Tuberculosis thrives in the lungs, but when the bacteria causing the disease are expelled into the air, they face a much harsher environment with drastic changes in pH and chemistry. Understanding how these bacteria survive this airborne journey is essential for their persistence, yet little is known about the mechanisms that protect them as they move from one host to another.

Now, MIT researchers and their collaborators have identified a family of genes that are crucial for the bacterium’s survival specifically when exposed to the air, likely offering protection during its transmission.

Previously, many of these genes were thought to be nonessential, as they didn’t appear to affect the bacteria’s role in causing disease when introduced into a host. This new study, however, suggests that these genes are vital for transmission rather than proliferation.

“There is a blind spot in our understanding of airborne transmission, especially regarding how a pathogen survives sudden environmental changes as it circulates in the air,” says Lydia Bourouiba, head of the Fluid Dynamics of Disease Transmission Laboratory, associate professor of civil and environmental engineering, mechanical engineering, and core faculty member at MIT’s Institute for Medical Engineering and Science. “Now, through these genes, we have an insight into the tools tuberculosis uses to protect itself.”

The team’s findings, published this week in Proceedings of the National Academy of Sciences, could lead to new tuberculosis therapies that target both infection and transmission prevention.

“If a drug targeted the products of these genes, it could effectively treat an individual and, even before that person is cured, prevent the infection from spreading,” says Carl Nathan, chair of the Department of Microbiology and Immunology and the R.A. Rees Pritchett Professor of Microbiology at Weill Cornell Medicine.

Nathan and Bourouiba co-senior authored the study, which includes MIT collaborators and Bourouiba’s mentees from the Fluids and Health Network: co-lead author postdoc Xiaoyi Hu, postdoc Eric Shen, and students Robin Jahn and Luc Geurts. The research also involved collaborators from Weill Cornell Medicine, the University of California at San Diego, Rockefeller University, Hackensack Meridian Health, and the University of Washington.

Pathogen’s Perspective

Tuberculosis is a respiratory disease caused by Mycobacterium tuberculosis, a bacterium that predominantly affects the lungs and spreads through droplets released by an infected person, typically when they cough or sneeze. Tuberculosis remains the leading cause of death from infection, except during global viral pandemics.

“In the last century, we’ve seen the 1918 influenza pandemic, the 1981 HIV/AIDS epidemic, and the 2019 SARS-CoV-2 pandemic,” notes Nathan. “Each virus has caused significant loss of life, but after they subsided, we were left with the ‘permanent pandemic’ of tuberculosis.”

Much of the research on tuberculosis focuses on its pathophysiology—how the bacteria infect a host—along with diagnostic and treatment methods. For their new study, Nathan and Bourouiba turned their attention to tuberculosis transmission, specifically exploring how the bacteria defend themselves during airborne transmission.

“This is one of the first efforts to study tuberculosis from an airborne perspective, investigating how the organism survives harsh changes in the environment during transmission,” says Bourouiba.

Critical Defense

At MIT, Bourouiba studies fluid dynamics and how droplet behaviors can spread particles and pathogens. She partnered with Nathan, who investigates tuberculosis and the genes that the bacteria rely on throughout their life cycle.

To explore how tuberculosis survives in the air, the team aimed to replicate the conditions the bacterium encounters during transmission. They first worked to develop a fluid with similar viscosity and droplet sizes to those expelled by a person coughing or sneezing. Bourouiba points out that previous research on tuberculosis relied on liquid solutions that are used to grow the bacteria. However, these liquids differ significantly from the fluids tuberculosis patients expel.

Furthermore, the fluid typically sampled from tuberculosis patients, like sputum for diagnostic tests, is thick and sticky, which makes it inefficient at spreading and forming inhalable droplets. “It’s too gooey to break into inhalable droplets,” Bourouiba explains.

Through her research on fluid and droplet physics, the team determined a more accurate viscosity and droplet size distribution for tuberculosis-laden microdroplets in the air. They also analyzed the composition of droplets by studying infected lung tissue samples. They then created a fluid that mimicked the viscosity, surface tension, and droplet size that would be released into the air when a person exhales.

