Immunotherapy—Don’t Forget the Microbiome

Bacteria make you sick. The idea that bacteria cause illness has become ingrained in modern society, made evident by every sign requiring employees to wash their hands before leaving a restroom and the frequent food recalls resulting from pathogens like E. coli. But a parallel idea has also taken hold. As microbiome research continues to reveal the important role that bacteria play in human health, we’re starting to see the ways that the microbiota of the human body may be as important as our genes or environment.

The story of how our microbiome affects our health continues to get more complex. For example, researchers are now beginning to understand that the composition of bacteria residing in your body can significantly impact the effects of therapeutic drugs. This is a new factor for optimizing drug response, compared to other considerations such as diet, interaction with other drugs, administration time and comorbidity, which have been understood much longer.

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5 of Our Favorite Blogs from 2018

We have published 130 blogs here at Promega this year (not including this one). I diligently reviewed every single one and compiled a list of the best 8.5%, then asked my coworkers to vote on the top 5 out of that subset. Here are their picks:

1. The Amazing, Indestructible—and Cuddly—Tardigrade

No surprises here, everyone loves water bears. Kelly Grooms knows what the people want.

The face of a creature that is nigh un-killable.

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Predicting the Future with Dirty Diapers

Microbiome research is booming right now, with more and more evidence that our personal health and environment are shaped and influenced by the microbes we harbor and encounter. One area of study I find particularly interesting is how the microbiome we acquire at birth affects our long-term health.

A flood of new findings have emerged related to infant microbiome research, leaving parents like me scratching their heads about whether the secrets to our children’s future health may exist in the seemingly endless stream of dirty diapers we change.

The human microbiome evolves and develops in utero and then during and after delivery is colonized by bacteria encountered during exposure to the external environment. The initial composition of microbes an infant is populated with influences their lifelong microbiome signature and can be influenced by many factors along the way, including the microbiome community of the mother, use of antibiotics or other antibacterial substances, breastfeeding, C-section birth. These variables have been correlated with disruption of the infant microbiome and associated with differences in cognitive development and the development of disease, such as asthma and allergies.

In general, these correlations are discovered by taking a fecal sample from an infant and analyzing the DNA sequences of the bacteria present. The microbiome composition of the individual is then compared against different individual characteristics (such as presence or absence of a disease) at the time of the sample and/or at later points in time. Finally researchers look for statistically significant patterns among individuals with similar characteristics or microbiome communities. This type of study can reveal associations between the microbiome and individual traits, but further experiments are needed to show causation.

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The Power of One: Revealing Microbial Dark Matter Using Single-Cell Sequencing

abstract digital backgroundMicroorganisms; they are the most abundant form of life. They are all around us, silent, unseen and undetected. The number of ‘species’ of archaea and bacteria climbs every year and is predicted to rise well past one million (1). Despite their abundance, we know very little about all but a small fraction of these diverse cellular life forms because we are unable to cultivate most in a laboratory setting. In fact, 88% of all our microbial isolates belong to just four bacterial phyla (Proteobacteria, Firmicutes, Actinobacteria and Bacterioidetes; 2). The remaining branches of the microbial phylogenetic tree range from underrepresented to virtually unknown and are collectively referred to as “microbial dark matter”.

If you want to target those shadowy, ill-defined branches where exotic and underrepresented organisms belong, you go to environments that might harbor them. Towards this end, Christian Rinke and a large coalition of co-authors collected samples from a wide and varied choice of habitats including the South Atlantic tropical gyre, the Homestake Mine in South Dakota, the Great Boiling Spring in Nevada, the sediment at the bottom of the Etoliko Lagoon in Greece and even a bioreactor. Continue reading “The Power of One: Revealing Microbial Dark Matter Using Single-Cell Sequencing”

My Microbiome Made Me Do It

When I was in school I learned that there were two different kinds of bacteria, the nasty ones (pathogens) that could make you sick and the nice ones (commensals), which simply colonized you and did nothing much except occupy a spot that could otherwise be taken up by a pathogen. Any role for those commensal bacteria in health and disease was assumed to be no more than that of a harmless squatter. In recent years, studies of this benign microbial population (microbiome studies) have begun to reveal many more intriguing details about how they affect our health and wellbeing. Maybe it’s not so surprising that “good” bacteria could be good for our health—but could they actually affect how we behave? A review in Science summarized findings that indicate that this is indeed the case—at least for certain animal populations. Could it be true for humans as well? Could our colonizing organisms actually influence how we feel and what we do?

