How Avian Influenza Crosses Species

Avian influenza, commonly known as bird flu, has become an increasingly severe public health issue. According to the CDC, the frequency of avian influenza outbreaks and diversity of virus subtypes have increased significantly in the past decade. In 2022, there were reports of sporadic H5 virus infections in mammals across several U.S. states, Canada, and other countries. Affected animals included fox kits, bobcats, coyote pups, raccoons, skunks, mink, and even seals. Human cases of H5N6 and other subtypes following poultry exposures were reported in China, with several cases resulting in severe or critical illness and death.

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How do Self-Amplifying RNA Vaccines Work?

In late November 2023, regulatory authorities in Japan approved a new SARS-CoV-2 vaccine. Unlike earlier messenger RNA (mRNA) vaccines used to protect against COVID-19, this one relies on a technology called self-amplifying mRNA, or saRNA. Though researchers have long pursued saRNA-based vaccines, this represents the first full approval for the technology in humans and marks an exciting advance in the ongoing development of mRNA vaccines.

Continue reading for an overview of how saRNA vaccines work and some of their advantages relative to standard mRNA vaccines.

A syringe withdraws clear liquid from a sealed glass vial.
 A new type of COVID-19 mRNA vaccine, a self-amplifying RNA vaccine, was recently approved in Japan.
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Cyanobacteria Identified as Cause of Elephant Mass Mortality Event

The largest contiguous population of elephants in Africa lives in the Kavango-Zambezi Trans Frontier Conservation Area (KAZA TFCA) which encompasses parts of Botswana Zimbabwe, Zambia, Angola and Namibia. Within KAZA, nearly 90% of the elephant population is concentrated in Botswana (58%) and Zimbabwe (29%). In June of 2020, over 300 elephants were found dead in Botswana under mysterious circumstances. Less than two months later—in a span of only 27 days—34 more elephant deaths were reported in neighboring Zimbabwe. The news of these mass mortality events was both notable and concerning given the importance of the KAZA elephant metapopulation to species conservation.

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For Frogs, Surviving the Heat Could Come Down to What Is in Their Gut

Amphibians are the most threatened vertebrate class worldwide. Because they lack the ability to regulate their own temperature and moisture levels, climate change is playing a significant role in this growing peril (1). Climate change impacts amphibian survival in several ways. In addition to habitat loss, growing drought conditions make maintaining body moisture levels challenging and warming temperatures restrict activity periods needed for reproduction as well as increasing the risk of heat stress.

Heat tolerance varies by species, and understanding what influences these differences could help predict species survival. The gut microbiota is known to affect a wide range of functions in host animals, and recently studies have begun to investigate its role in host thermal tolerance (2).

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Promega qPCR Grant Series #3: Immunotherapy Researcher, Dr. Sabrina Alves dos Reis 

Professional headshot image of Dr. Sabrina Alves dos Reis, subject of the blog post
Sabrina Alves dos Reis

In our third and final installment of the Promega qPCR Grant Recipient blog series, we highlight Dr. Sabrina Alves dos Reis, a trained immunotherapy researcher. Her work has focused on developing tools for more accessible cancer therapies using CAR-T cells. Here, we explore Dr. Alves dos Reis’ academic and scientific journeys, highlight influential mentorship and foreshadow her plans for the Promega qPCR grant funds. 

Dr. Alves dos Reis’ career began with a strong affinity for biology. As an undergraduate student, she pursued a degree in biological science, where she developed a foundational understanding for designing and developing research projects. As her passion for science heightened, she decided to continue her journey in science, culminating in a PhD at the Fundação Oswaldo Cruz Institute in Rio de Janeiro, Brazil. Her research projects focused on the unexplored territory of adipose tissue as a site for Mycobacterium leprae—or leprosy bacillus—infection. She mentioned that this work piqued her curiosity for improving immunotherapies and laid the foundation for her future in cancer research.  