Next, the team deposited different fluid mixtures onto plates as tiny droplets, measuring how they evaporated and what structures they left behind. They discovered that the new fluid shielded the bacteria at the center of the droplet, unlike traditional fluids where bacteria were more exposed to the air. The realistic fluid also retained more water.

The team then infused the droplets with bacteria carrying genes with various knockdowns to see how the absence of specific genes affected bacterial survival during evaporation.

They evaluated over 4,000 tuberculosis genes and identified a family of genes that became crucial in airborne conditions. Many of these genes are involved in repairing damage to oxidized proteins, such as those exposed to air, while others are responsible for breaking down irreparably damaged proteins.

“What we found is a lengthy list of candidate genes, some more prominently involved than others, that could play a critical role in helping tuberculosis survive during transmission,” Nathan says.

While the experiments cannot fully replicate the bacteria’s biophysical transmission (as droplets fly through the air and evaporate), the team mimicked these conditions by placing plates in a dry chamber to accelerate droplet evaporation, similar to what happens in flight.

Going forward, the researchers are developing platforms to study droplets in flight under various conditions. They plan to further investigate the role of the newly identified genes in more realistic experiments, potentially weakening tuberculosis’s airborne defenses.

“The idea of waiting to diagnose and treat someone with tuberculosis is an inefficient way to stop the pandemic,” Nathan says. “Most individuals who exhale tuberculosis haven’t been diagnosed yet, so we need to interrupt its transmission. Understanding the process is key, and now we have some ideas.”

Researchers at MIT have unveiled an autonomous, programmable computer integrated into elastic fibers that can monitor health conditions and physical activity, offering real-time alerts for potential health risks. The fiber, which is nearly invisible to the wearer, is comfortable, machine washable, and can be embedded in clothing such as shirts or leggings.

Unlike traditional “wearables” that monitor health from a single location, such as the wrist or chest, this fiber-based technology offers a unique advantage. It is woven into fabrics, allowing it to stay in contact with large areas of the body, including those close to vital organs, thus enabling a more comprehensive understanding of human physiology.

The fiber computer incorporates a range of microdevices—sensors, microcontrollers, memory, Bluetooth modules, optical communication, and a battery—into a single elastic fiber. MIT researchers attached four fiber computers to a top and a pair of leggings, with each fiber running along a limb. These computers were programmed to use machine learning to autonomously recognize different exercises, achieving an average accuracy rate of about 70%. Remarkably, when the individual fibers communicated with each other, their collective accuracy increased to nearly 95%.

Yoel Fink, Professor of Materials Science and Engineering at MIT and senior author of the study, shared his vision for the future of this technology: “Our bodies broadcast gigabytes of data through the skin every second in the form of heat, sound, biochemicals, electrical potentials, and light, all of which carry information about our activities, emotions, and health. Unfortunately, most if not all of it gets absorbed and then lost in the clothes we wear. Wouldn’t it be great if we could teach clothes to capture, analyze, store, and communicate this important information in the form of valuable health and activity insights?”

In a real-world test, U.S. Army and Navy service members will wear fiber-computer-equipped base layer shirts during a month-long winter mission to the Arctic. The mission, dubbed Musk Ox II, will cover 1,000 kilometers in temperatures averaging -40°F. These fiber computers will provide valuable health data, helping to ensure the safety of participants in extreme conditions.

“In the not-too-distant future, fiber computers will allow us to run apps and get valuable health care and safety services from simple everyday apparel,” said Fink. “We are excited to see glimpses of this future in the upcoming Arctic mission through our partners in the U.S. Army, Navy, and DARPA.”

This research builds upon more than a decade of work at MIT’s Fibers@MIT lab and was supported by various military and academic institutions. The breakthrough comes from overcoming a major engineering challenge: integrating complex microdevices into a fiber that retains flexibility and durability. The researchers achieved this by using a flexible circuit board design and an advanced thermoplastic elastomer that allows the fibers to stretch more than 60% without breaking.

