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Some researchers are now testing to see if phage therapy  could be a possible treatment for some conditions, such as chronic sinusitis and wound infections. Phage therapy, which uses bacteriophages, was neglected for decades (except for Russia and the Republic of Georgia), but their use is again being studied as an alternative to antibiotics. A bacteriophage is a virus that lives within a bacterium, replicating itself, and eventually destroys the bacteria. The term is from "bacteria" and the Greek "phagein" which means to devour, so think of them as "bacteria eaters". Phages only attack specific types of bacteria (they are "bacterium specific"), so they’re unlikely to harm the normal microbiome (community of microbes) or any human cells.

I've been posting about the beneficial bacteria Lactobacillus sakei that treats chronic sinusitis, as well as some other probiotic (beneficial) bacteria that people have reported success with (see The One Probiotic That Treats Sinusitis). Most people contacting me or commenting have reported success with L. sakei products, but there is a group for whom L. sakei and other probiotics haven't helped. Why? And what can be done? Perhaps their sinuses are missing still unknown "keystone" species (very important microbial species for health). Or perhaps they have bacterial biofilms that even Lactobacillus species that are viewed as anti-biofilm cannot overcome. Perhaps phage therapy might help these people? 

Phage therapy is currently being tested by researchers in the treatment of chronic sinusitis in Australia. The video Antibiotic Resistance discusses phage therapy for sinusitis starting at 23:30. Looks promising.

And a write-up about the sinusitis phage therapy research from the Australian newspaper The Sydney Morning Herald: Medicine turns to bacteriophage therapy to beat superbugs

An arcane therapy for bacterial infections that dwelled behind the Iron Curtain for decades is making a comeback in Western medicine as a potential white knight against superbugs. Phage therapy involves infecting patients with viruses known as bacteriophages, which are the natural predators of bacteria, to kill the germs that antibiotics cannot.  ...continue reading "Phage Therapy May Help Sinusitis Sufferers"

The microbes living on healthy human skin include bacteria, fungi, and viruses...but 90% of the viruses found on healthy skin in this study are unknown to researchers - thus "viral "dark matter". The skin virome  is the population of viruses on the skin. It turns out that most of the viruses on healthy skin are phage viruses. called bacteriophages.They infect bacteria and may take up residence within bacteria. From Science Daily:

90 percent of skin-based viruses represent viral 'dark matter,' scientists reveal

Scientists in recent years have made great progress in characterizing the bacterial population that normally lives on human skin and contributes to health and disease. Now researchers from the Perelman School of Medicine at the University of Pennsylvania have used state-of-the-art techniques to survey the skin's virus population, or "virome." The study, published in the online journal mBio last month, reveals that most DNA viruses on healthy human skin are viral "dark matter" that have never been described before. The research also includes the development of a set of virome analysis tools that are now available to researchers for further investigations.

Researchers and the public are increasingly aware that microbes living on and inside us -- our "microbiomes" -- can be crucial in maintaining good health, or in causing disease. Skin-resident bacteria are no exception. Ideally they help ward off harmful infections, and maintain proper skin immunity and wound-healing, but under certain circumstances they can do the opposite.

"Until now, relatively little work has been done in this area, in part because of the technical challenges involved. For example, a skin swab taken for analysis will contain mostly human and bacterial DNA, and only a tiny amount of viral genetic material -- the proverbial needles in the haystack." 

Their analysis of samples from 16 healthy individuals revealed some results that were expected. The most abundant skin-cell infecting virus was human papilloma virus, which causes common warts and has been linked to skin cancers. However, most of the detected DNA from the VLPs did not match viral genes in existing databases. "More than 90 percent was what we call viral dark matter -- it had features of viral genetic material but no taxonomic classification," Grice said. That came as a surprise, although of course it highlighted the importance of mapping this unexplored territory.

The findings also clearly linked the skin virome to the skin microbiome: Most of the detected viral DNA appeared to belong to phage viruses, which infect and often take up long-term residence within bacteria. And when Grice and colleagues sequenced skin bacterial DNA from the same 16 subjects, they found that it often contained tell-tale marks -- called CRISPR spacers -- of prior invasion by the same phage viruses.