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Targeted Medicine: Using Bacteria as Navigators

Badwater Basin in Death Valley, California
Recently, a new strain of bacteria was isolated from brackish water at the Badwater Basin in Death Valley National Park in California and characterized as a novel species of magnetotactic bacteria (1), a type of bacterium that synthesizes nanocrystals of magnetite (Fe3O4) and greigite (FeS4). These bacteria orient themselves and navigate along geomagnetic fields using intracellular, membrane-bound magnetic nanocrystals, collectively named the magnetosome.

[Yawn] Another bacterial strain in a world where bacteria are one of the most abundant life forms. Ho hum, right? Not so fast! Wait until you see what these bacteria—or more specifically, the magnetosomes—can do. Magnetotactic bacteria might provide us with a great new tool to target delivery of chemotherapeutic drugs, recombinant proteins and medically relevant antibodies, ligands and nucleic acids to treat a wide range of diseases. Continue reading “Targeted Medicine: Using Bacteria as Navigators”

Finding Life on Mars May Be Complicated by Microbes Hitching a Ride from Earth

“The Andromeda Strain”, a novel written by Michael Crichton, remains one of my favorite science fiction novels for two reasons (spoiler alert for the plot): The US government deliberately sent objects into space to scoop up extraterrestrial microorganisms and examine their potential to be used as a weapon (with the expected consequences of contaminated space probes falling near human habitats and causing trouble), and the deadly organism infecting humans is stopped in its tracks by the inescapable bounds of its pH requirements exemplified by two survivors in an afflicted town: a crying baby and a Sterno-drinking man. Reality may be a bit different from the novel but the principle is the same: We are launching probes from our planet and sending them to other planetary bodies, sometimes to stay on another planet, sometimes to return to Earth. In both cases, worries about terrestrial organisms contaminating other planets and extraterrestrial organisms contaminating Earth are valid. Because we are sending more and more probes to examine the possibility of life on other planetary bodies, Curiosity being the most recent example, the question remains: How do you adequately test for organisms that may be hitching a ride from Earth into space? Continue reading “Finding Life on Mars May Be Complicated by Microbes Hitching a Ride from Earth”

Exploiting Bacterial Toxins for Good (Making Lemonade from Lemons?)

Bacterial exotoxins are scary things. The names of the big three: Tetanus, Anthrax and Botulinum, are sufficient to evoke fear and conjure up images of agony, paralysis, mass hysteria, and permanently frozen Hollywood faces. The worst toxin stories are hard to forget. I can still remember the gruesome textbook case studies that accompanied my bacteriology college lectures. There were the home-canning-gone-horribly-awry botulism stories, the historical examples of agonizing tetanus poisonings, and the less lethal but still nasty cases of fast-acting staph toxins delivered to unsuspecting airline passengers in re-heated meals (avoid the ham sandwiches!). It’s all coming flooding back to me.

So, a healthy respect for bacterial toxins is not a bad thing. The worst ones are highly potent and lethal, others may be less potent but are still capable of delivering effects from temporary misery to long-lasting debilitation. But it’s not all bad news. As any microbiology student knows, studies of bacterial toxins have led to some of the most significant advances in the history of medicine–the most well-known example being the development of vaccines based on denatured, inactive forms of toxins. Tetanus and diphtheria are the classic examples where knowledge of the properties of the toxin itself proved to be the key to developing treatment strategies. Continue reading “Exploiting Bacterial Toxins for Good (Making Lemonade from Lemons?)”

Quorum Sensing in Bacteria: How a Picture can be Worth a Thousand Words

Increasingly, multimedia and video are being used in addition to traditional delivery methods to communicate scientific findings. Journals such as PLoS ONE, Cell, Nature and others often use video to either showcase particular articles, or offer authors the opportunity to include multimedia elements as part of their article. Some subjects lend themselves better to video delivery than others. Every so often a video report comes along that perfectly complements the content of the associated paper, illustrating the power of video to enhance communication of research findings.

In my opinion, the effective use of video to highlight results is beautifully illustrated by the report below, highlighting the publication “A synchronized quorum of genetic clocks” by Danino et al, which was published in Nature this week.

[youtube=http://www.youtube.com/watch?v=pnjdAr4EjI0]
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