The fiber computers, which can communicate via Bluetooth to a smartphone or other devices, enable the creation of a textile network within garments. When multiple fibers are embedded in a garment, they form a network that shares data and enhances functionality, as seen in their exercise-recognition model. This breakthrough could revolutionize health monitoring and injury prevention.

As the team looks ahead, their next steps include enhancing the interposer technique to incorporate additional microelectronic devices. The team is also preparing for the Arctic mission, where the fibers will be used to monitor the physiological effects of extreme cold on the human body.

U.S. Army Major Hefner, who will lead the Musk Ox II mission, highlighted the potential of this technology: “One of my main concerns is how to keep my team safe from debilitating cold weather injuries—something conventional systems just don’t provide. These computing fabrics will help us understand the body’s response to extreme cold and ultimately predict and prevent injury.”

Karl Friedl, Senior Research Scientist at the U.S. Army, emphasized the transformative potential of the technology: “Imagine near-term fiber computers in fabrics and apparel that sense and respond to the environment and to the physiological status of the individual, increasing comfort and performance while providing real-time health monitoring and protection.”

A new study conducted by researchers from the University of the Free State (UFS), the National Health Laboratory Service, and the University of Venda has revealed for the first time that common brown locusts can carry pathogenic yeasts, including Candida auris, a fungus capable of causing severe infections in humans, particularly in individuals with weakened immune systems or those seriously ill.

The study, titled South African brown locusts, Locustana pardalina, hosts fluconazole-resistant, Candidozyma (Candida) auris (Clade III), uncovers the presence of the disease-causing yeast C. auris in the digestive tracts of locusts. This discovery highlights the potential for locusts to spread this emerging pathogen. The research began in April 2022, with 20 adult locusts collected during a significant locust outbreak in the semi-arid Eastern Karoo region of the Eastern Cape, which lasted from September 2021 to May 2022. The study is currently under peer review.

According to Prof. Carlien Pohl-Albertyn, National Research Foundation (NRF) SARChI Research Chair in Pathogenic Yeasts, the researchers isolated three strains of C. auris from different locusts, two of which also contained strains of Candida orthopsilosis, another potentially pathogenic yeast. “The fact that we were able to isolate C. auris from 15% of the sampled locusts, using non-selective media and a non-restrictive temperature of 30°C, may indicate that C. auris is abundant in the locusts and that specific selective isolation is not mandatory,” said Prof. Pohl-Albertyn.

The study also found C. auris in both the fore- and hindguts of the locusts. The foregut, responsible for food intake and partial digestion, likely serves as the entry point for the yeast via the locust’s feeding activities. The hindgut confirmed that C. auris can survive digestion and may be excreted back into the environment through faeces.

While C. auris poses a significant risk to individuals with compromised immune systems, Prof. Pohl-Albertyn emphasized that healthy humans are not at great risk. “There is currently no proof that ingestion may be harmful to them,” she explained. However, she warned that the yeast could pose dangers to immunocompromised individuals, even though few people in South Africa are in direct contact with locusts.

One of the C. auris strains studied in-depth showed decreased susceptibility to fluconazole, a common antifungal drug, underscoring the need for new antifungal treatments. “This highlights the urgent need to discover and develop new antifungal drugs,” Prof. Pohl-Albertyn added.

The study also raises concerns about how locusts could potentially spread C. auris to other animals, such as birds, and, in some regions, even humans. “The fact that locusts are a food source for other animals could lead to eventual distribution of the yeast to people,” Prof. Pohl-Albertyn noted. In countries where locusts are consumed by humans, direct transmission could be more likely.

This research contributes to understanding the natural hosts of emerging pathogens and their role in spreading these diseases. Prof. Pohl-Albertyn emphasized the importance of understanding how C. auris emerged as a pathogen in multiple countries and how environmental factors may have shaped its evolution. “This has implications for the prevention of the spread of this specific yeast species, as well as our preparedness for new pathogenic yeasts that may be emerging from the environment,” she concluded.