The results also showed that the skin virome varies considerably depending on the body site. Grice's team took swabs from the palm, the forehead, the armpit, the navel, and other sites, and found, for example, that the virome was most diverse in the crook of the arm, a site that is intermittently exposed and occluded.

A topic that is rarely mentioned is the human virome (the collection of resident viruses in the human body). We all have many viruses, but almost nothing is known about them.This is an introductory article about the human virome. From the January 11, 2014 Science News:

The vast virome

 The microbiome — what scientists refer to as the collection of bacteria, fungi and other single-celled organisms that live in and on the body — has been a hot research topic for more than a decade. But bacteria aren’t the only microbes with which we humans share space.

The most abundant inhabitants of what many researchers are calling “the human ecosystem” are the virusesViruses are deceptively simple organisms consisting of genetic material packed in a protein shell. They are tiny and can’t replicate on their own, relying on human or other cells to reproduce.

And yet, scientists estimate that 10 quintillion virus particles populate the planet. That’s a one followed by 31 zeros. They outnumber bacteria 10-to-1 in most ecosystems. And they’re ubiquitous in and on humans.

Pérez-Brocal and others are learning that viruses, once seen only as foreign invaders that make people sick, are an integral part of human biology. Some cause major diseases, including influenza, AIDS and some cancers. Others, conversely, may promote health. Some may even help us gauge how well the human immune system works.

The study of people’s resident viruses, known collectively as the human virome, is “a whole new frontier in the understanding of humans,” and could become important for the future of medicine, says Forest Rohwer, an environmental microbiologist at San Diego State University.

Rohwer’s research indicates that viruses are part of the human defense system. Mucus studded with bacteria-infecting viruses called bacteriophage, or phage, may help protect host cells from invasive microbes, he and his colleagues reported June 25 in the Proceedings of the National Academy of Sciences. 

“We know a lot about the bacteria that inhabit humans,” says David Pride, an infectious disease doctor at the University of California, San Diego. In comparison, “we know absolutely nothing about the viruses.” Not that scientists haven’t been interested in viruses. Until recently there was just no good way to identify them, an important first step toward understanding the biology of health and disease. As a consequence, virome research is in its infancy.

Researchers have gotten a head start on cataloging bacterial denizens of the body because all bacterial cells contain a version of the 16S ribosomal RNA gene. Virus hunters aren’t so lucky. There is no analogous virus-identification tag. Instead, to look for viruses, researchers must sequence hundreds of thousands of bits of DNA from a sample — skin swabs, saliva, feces or mucus, for example. Scientists have gotten really good at generating these DNA sequences; the trick is figuring out what they are.

Every time Frederic Bushman samples a new person’s virome, he says, he finds new viruses. A microbiologist at the University of Pennsylvania Perelman School of Medicine in Philadelphia, Bushman has shown that no two people’s gut viruses are exactly alike. But once a person has picked up a community of bacteria-infecting phage, it tends to stick around. Fully 80 percent of the viruses present when the researchers first started tracking one man’s virome were still there more than two years later.

Maybe researchers can use bacteriophage to shape the human microbiome in healthier ways. Using phage to control bacteria is a resurgence of an old idea. In the 1920s, doctors in the former Soviet Union and other Eastern European countries began using phage to treat specific bacterial infections. Unlike antibiotics, which kill bacteria indiscriminately, phage target only certain microbes for destruction.

“Healthy subjects are just loaded with viruses,” Wylie says. Even viruses known to cause diseases such as the common cold were found in healthy kids. That makes it difficult to determine whether a particular virus is really making someone sick.

Some viruses previously thought innocent may cause harmTo figure out which viruses are friends, foes or neutral passengers on the human body, scientists first need to identify them. Researchers still aren’t very good at recognizing new viruses, says Brian Jones, a molecular biologist at the University of Brighton in England. 

