JUST THE FAQS: Top Scientists Around The Nation Call For A Unified Microbiome Initiative

JUST THE FAQS: Top Scientists Around The Nation Call For A Unified Microbiome Initiative

JUST THE FAQS: Top Scientists Around the Nation Call for a Unified Microbiome Initiative

Writing in the journal Science this week, a group of top microbiome researchers from around the country, including UC San Diego School of Medicine’s Rob Knight, PhD, and Pieter Dorrestein, PhD, lay out a proposal for what they call a Unified Microbiome Initiative. This latest post in the JUST THE FAQS series takes a look at what that means and why it’s important.

What is the Unified Microbiome Initiative?

The proposed Unified Microbiome Initiative is a national effort to fund, coordinate and accelerate microbiome research — the study of the microbial communities (bacteria, viruses, etc.) that live in, on and around us.

Why do we need this?

According to the authors of this proposal, the microbiome field currently lacks many of the technologies and resources required to take the research from where it is today (i.e., mostly describing what microbes are living where) to the next level — understanding exactly how microbes influence our health and how we might be able to manipulate them to our benefit.

“… such knowledge could transform our understanding of the world and launch innovations in agriculture, energy, health, the environment and more,” the authors write in the proposal.

This ambitious undertaking cannot be accomplished by individual laboratories working in isolation. Developing these tools requires new collaborations between physical, life, and biomedical sciences, engineering and many other disciplines. Advancing this nascent field also depends on attracting, training and supporting multidisciplinary networks of scientists and engineers, all things that could be accomplished through a concerted national effort, Knight, Dorrestein and their co-authors say.

Wait, what is the microbiome again?

Your body contains as many as 10 times more microbial cells than human cells. Even crazier, that adds up to two to 20 million microbial genes, compared to your 20,000 or so human genes. By that measure, you could say you’re actually only about 10 percent human.

Researchers like Knight, Dorrestein and their teams are now mapping the other 90 percent — the collections of microbial genes (“microbiomes”) found in our guts, mouths, skin, and many other locations on and around the body. They’re finding that the makeup of our gut microbiomes is associated with a rapidly growing list of diseases and conditions: food allergies, obesity, inflammatory bowel disease and colon cancer, rheumatoid arthritis, atherosclerosis, asthma, perhaps even anxiety, depression and autism. But researchers don’t yet know why these associations occur, whether they are cause or effect, and whether or not we could use gut microbiome readouts for medical predictions, diagnoses or treatments.

And that’s just the gut microbiome. Imagine what researchers will find when they dive as deeply into the microbiomes of the rest of our bodies, as well as our homes, the ocean and other environments. That’s why Knight, Dorrestein and many other experts are today calling for a collaborative, well-supported United Microbiome Initiative.

To learn more about Knight’s and Dorrestein’s microbiome work, check out: Antibiotic Resistance in Microbiomes, Despite Isolation from Western Civilization

3D Human Skin Maps Aid Study of Relationships Between Molecules, Microbes and Environment

Pictured: Staphylococcus aureus bacteria. Source: NIAID

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Bilirrubin: given in 2°,3°T, high risk or indirect hyperBb and kernicterus in premies

Warfarin: increases toxicity: bleeding

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Aminopenicillins (Amoxicillin, Ampicillin)

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L  isteria monocytogenes

A  typicals (Mycoplasma, Chlamydia)

M RSA (except Ceftaroline, 5°G)

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image

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A group of scientists have just published their work in CellPress on synthesising novel phages using common viral structures (Figure 1), to target a range of bacterial hosts. Anyone who frequently reads my posts will be fully aware of what bacteriophages are, however put simply phages are viruses that target bacteria (Figure 1). Currently a lot of research is going into these little guys to utilise them for both therapeutic and diagnostic purposes. 

image

Figure 1. Image depicts a transmission electron micrograph of a phage (left) and a diagrammatic representation of the phage on the (right) showing all the major components that make up the protein coat.

Phages have an elaborate protein coat that surrounds their DNA cargo (contained within the head, Figure 1). They scan their surrounding environment for potential ‘prey’ by using their tail fibres to interact with their cognate receptors. The diversity of receptors is immense and many still go unidentified even for well characterised phages. Once a target is found, the baseplate then irreversibly attaches to the cell wall of the bacteria and the DNA can be transferred into the cytoplasm of the cell. 

Unlike current therapeutics, the sheer diversity between phages means that they are highly specific with limited host ranges to the species or even strain level. As a result, for phage therapy to be effective, a cocktail of phages needs to be employed to target a wide range of potential bacterial hosts. To improve the host ranges of phage groups such as this one are trying to synthesis novel structures from existing phages - much like how Frankenstein stitched together a new human body from pre-existing parts (Figure 2). 

image

Figure 2. Simplified image showing how bacterial components can be shuffled between genomes of related phages with different host ranges. 

Innovatively, this group used a well characterised yeast-based (Saccharomyces cerevisiae) platform for capturing phage genomes to allow their genetic manipulation (Figure 3). Phage genomes could then be inserted into a yeast artificial chromosome (YAC) then manipulated. Yeast are fairly easy to genetically modify by homologous-recombingation, making this system far easier to employ than other methods. The YAC was then recovered and transformed into the normal host bacteria, allowing the generation of new phage particles. Unlike other methods phage generated via this method were relatively easy to reboot back into active viral particles.

image

Figure 3. Illustration of the genetic manipulation of phage DNA to generate hybrid phages with altered host ranges. 

The group managed to show that by swapping modular components such as tail fibres between phages, new host specificity could be generated. Thus illustrating that gene swapping can overcome strain or species barriers if the need arises. This work will hopefully lead way to further improve phage therapy and decrease the persistent need for the identification of novel phages. Further work needs to be done on increasing the scope of their work, but they have created a framework that will hopefully be able to reboot more synthetic phages.

“Our results show that common phage scaffolds can be re-targeted against new bacterial hosts by engineering single or multiple tail components. This capability enables the the construction of defined phage cocktails that only differ in their host range determinants and can be used to edit the compositions of microbial consortia and/or treat bacterial infections.” - Ando et al, 2015

Sources:

Engineering Modular Viral Scaffolds for Targeted Bacterial Population Editing, 2015. Ando, H., Lemire. S., Pires. D.P., Lu. T.K., Cell Systems , Volume 1 , Issue 3 , 187 - 196  

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