Unveiling the Secrets of TB-Fighting Viruses: A Groundbreaking Study on Phage Interactions with Mycobacteria

Tuberculosis (TB) is a devastating infectious disease that claims over one million lives each year. The rise of antibiotic-resistant Mycobacteria has made it even more crucial to develop new treatments. Recently, scientists at Scripps Research and the University of Pittsburgh have employed advanced imaging techniques to provide unprecedented insights into how a tiny virus called a phage invades Mycobacteria.

The research, published in Cell on April 15, 2025, could pave the way for phage-based treatments against antibiotic-resistant TB. Phages, which have evolved over millions of years to target specific bacteria, may offer an alternative solution to traditional antibiotics. However, the phages that combat Mycobacteria, known as mycobacteriophages, remain poorly understood.

Scripps Research assistant professor Donghyun Raphael Park led a team of researchers in creating atomic-level models of the mycobacteriophage Bxb1. They combined data from single-particle cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), allowing them to visualize frozen biological structures at near-atomic resolution.

The results were surprising: unlike other phages, Bxb1 does not form a channel through the bacterial membrane to inject its DNA. Instead, it uses a completely different genome translocation mechanism. Myobacteria’s thick and unusual cell walls make it difficult for phages to inject their genome, highlighting the need for further research.

Park hopes that detailing the structures of other mycobacteriophages will shed light on what structural elements are most important. By studying these structures, researchers can start to identify the hallmarks of an effective phage and design better treatments. This breakthrough study opens doors to developing phage-based therapies for antibiotic-resistant TB and could save countless lives in the future.

A recent study from researchers at George Washington University has shed new light on the relationship between nasal bacteria and COVID-19 risk. Published in EBioMedicine, the research reveals that certain types of nasal bacteria can affect the levels of key proteins the virus needs to enter human cells, offering a crucial insight into why some people are more vulnerable to COVID-19 than others.

The study analyzed nasal swab samples from over 450 individuals, including those who later tested positive for COVID-19. The researchers found that those who became infected had higher levels of gene expression for two key proteins: ACE2 and TMPRSS2. ACE2 allows the virus to enter nasal cells, while TMPRSS2 helps activate the virus by cleaving its spike protein.

Those with high expression for these proteins were more than three times as likely to test positive for COVID-19, while those with moderate levels had double the risk. Notably, men with higher levels of these proteins were more likely to get infected, indicating that elevated protein levels may present a greater risk for men.

To understand what could impact the expression levels of these viral entry proteins, the researchers turned to the nasal microbiome – the diverse community of bacteria that naturally reside in the nose. They found that certain nasal bacteria may affect the expression levels of ACE2 and TMPRSS2, influencing the respiratory tract’s susceptibility to COVID-19.

The study identified three common nasal bacteria – Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis/nonliquefaciens – that were linked to higher expression levels of ACE2 and TMPRSS2 and increased COVID-19 risk. On the other hand, Dolosigranulum pigrum, another common type of nasal bacteria, was connected to lower levels of these key proteins and may offer some protection against the virus.

The findings offer new potential ways to predict and prevent COVID-19 infection. The study suggests that monitoring ACE2 and TMPRSS2 gene expression could help identify individuals at higher risk for infection. The research also highlights the potential of targeting the nasal microbiome to help prevent viral infections.

“We’re only beginning to understand the complex relationship between the nasal microbiome and our health,” said Cindy Liu, associate professor of environmental and occupational health at the GW Milken Institute School of Public Health. “This study suggests that the bacteria in our nose – and how they interact with the cells and immune system in our nasal cavity – could play an important role in determining our risk for respiratory infections like COVID-19.”

The team plans to explore whether modifying the nasal microbiome, such as through nasal sprays or live biotherapeutics, could reduce the risk of infection – potentially paving the way for new ways to prevent respiratory viral infections in future pandemics.

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Timing is Everything: How Daytime Eating Could Protect You from Heart Risks of Shift Work

A recent study led by researchers at Mass General Brigham suggests that food timing could be a bigger risk factor than sleep timing when it comes to cardiovascular health. The study, published in Nature Communications, found that eating only during the daytime could help people avoid the health risks associated with shift work.

Researchers have long known that working night shifts is linked to serious health risks, including heart problems. However, this new study suggests that food timing may be a key factor in mitigating these risks.

“We wanted to understand what can be done to lower cardiovascular risk factors,” said senior author Frank A.J.L. Scheer, PhD, a professor of Medicine and director of the Medical Chronobiology Program at Brigham and Women’s Hospital. “Our new research suggests that food timing could be that target.”

The study involved 20 healthy young participants who were enrolled in a two-week in-patient study at the Brigham and Women’s Center for Clinical Investigation. They had no access to windows, watches, or electronics that would clue their body clocks into the time.

Participants followed a “constant routine protocol,” which allowed researchers to tease apart the effects of circadian rhythms from those of the environment and behaviors. During this protocol, participants stayed awake for 32 hours in a dimly lit environment, maintaining constant body posture and eating identical snacks every hour.

After that, they participated in simulated night work and were assigned to either eating during the nighttime (as most night workers do) or only during the daytime. Finally, participants followed another constant routine protocol to test the aftereffects of the simulated night work.

The investigators examined the aftereffects of the food timing on participants’ cardiovascular risk factors and how these changed after the simulated night work. Researchers measured various cardiovascular risk factors, including autonomic nervous system markers, plasminogen activator inhibitor-1 (which increases the risk of blood clots), and blood pressure.

Remarkably, these cardiovascular risk factors increased after simulated night work compared to the baseline in the participants who were scheduled to eat during the day and night. However, the risk factors stayed the same in the study participants who only ate during the daytime, even though how much and what they ate was not different between the groups – only when they ate.

Limitations of the study include that the sample size was small, although of a typical size for such highly controlled and intensive randomized controlled trials. Moreover, because the study lasted two weeks, it may not reflect the chronic risks of nighttime versus daytime eating.

A strength is that the study participants’ sleep, eating, light exposure, body posture, and activity schedule were so tightly controlled.
“Our study controlled for every factor that you could imagine that could affect the results, so we can say that it’s the food timing effect that is driving these changes in the cardiovascular risk factors,” said Sarah Chellappa, MD, MPH, PhD, an associate professor at the University of Southampton, and lead author for the paper.

While further research is necessary to show the long-term health effects of daytime versus nighttime eating, Scheer and Chellappa said the results are “promising” and suggest that people could improve their health by adjusting food timing. They add that avoiding or limiting eating during nighttime hours may benefit night workers, those who experience insomnia or sleep-wake disorders, individuals with variable sleep/wake cycles, and people who travel frequently across time zones.