While it may sometimes take calamitous headlines about a death caused by a drug-resistant infection, societal awareness of the problem of antibiotic resistance seems to be increasing. Fortunately, many of the factors responsible for the deteriorating situation have been identified, such as the ubiquitous use of antibiotics on healthy livestock to encourage rapid animal growth or the inability to create a new class of effective antibiotics. What’s more, the World Health Organization published recently a list of the 12 families of bacteria that are believed to pose the greatest threat to human health. Our founder, Dr. Rita Colwell, even spoke this week at an American Society of Microbiology conference dedicated to the topic of antibiotic resistance mitigation about assessing microbiomes in complex ecosystems. Despite having such well-defined targets and well-informed experts, the solutions remain far from simple.
The near-universal presence of microbes in the environment is illustrated by their endless applications, from foods to perfumes and fuels. However, as the research community has learned, most the microbial universe, about 99 percent, cannot be cultured and studied in a laboratory. This has made it difficult to get a comprehensive grasp of each of the domains of life – bacteria, eukarya, and archaea. However, thanks to advances in genetic sequencing technology, researchers can now take advantage of whole genome sequencing (WGS) and metagenomics, or the study of microbes in their natural environments. As a study published recently in mSphere illustrates, metagenomics will be crucial to avoiding some of the pitfalls of processes like 16S rRNA sequencing.
Cancer immunotherapy, or leveraging the immune system to treat cancer, is a powerful approach to fighting a diverse disease. While only six active immunotherapies have been approved for cancer treatments, hundreds of others are being tested in clinical trials, and for good reason – in some instances, immunotherapy drugs have bolstered patients’ immune systems well enough to drive cancer into remission, with only a few side effects. Unfortunately, one of the limitations of these drugs is the variability of their effectiveness. Despite some remarkable successes, there are just as many patient stories of immunotherapy drugs failing to deliver any therapeutic benefits. Naturally, researchers have been probing both patient populations to understand what factors might be influencing immunotherapy efficacy. Surprisingly, a team of researchers has discovered recently that gut microbiota may be playing a meaningful role in determining patients’ responses to immunotherapy treatments.
It doesn’t beat or expand greatly as we breathe, like the heart or lungs, respectively, so it can be easy to neglect the all-important functions and status of our largest organ – skin. With the responsibility of defending our bodies from foreign organisms, this significant organ has a complicated job. Adding to this biological complexity is the skin microbiome, or the diverse environment of microorganisms that inhabit the skin’s vast and varied surfaces. By exploring the skin microbiome, researchers have discovered bacteria that can naturally produce antibiotics capable of keeping disease-causing germs in check.
Specifically, as published recently in Science Translation Medicine, a team of scientists has identified protective bacteria that secrete two peptides, or short chains of amino acids, that have antimicrobial properties against a potentially harmful species of bacteria found frequently on the skin, known as Staphylococcus aureus. Using the protective bacteria, the team’s research showed that the antimicrobial secretions could target S. aureus without killing other microorganisms - avoiding the key pitfall of other antibiotics. What’s more, through lab and animal tests, the secretions were shown to be able to kill even drug-resistant S. aureus, known as MRSA.
If it were possible to form a circus featuring bacteria, it would give any show a run for its money. With so many remarkable biological characteristics and abilities, bacteria are a constant source of novel research discoveries, one of latest of which was published recently in the journal Chem.
As you may know, there exist what are known as electrogenic bacteria, which live in environments without oxygen, such as sediment in lakes or seas, and produce current as part of their metabolism. These microorganisms can breathe iron and mineral compounds like we breathe oxygen. However, as the Chem publication shares, researchers have discovered a way to enable non-electrogenic bacteria to have the same current-producing abilities.
Another week has come and passed, and delivered more news from the frontlines of microbial warfare. Although, instead of viruses and bacteria doing biological battle, a new publication in Nature Communications details how scientists pitted competing bacterial groups against each other and predicted how the conflict would unfold using previously existing physics equations.
