that has caused trouble in California.
Last week, the Sacramento Bee reported that two neurosurgeons at the University of California, Davis, had been banned from research on humans after deliberately infecting three terminally ill cancer patients with pathogenic bacteria in an attempt to treat them. All three died, two showing complications from the infection. Nature explores what happened and the science behind it.

Can bacteria fight brain cancer?

The thinking behind an approach that has caused trouble in California.

Last week, the Sacramento Bee reported that two neurosurgeons at the University of California, Davis, had been banned from research on humans after deliberately infecting three terminally ill cancer patients with pathogenic bacteria in an attempt to treat them. All three died, two showing complications from the infection. Nature explores what happened and the science behind it.

Filed under bacteria brain cancer infection medicine neuroscience research science neurosurgery

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