Based on what researchers have learned so far about the virome, Jones is convinced that viruses and other microbes “should be viewed as a part of us rather than something that lives in or on us.” They are part of the puzzle, the intricate ecosystem composed of human and microbial cells, all pushing and pulling at one another and subject to local conditions, such as diet and environment.

New discoveries of what is going on in our intestines, plus a new vocabulary to understand it all. Yes, it all is amazingly complex. Bottom line: we have complex communities (bacteria, bacterial viruses or bacteriophages, etc.) living and interacting in our intestines. And only with state-of-the-art genetic analysis (DNA sequencing) can we even "see" what is going on. I highlighted really important items in bold type. From Medical Xpress:

Researchers uncover new knowledge about our intestines

Researchers from Technical University of Denmark Systems Biology have mapped 500 previously unknown microorganisms in human intestinal flora as well as 800 also unknown bacterial viruses (also called bacteriophages) which attack intestinal bacteria.

"Using our method, researchers are now able to identify and collect genomes from previously unknown microorganisms in even highly complex microbial societies. This provides us with an overview we have not enjoyed previously," says Professor Søren Brunak who has co-headed the study together with Associate Professor Henrik Bjørn Nielsen.

So far, 200-300 intestinal bacterial species have been mapped. Now, the number will be more than doubled, which could significantly improve our understanding and treatment of a large number of diseases such as type 2 diabetes, asthma and obesity.

The two researchers have also studied the mutual relations between bacteria and virusesPreviously, bacteria were studied individually in the laboratory, but researchers are becoming increasingly aware that in order to understand the intestinal flora, you need to look at the interaction between the many different bacteria found.

And when we know the intestinal bacteria interactions, we can potentially develop a more selective way to treat a number of diseases. "Ideally we will be able to add or remove specific bacteria in the intestinal system and in this way induce a healthier intestinal flora," says Søren Brunak.

From Science Daily:

Revolutionary approach to studying intestinal microbiota

Analyzing the global genome, or the metagenome of the intestinal microbiota, has taken a turn, thanks to a new approach to study developed by an international research team. This method markedly simplifies microbiome analysis and renders it more powerful. The scientists have thus been able to sequence and assemble the complete genome of 238 intestinal bacteria, 75% of which were previously unknown. 

Research carried out in recent years on the intestinal microbiota has completely overturned our vision of the human gut ecosystem. Indeed, from "simple digesters" of food, these bacteria have become major factors in understanding certain diseases such as obesity, type 2 diabetes, or Crohn's disease. Important and direct links have also been demonstrated between these bacteria and the immune system, as well as with the brain. It is estimated that 100,000 billion bacteria populate the gut of each individual (or 10 to 100 times more than the number of cells in the human body), and their diversity is considerable, estimated to around a thousand different bacterial species in the intestinal human metagenome. However, because only 15% of these bacteria were previously isolated and characterized by genome sequencing, an immense number of the microbial genes previously identified still need to be assigned to a given species.

An analysis of 396 stool samples from Danish and Spanish individuals allowed the researchers to cluster these millions of genes into 7381 co-abundance groups of genes. Approximately 10% of these groups (741) corresponded to bacterial species referred to as metagenomic species (MGS); the others corresponded to bacterial viruses (848 bacteriophages were discovered), plasmids (circular, bacterial DNA fragments) or genes which protected bacteria from viral attack (known as CRISPR sequences). 85% of these MGS constituted unknown bacteria species (or ~630 species).

Using this new approach, the researchers succeeded in reconstituting the complete genome of 238 of these unknown species, without prior culture of these bacteria. Living without oxygen, in an environment that is difficult to characterise and reproduce, most of these gut bacteria cannot be cultured in the laboratory. 

The authors also demonstrated more than 800 dependent relationships within the 7381 gene co-abundance groups; this was the case, for example, of phages which require the presence of a bacterium to survive. These dependent relationships thus enable a clearer understanding of the survival mechanisms of a micro-organism in its ecosystem.