Unusually large, bacteria-killing viruses discovered

Scientists have discovered hundreds of unusually large, bacteria-killing viruses with capabilities normally associated with living organisms.

The huge phages were found by scouring a large database of DNA generated from nearly 30 different environments, ranging from the guts of premature infants and pregnant women to a Tibetan hot spring, a South African bioreactor, hospital rooms, oceans, lakes and deep underground.

The phages -- short for bacteriophage because they "eat" bacteria -- are of a size and complexity considered typical of life, carry numerous genes normally found in bacteria and use these genes against their bacterial hosts.

The findings provide new insight into the constant warfare between phages and bacteria.

The study was done by scientists from the University of Melbourne and the University of California, Berkeley, who identified 351 different huge phages, all with genomes four or more times larger than the average genomes of viruses that prey on bacteria.

Among the discovery was the largest bacteriophage to date: its genome, 735,000 base-pairs long, is nearly 15 times larger than the average phage. This largest known phage genome is much larger than genomes of many bacteria.

"We are exploring Earth's microbiomes and sometimes unexpected things turn up," said Professor Jill Banfield, the senior author of the findings now published in Nature. "These viruses of bacteria are a part of biology, of replicating entities, that we know very little about."

Professor Banfield is now at Berkeley in earth and planetary science and environmental science, policy and management but did a significant portion of her work on the phages when she was in the School of Earth Sciences at the University of Melbourne.
 

These huge phages bridge the gap between non-living bacteriophage, on the one hand, and bacteria and Archaea (the diversity of bacteria). There definitely seems to be successful strategies of existence that are hybrids between what we think of as traditional viruses and traditional living organisms."Professor Jill Banfield 

The new findings also have implications for human disease. Viruses in general carry genes between cells, including genes that confer resistance to antibiotics. And since phages occur wherever bacteria and Archaea live, including the human gut microbiome, they can carry damaging genes into the bacteria that colonize humans.

"Some diseases are caused indirectly by phages, because phages move around genes involved in pathogenesis and antibiotic resistance," said Professor Banfield. "And the larger the genome, the larger capacity you have to move around those sorts of genes, and the higher the probability that you will be able to deliver undesirable genes to bacteria in human microbiomes."

Professor Banfield has been studying the diversity of bacteria for more than 15 years.

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Viruses could be the best bet for fighting antibiotic-resistant superbugs

Antibiotics won the battle against resistant bacteria, but they may not win the war.

You probably know that antibiotic-resistant bacteria, also known as superbugs, have hampered physicians’ ability to treat infections. You may also be aware that there has been a steep decline in the number of new antibiotics coming to market. Some headlines suggest humanity is doomed by antimicrobial resistance; even politician and governments have weighed in, comparing rising antimicrobial resistance to other popular crises such as climate change. Although I believe these assertions are exaggerated, antimicrobial resistance is a serious problem.

I am a physician scientist with a specialty in infectious diseases. I have been fascinated by the role that bacteria play in human health, and the potential for using viruses to treat bacterial infections.

What causes antimicrobial resistance?

One significant factor contributing to antimicrobial resistance is the excessive use of antibiotics. In the U.S., where antibiotics are widely available, some patients demand these drugs for many different illnesses. Many physicians appease their patients because they don't understand when and when not  to use them and because there is no regulatory structure to limit their use. Anyone with a prescription pad can prescribe any antibiotic to treat any condition and rarely, if ever, face any consequences. There are some efforts to reduce antibiotic use, but the scope of the problem in the U.S. remains large.

Some countries, such as Sweden, use incentives to encourage doctors to improve antibiotic uses. But there is no counterpart for this system in U.S. hospitals and clinics.

The problem goes beyond humans; 70 percent of all antibiotics are actually used on animals. This means that humans can be exposed to antibiotics by just handling animal products. The drumstick you are preparing for dinner might also have antibiotic-resistant bacteria tagging along.  

Once antimicrobial resistance develops in a bacterium, it doesn’t always go away. For example, methicillin-resistant Staphylococcus aureus (MRSA) evolved resistance to multiple different antibiotics; yet, despite efforts to reduce its spread by limiting the use of antibiotics that led to its emergence, MRSA still persists in hospitals and the community.

An alternative to antibiotics

Another reason for finding alternatives to antibiotics is that we share our microbes with the people and pets who live around us ; thus, others can acquire one of these superbugs without ever taking an antibiotic.

A not-so-obvious reason for developing new therapies is that our bodies are home to a large community of microorganisms, including bacteria, called our microbiome. These microorganisms are necessary to maintain our health. Those same antibiotics that kill harmful bacteria also kill the good ones.

There is an alternative to antibiotics, but it was dismissed by medicine years ago.

Antibiotics or wrong diet damage the good and bad bacteria flora living in the gut

The original phage therapy story

That alternative was something called phage therapy, which uses viruses that infect bacteria, called bacteriophages, to kill disease-causing bacteria. Bacteriophages, or phages, were used frequently in the early - and pre-antibiotic eras  between the 1920s and ‘40s to treat life-threatening infections.

