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International Human Microbe Program Looks Ahead – ScienceInsider

Posted on by charlie

Indeed, Sharp said at the meeting, patients who come to Cleveland Clinic for treatment of inflammatory bowel disease express their own concerns about such approaches, which could include the use of probiotics, the consumption of live microorganisms, to treat intestinal and other maladies. “Many patients are worried about manipulating their gut microbiota,” Sharp said, adding that “they see these kinds of studies through the lens of genetically modified foods. They worry that tampering with the gut microbiome could lead to irreversible effects.”Sharp also urged the microbiome research community, along with funding agencies, to start doing more public outreach to counter the often “grossly misleading” statements made by companies that sell probiotic products, including claims that probiotics can cure cancers and treat autism spectrum disorders. “Most of what people know about this area of research comes from these retailers,” Sharp said. “We should not be relying on these companies to put out the first messages about this area of research.”

This is an interesting article on what’s next for human microbiome research. It lists some of the companies getting involved (great!) and some talk about what will happen to jumpt start a whole new round of funding.

What was surprising to me was how little money was put into the multi-year programs (total $167M). Prehaps I don’t have a feel for what’s a lot of money in research.

Read International Human Microbe Program Looks Ahead – ScienceInsider.

Science/The Narrative

Microbiome sequencing offers hope for diagnostics : Nature News & Comment

Posted on by charlie

“Jonathan Eisen [@phylogenomics], a microbiologist at University of California, Davis, is worried that microbiome research will eventually encounter the same backlash. “Without a doubt we are running into some of the same problems as the Human Genome Project,” he says. “There are many people who have oversold the human microbiome as the cause or cure of everything.” Eisen worries that although numerous connections have been discovered between the microbiome and diseases, it is usually unclear whether the microbes caused the conditions or merely exploited a new environment.“There’s sensitivity about the expected returns,” says David Relman, who studies infectious disease at Stanford University in Palo Alto, California. “We need to be grounded about what it is we’ll be able to gain at what point in time. I think the shorter-term gains may be around diagnostics, and novel ways of classifying both health and disease.”

This article has some great quotes (like above) on caution about the benefits of microbiome sequencing. I also agree with the writer, Ed Yong (@edyong209), that, yes, learning more about the human microbiome is amazing, but we need to not make outlandish claims as to what we will do with that understanding.

Ed mentioned some probiotic studies (an area I have been reading a lot about) and that hype pre-dates all the microbiome hype.

My comment: let’s learn all we can about the microbiome. Let’s see what we learn before we make as outlandish claims as we did in the 80s about knowing all about our genome.

Spot, on, Ed. Thanks for calling this out.

Read Microbiome sequencing offers hope for diagnostics : Nature News & Comment.

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Dangerous C. difficile infections soar in US, but Massachusetts hospitals have cut germ’s spead – The Boston Globe

Posted on by charlie

“A life-threatening germ that causes diarrhea and spreads easily from doctors’ offices to hospitals and nursing homes has climbed to historic highs nationally, federal disease trackers warned Tuesday, as they pointed to efforts in Massachusetts that have helped slow the rate of infections here.”

More on this nasty bug. It’s now getting headlines.

Read this article…

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A human gut microbial gene catalogue established by metagenomic sequencing : Nature

Posted on by charlie

“Beyond providing the global view of the human gut microbiome, the extensive gene catalogue we have established enables future studies of association of the microbial genes with human phenotypes and, even more broadly, human living habits, taking into account the environment, including diet, from birth to old age. We anticipate that these studies will lead to a much more complete understanding of human biology than the one we presently have.”

I feel kinda cheezy for quoting the very last paragraph of this long and interesting paper. But there is so much to like about it, I didn’t know which to quote.

Basically, these folks sequenced the bacteria on fecal samples from a lot of healthy folks, and folks with IBD (inflammatory bowel disease), ulcerative colitis, obesity, and who were overweight.

They confirmed that each of these states have their own particular microbiome profile. But they also did a ton of metagenomic analysis, even establishing what the “minimal microbiome” is. And in their analysis they describe what this minimal microbiome mean to human health and physiological processes.

Quite fascinating.

And the reason they are building this catalog (3.3 million microbial genes!) is that they will continue studying the subjects who donated the samples. And this is a good addition to the International Human Microbiome Consortium.

And of note, about half the authors of this work are from BGI-Shenzen, the über-sequencing institute, but the rest of the collaborators are from Europe and some from the large European sequencing centers. This reminds me of an article about BGI-Shenzen that discusses how the center is building up amazing collaborations outside of China. This is proof of what those collaborations can yield. We all gain, and it’s so much better than trying to do it alone, for the glory of China.

via A human gut microbial gene catalogue established by metagenomic sequencing : Article : Nature.