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Clovibactin: A Revolutionary Antibiotic with No Resistance

Pills

Antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of infections. It’s a leading mortality factor worldwide, but the newly discovered antibiotic, clovibactin, may offer a pivotal solution. It effectively kills drug-resistant bacterial pathogens without detectable resistance—even multidrug-resistant “superbugs.”

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On-site, In-house Environmental Monitoring to Obtain Species-Level Microbial Identification

Loss of life and serious illness from contamination of manufactured products that are consumed as food or used in medical procedures illustrate the need to prevent contamination events rather than merely detect them after the fact.  High-profile news stories have described contamination events in compounding pharmacies (1), food processing and packaging plants (2) and medical device manufacturers (3). Although contamination in manufacturing settings can be physical, chemical, or biological, this article will focus environmental monitoring to determine the quality of a manufacturing facility with respect to microbial contamination.

Scientist in pharmaceutical manufacturing facility  performing environmental monitoring.

To ensure that the products they produce and package are manufactured in a high-quality, contaminant-free environment, many industries are required to establish routine environmental monitoring programs. Samples are collected from all potential sources of contamination in the production environment including air, surfaces, water supplies and people. Routine monitoring is essential to detect trends such as increases in potential pathogens over time or the appearance of new species that have not been seen before so that contamination events can be prevented.

Because environmental monitoring requires identification to the level of the species, most environmental monitoring programs will collect samples and then send them off to a facility to be sequenced for genomic identification of any microbial species. Such genotypic analysis involves DNA sequencing of ribosomal RNA (rRNA) genes to determine the taxonomic classification of bacteria and fungi. In this method, informative sections of the rRNA genes are amplified by PCR; the PCR products sequenced; the sequence is compared to reference libraries; and the results interpreted to make a species-level identification for a given microbial isolate.

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Breathtaking Breakthrough: How Gut Microbial VOCs Are Revealing Biomarkers, One Exhale At A Time

The human microbiome, the bustling cooperative of all the microscopic creatures that naturally colonize in and on our bodies, wields a surprising amount of influence over many of the unseen processes that are critical to our overall health and wellness. Over the course of decades, we have learned that this is particularly true for the microbes that reside in our gastrointestinal tract, collectively known as our gut microbiota.

Our gut microbiota is constantly communicating with our bodies, though our relationship with our gut can feel like trying to have a conversation with someone who only speaks a language we do not know or understand—you can take an educated guess at what they are saying based on their expressions and gestures, but the true message and meaning behind their actions is not always discernable. So while we can feel that someone in our gut is unhappy when we have a tummy ache, the true mechanism behind exactly who is unhappy and why, is not as obviously deduced or understood.

What if there was a tool that could help us more easily interpret the language of our microbiota, giving us the means to both better understand our microbiomes as well as to detect biomarkers of various diseases? Recent studies have shown that such a solution may be (quite literally) right under our noses: our breath.

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Bacterium Disrupts Malaria Parasite Development in Mosquitos

Mosquito photo

Mosquitos are the deadliest animal on earth—not because of the itchy bites they leave behind, but because of the diseases those bites can spread. Of these diseases, malaria, is the most widespread, killing 619,000 people in 2021 (1). Almost half of the world’s population live at risk of malaria (2). In humans, malaria is caused by certain species of single-cell micro-organisms belonging to the genus Plasmodium (3), which are transmitted by anopheline mosquitos.

Controlling malaria has proven challenging. Vaccines have yielded incomplete protection, and insecticides that once were successful at control mosquito populations are becoming less effective as the insects develop resistance. Finally, Plasmodium parasites themselves have developed resistance to leading anti-malaria drugs (2).