But phage therapy had many disadvantages. The first was that phages were unpredictable. One type of phage might wipe out the bad bacteria in one individual but not another. So hospitals had to keep a broad collection of phages to kill disease-causing bacteria from all their patients. An antibiotic such as vancomycin, by comparison, predictably kills entire groups of bacteria.

Another downside is that phage collections require maintenance. So not only did hospitals have to keep a large variety of phages on hand, but they had to keep them in shape. So medicine chose antibiotics for convenience, and hadn’t looked back in any meaningful way, until recently.

Making a comeback?

So, why is phage therapy making a comeback? Antibiotic resistance is an obvious answer, but doesn’t explain the full story.

As a specialist in infectious diseases, I have been interested in phage therapy as long as I can remember, but only recently have I felt comfortable saying this out loud. Why? A physician might be considered a “quack” just for mentioning phage therapy because the early attempts were neither a rousing success or a colossal failure. Like any therapeutic, it had its strengths and weaknesses.

However, now scientific advances can guide us toward which phage is best for destroying a particular microbe. With the rising antimicrobial resistance crisis, physicians and scientists have a well-timed opportunity to work together to develop effective phage therapies.

The proof of this comes from recent landmark phage therapy cases. The successful treatment of a physician with a life-threatening infection and a grave prognosis caused by a multi-drug resistant- a life- threatening infection and a grave prognosis caused by a multi-drug resistant bacterium at my institution serves as a great example. Another pivotal case circulating in popular media has kept this trend going. We physicians may be able to treat just about any disease-causing bacterium; it is just a matter of finding a suitable phage.

A big part of phage therapy research is devoted to “phage hunting ,” where we microbiologists scour the soil, the oceans and the human body to identify phages with the potential to kill the bacteria that ail us. While the pace of these studies has been slow, the new research is revealing the therapeutic potential of phages in medicine.

You might think that with all the phage hunting and landmark cases that we would start using phage therapy all the time, but we don’t.

Bacteriophages target only specific stains of bacteria

The case for using phages

One advantage of antibiotics is that since they have been used for decades, we know a lot about their safety. Physicians make simple calculations every day about the risk-benefit ratio of using antibiotics, but aren’t equipped to make the same calculations about phages. Does anyone really want a doctor injecting them with a virus to cure a bacterial infection? I doubt that would be anyone’s choice when the question is posed that way.

But, remember that phages are natural. They’re on every surface of your body. They are in the ocean and soil, and in your toilet and sink. They are literally everywhere. Thus, putting a phage into your body to kill a bacterium quite frankly is something that nature does to us every single day, and as far as we know, we are no worse for the wear.

Phages are estimated to kill half the world's bacteria every 48 hours and are probably the most potent antibacterial agents out there. Is there really a compelling reason to be concerned when a doctor gives us a phage instead of us acquiring that same phage from our sink at home? Only time will tell. Unfortunately, as antimicrobial resistance continues to rise, time may not be on our side.

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New device spots bacterial infection faster

Scientists from the Indian Institute of Technology-Kanpur (IIT-K) have built a new sensor that can detect bacterial infection in food and water in just 15-20 minutes, much faster than traditional laboratory tests.

“Pathogenic bacterial infection is one of the biggest causes of death, and a fast response time is much needed for timely detection and subsequent cure of bacterial infection,” said Saurabh Mani Tripathi, a physicist at IIT-K.

The device, developed with collaborators from the Photonics Research Centre at the University of Quebec in Outaouais works over wide temperature range to quickly and cost-effectively identify the potentially deadly Escherichia coli (E. coli) bacteria.

Found in the environment, food and intestines of people and animals, most strains of E. coli are harmless. But some kinds of E. coli can cause diarrohea, while others cause urinary tract infections, respiratory illness and pneumonia, and other illnesses, according to the US Centres for Disease Control and Prevention.

“Using currently available technologies, which are mostly based on amplification of the sample, it takes several hours to days to detect the presence of bacteria. A fast and accurate detection alternative is, therefore, preferable over the existing technology,” Tripathi noted.

Faster tests for the bacteria could lead to faster treatment of patients, as well as to cheaper and easier environmental monitoring, he said.

The new sensor uses bacteriophages — viruses that can naturally latch onto and kill bacteria.

The viruses are bonded to the surface of an optical fibre and will grab E. coli bacteria from a sample and keep them attached.

When a beam of light strikes the surface, the presence of E. coli shifts the wavelength in a telltale sign of bacterial contamination.
One of the challenges of using optical fibres for bacteria detection is that temperature changes can alter the optical properties of the materials.

Sensors are therefore often designed to work at a particular temperature and give inaccurate readings if the sample gets much hotter or colder.

Tripathi and his colleagues overcame this challenge by adding an additional optical component and in effect canceling out temperature-induced shifts.

Their device, in the journal Optics Letters, is temperature insensitive over an approximately 20-degree Celsius, starting at room temperature and going up to 40-degrees Celsius.

The temperature insensitivity makes the sensor more practical for outdoor applications, like on-site monitoring of water reservoirs, Tripathi said.

He also noted that the food industry and pathology labs are other possible users of the new sensors.

The researchers said that the sensor can be modified to detect other strains of bacteria by changing the bacteriophage.

The research group is currently collaborating with Security and Protection International, a Canadian company, to explore commercialization of their device.

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