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Genome Sequence of E. coli O104:H4 Leads to Rapid Development of a Targeted Antimicrobial Agent against This Emerging Pathogen – PLoS ONE

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“A recent widespread outbreak of Escherichia coli O104:H4 in Germany demonstrates the dynamic nature of emerging and re-emerging food-borne pathogens, particularly STECs and related pathogenic E. coli. Rapid genome sequencing and public availability of these data from the German outbreak strain allowed us to identify an O-antigen-specific bacteriophage tail spike protein encoded in the genome. We synthesized this gene and fused it to the tail fiber gene of an R-type pyocin, a phage tail-like bacteriocin, and expressed the novel bacteriocin such that the tail fiber fusion was incorporated into the bacteriocin structure. The resulting particles have bactericidal activity specifically against E. coli strains that produce the O104 lipopolysaccharide antigen, including the outbreak strain. This O-antigen tailspike-R-type pyocin strategy provides a platform to respond rapidly to emerging pathogens upon the availability of the pathogen’s genome sequence.”

When an outbreak in pathogenic E coli broke out in Germany last summer, scientists were able to sequence the genome in a few hours on a Life Technologies Ion PGM sequencer. This speed gave the public health official insight into what they were dealing with.

This paper linked to below, was able to then take the sequence and rapidly create a strain-specifc bacteriocin-phage bacteriocide. And, based on the submission date, they did this in a few months.

This points to a promising future where we sequence the pathogen the day we discover it and rapidly create targeted bactericides. Cool. And our kids will look back and wonder why were were trying carpet-bomb bacteria with rapidly useless antibiotics. This is the post-antibiotic age.

via PLoS ONE: Genome Sequence of E. coli O104:H4 Leads to Rapid Development of a Targeted Antimicrobial Agent against This Emerging Pathogen.

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Bacterial genomics: A new source of antimicrobial targets : Nature Reviews Microbiology

Posted on by charlie

“Bacterial clone-based genome sequencing frequently results in gaps, which harbour hypothetical genes of unknown function. Sorek and colleagues show that these gaps contain a vast array of genes encoding proteins that are toxic to the sequencing host (Escherichia coli), including previously uncharacterized restriction enzymes, toxin–antitoxin systems and non-coding RNAs.”

Of course, to me, this is very clever, having never thought about this. Yes, we always knew that some sequences were unclonable because of incompatibility with the cloning vector. But the cleverness is to actually look for those gaps as potential anti micribials. That’s one of those amazing “Duh”s that sometimes happen when things are right under our nose.

Only sucky thing is that the article is CLOSED ACCESS. Fail.

via Access : Bacterial genomics: A new source of antimicrobial targets : Nature Reviews Microbiology (subscription required).

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A Method for Generation Phage Cocktail with Great Therapeutic Potential – PLoS ONE

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“Bacteriophage could be an alternative to conventional antibiotic therapy against multidrug-resistant bacteria. However, the emergence of resistant variants after phage treatment limited its therapeutic application. Our data showed that the phage cocktail was more effective in reducing bacterial mutation frequency and in the rescue of murine bacteremia than monophage suggesting that phage cocktail established by SBS method has great therapeutic potential for multidrug-resistant bacteria infection.”

Biologic warfare at the bacterial level. In some developed countries antibiotic misuse has caused the rapid development of antibiotic-resistant bacteria. Bacteriophage therapy has therefore taken a more important role. Except, it has its issues. In this paper, they work to avoid phage resistance with a multi-phage approach.

Read this article…

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Macro and Micro Diversity of Clostridium difficile Isolates from Diverse Sources and Geographical Locations – PLoS ONE

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“Clostridium difficile has emerged rapidly as the leading cause of antibiotic-associated diarrheal disease, with the temporal and geographical appearance of dominant PCR ribotypes. We have undertaken a breadth genotyping study using multilocus sequence typing (MLST) analysis of 385 C. difficile strains from diverse sources by host (human, animal and food), geographical locations (North America, Europe and Australia) and PCR ribotypes. Results identified 18 novel sequence types (STs) and 3 new allele sequences and confirmed the presence of five distinct clonal lineages generally associated with outbreaks of C. difficile infection in humans.”

A broad survey to understand the nature of this pesky and increasingly common pathogen.

Read this article…

Innovation/Links of note/Science/Strategy

Broad Institute Gets $32.5 Million to Map Cell Circuits – ScienceInsider

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“The Broad isn’t alone: Mount Sinai School of Medicine in New York City, the Allen Institute for Brain Science in Seattle, the Salk Institute in San Diego, and University of California, San Diego, are also launching major efforts to study cell circuitry, says UCSD computational biologist Trey Ideker. He suggests that eventually these groups should form a “big, coordinated science project” so that they can divide up the task of mapping circuits in different cell types. “This is a very big goal and in a sense the logical successor to the Human Genome Project,” Ideker says.”

Mapping cellular circuits – very interesting.

Read this article…

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Two-Drug Antimicrobial Chemotherapy: A Mathematical Model and Experiments with Mycobacterium marinum – PLoS Pathogens

Posted on by charlie

This paper is trying to measure and model the effectiveness of multi-drug antimicrobial chemotherapy.

Antibiotics are notorious for losing effectiveness as the target microbe gains resistance to that single antibiotic. Being able to treat microorganism with multiple drugs is sometimes the only way to manage the disease – as in HIV or TB.

But to be able to create better multi-drug cocktails, we’ll need to better model the contributions of each component.

This paper seeks to show how to measure and prove the effectiveness of the component sin a two-drug system. But I am wondering how we’ll do the same for more than two drugs (HIV anti-viral therapy has at least three components).

Read this article…