A New Weapon In The Fight Against Malaria

Approaches that target the disease-causing Plasmodium organisms—inside the mosquito and before they are transmitted to humans—could provide as effective way forward. In the past, researchers have explored leveraging genetically modified bacterium to kill or inhibit Plasmodium development within their mosquito host. However, using genetically altered bacteria makes wide-spread adoption of these techniques problematic. A recent study published in Science describes the discovery and early investigative results using a naturally occurring bacterial strain that inhibits Plasmodium spread (2). The bacteria, Delftia tsuruhatensis TC1, was isolated from a mosquito population that unexpectedly became resistant to Plasmodium infection (2).

Image courtesy of James Gathany and the CDC

Once the bacterium was identified as the cause of Plasmodium inhibition, the researchers tested how easily the bacteria was to introduce into naïve mosquitos and how effective it was at disrupting infection. To do this, they colonized female mosquitos by feeding them a sugar and bacterium solution and then Plasmodium-infected blood. Bacterial colonization occurred in almost all the mosquitos offered the sugar and bacterium food. Initially, bacterial colonization numbers were low, but they increased 100-fold following the blood meal.

Inhibiting Oocyte Formation Disrupts Cycle of Infection

Investigation into how D. tsuruhatensis inhibits Plasmodium infection showed that it inhibits oocyte formation within the gut, and this inhibition lasts for at least 16 days. Specifically, the inhibition is the result of a secreted compound called harmane, which is a small hydrophobic methylated b-carboline (2). When harmane is secreted in the guts of mosquitos it inhibits Plasmodium parasite development. The researchers further found that feeding harmane alone to mosquitos, or allowing it to be absorbed through direct contact produced the same results, but the inhibitory effects only lasted a few days (2).

No matter how harmane is introduced into the gut (directly or through bacterial colonization), the inhibition of oocyte formation results in a decrease in infectivity. Only one third (33%) of mice bitten by Plasmodium-infected, D. tsuruhatensis-colonized mosquitos become infected. This contrasts sharply with the 100% infection rate seen with mice bitten by non-colonized, Plasmodium-infected mosquitos (2). Further testing the researchers also showed that D. tsuruhatensis is not transferred during feeding, suggesting that that bacterium is unlikely to in introduced into mammals through colonized mosquitos.

To investigate how colonization and infection rates would correlate in a ‘real world’ environment, the researchers used a large (10 × 10 × 5 meter) enclosure that replicated the mosquitos’ natural environment. Once again, the mosquitos were colonized with D. tsuruhatensis through overnight feeding of the sugar and bacterium solution. They found ~75% of the mosquitos were colonized by D. tsuruhatensis in this time period.They also found that larvae reared in water seeded with D. tsuruhatensis experienced 100% colonization. In both scenarios, Plasmodium oocyte development was disrupted just as it had been in the laboratory-raise population (2).

Finally, the researchers found that D. tsuruhatensis colonization doesn’t occur between individuals between parent and offspring. For controlling Plasmodium, this means that inoculation with D. tsuruhatensis would require ongoing maintenance. However, it also decreases the risk of a contaminated strain being amplified uncontrollably if released, making it less risky.

Malaria mitigation and control requires a multipronged effort. Using naturally occurring, symbiotic, microbes such as D. tsuruhatensis is one approach that shows promise. There is still a lot of work to be done before this bacterium could be used outside of a controlled environment, including understanding how the bacterium might interact with other plants and animals from the same ecosystem.

References

  1. WHO World malaria report 2022.  Accessed August 22, 2023
  2. Wei Huang et al. (2023) Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes. Science 381, 533–40.
  3. Website. CDC about Malaria—Biology. Accessed August 22, 2023

Cancer Preventing Vaccines: Unleashing the Potential of Tumor Antigens

It has been more than 100 years since Dr. William B. Coley, known today as the “Father of Immunotherapy,” made the first recorded attempt to mobilize the immune system as a means of treating cancer (9). Decades later, the discovery of T cells and the vital role they play in the immune system set the groundwork for many new immunotherapy treatments, such as those involving monoclonal antibodies, cytokines, CAR T cells, and checkpoint inhibitors.

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