Throughout the course of history, countless rivalries, varying in size, duration, and intensity, have been developed and resolved. But one of the oldest and most intense is the evolutionary-spurred conflict between bacteria and bacteriophages (or phages, which are viruses that target bacteria). Despite the longevity of this biological relationship (and because of it), scientists are continuing to discover the mechanisms bacteria use to defend themselves from phage attacks, and those that have evolved in phages to overcome bacterial defenses. It was in the course of studying this interplay that Dr. Rotem Sorek and his colleagues discovered recently a mechanism by which viruses can communicate.
As many microbiologists can attest, microbiome research is not for the squeamish. From swabbing roadkill carcasses to isolating the DNA present in human waste samples, microbiome researchers aren’t afraid to get dirty – they probably even enjoy it. Yet, it’s hard to imagine that Dr. Nathan H. Lents and his team from John Jay College of Criminal Justice, City University of New York, enjoyed their probing of 21 decomposing cadavers. As part of study published recently in PLOS ONE, Lents and his team collected and analyzed bacteria from the ears and noses of cadavers as the corpses decomposed over the course of weeks.
You may not know that the forensic techniques used currently to identify how long someone has been dead are still not very precise. As such, death investigations, which often include identifying what’s known as the postmortem interval (PMI), or the time that has elapsed since a person has died, provide limited answers to critical questions. That’s what inspired the researchers to analyze the “necrobiome” – the community of microorganisms found on a dead body.
As described in the publication, the research team sampled skin microbiota from the noses and ears of decomposing cadavers to see if they could gain microbiological clues that can eventually be used to help more precisely identify times of death when dead bodies are found. Specifically, the researchers noted the importance of analyzing the cadavers as they decomposed, as it enabled them to take stock of which microorganisms took over the sampled parts of the body, and at what times. They are hopeful that this proof-of-concept study will lead to the realization of reliable microbial indicators that will enable forensics experts to better determine time since death.
It’s also important to note that the team relied on next-generation sequencing and metagenomic analysis of the necrobiome samples to capture the most comprehensive and accurate information for their research. While this study is certainly novel, it joins a growing number of publications that are focused on leveraging metagenomic DNA sequencing and analysis techniques to improve forensic investigations. Bacteria may now often be the culprits, causing deaths through infections, but as this and other studies show, they may soon be helping convict human murderers instead.
For an avid drug discovery spectator, a story about a biologist traveling to the geographic end of the Earth or an environment not yet examined by humans is nothing new. Faced with less effective antibiotics due to overuse, clinicians and drug developers are clamoring to find viable replacements for treatments with waning efficacy, making these adventurous stories more common. But even those who are familiar with zealous drug discovery efforts might be surprised by the research undertaken previously by a team of chemists and microbiologists from the University of Oklahoma: they sought new drug candidate molecules in roadkill.
As discussed in The American Chemical Society’s Journal of Natural Products, the team developed a protocol to find and use “fresh” roadkill on the side of a highway to explore mammalian microbiomes for bacteria that hold properties that could be useful for drugs. The published study focuses specifically on samples collected from the ear of a roadkill opossum but the research left no carcass unturned.
Why roadkill? Well, the team chose to explore roadkill microbiomes because they saw the human microbiome as a crowded research space, leaving other mammalian systems ripe for investigation. Okay, the animal focus makes sense but why dead animals? Here again the researchers made a logical choice - they wanted to avoid the ethical pressures and dilemmas that can arise in live animal testing. So, after jumping circumventing a few regulatory hurdles, including one related to animal carcass possession, the team was clear to start roadside collection of the various roadkill microbiomes.
With plenty of biological samples, the researchers set to work narrowing down the deer, raccoon, skunk, armadillo, squirrel, and opossum microbiomes to bacterial isolates and compounds that had the potential for drug development. They did this vetting using genomic analysis, among other tools and techniques. The most convincing results of their roadkill research turned out to be two bacterial isolates culled from an opossum ear. As the publication explains, these isolates were shown to limit fungal cells’ biofilm formation, making them attractive for potential development.
As microbiome research in humans and other species continues at breakneck speed, stories like this remind us 1) that we can never be too sure about where the next breakthrough in drug development will come from 2) metagenomics and its related tools are increasingly valuable, and 3) the importance of staying curious. This story just may also make it easier for you to bear the emotional burden next time you take the life of a defenseless animal with your fender. Just tell yourself, “it’s for science.”