The plague, caused by the bacterium Yersinia pestis, has been a persistent threat to human populations for centuries. A recent study published in the journal Science sheds light on how a single gene in the bacterium allowed it to adapt and survive for hundreds of years. The research, conducted by scientists at McMaster University and France’s Institut Pasteur, reveals that changes in the copy number of the pla gene led to a reduction in virulence and an increase in the length of time it took to kill its victims.

The study examines the evolution of the plague during three major pandemics: the Plague of Justinian, the Black Death, and the third plague pandemic. The researchers found that strains of the Justinian plague became extinct after 300 years of ravaging European and Middle Eastern populations. Strains of the second pandemic emerged from infected rodent populations, causing the Black Death, before breaking into two major lineages.

One lineage is the ancestor of all present-day strains, while the other re-emerged over centuries in Europe and ultimately went extinct by the early 19th century. The researchers used hundreds of samples from ancient and modern plague victims to screen for the pla gene and perform extensive genetic analysis.

Their findings suggest that a reduction in the copy number of the pla gene led to a decrease in virulence and an increase in the length of time it took to kill its hosts. In mice models of bubonic plague, this change resulted in a 20% reduction in mortality and increased the length of infection, allowing the hosts to live longer before dying.

The scientists also identified a striking similarity between the trajectories of modern and ancient strains, which independently evolved similar reductions in pla in the later stages of the first and second pandemic. This suggests that when the gene copy number dropped, the infected rats lived longer, spreading the infection farther and ensuring the reproductive success of the pathogen.

The researchers propose that this evolutionary change may reflect the changing size and density of rodent and human populations. They also found three contemporary strains with pla depletion in a collection at the Institut Pasteur.

This study provides valuable insights into the evolution of the plague and its impact on human history. It highlights the importance of understanding the complex relationships between pathogens, their hosts, and their environments, as well as the need for continued research into the causes and consequences of pandemics.

The findings also underscore the ongoing threat posed by the plague in regions like Madagascar and the Democratic Republic of Congo, where cases are regularly reported.

Overall, this study sheds new light on the evolution of a single gene that allowed the plague to adapt and survive for centuries. It emphasizes the importance of continued research into the causes and consequences of pandemics and highlights the need for effective strategies to combat infectious diseases that continue to pose significant threats to global health.

The threat of future pandemics has been heightened by the emergence of new influenza viruses. In recent years, researchers from the Helmholtz Centre for Infection Research (HZI) and the Medical Center — University of Freiburg have made significant progress in understanding how these viruses interact with host cells.

Led by Professor Christian Sieben’s team at HZI, scientists have developed a novel method to study the initial contact between influenza viruses and host cells. This breakthrough allows researchers to investigate the complex process of viral entry in unprecedented detail.

The researchers immobilized individual viruses on microscopy glass surfaces and then seeded cells on top. This innovative “upside-down” experimental setup enables scientists to analyze the critical moment when viruses interact with cells but do not enter them, stabilizing the initial cell contact for further investigation.

Using high-resolution and super-resolution microscopy, the team demonstrated that contact between the virus and the cell surface triggers a cascade of cellular reactions. The accumulation of local receptors at the binding site, the recruitment of specific proteins, and the dynamic reorganization of the actin cytoskeleton are just some of the processes observed in this study.

What’s more remarkable is that researchers applied their method not only to an established influenza A model but also to a novel strain found in bats. The H18N11 virus, which targets MHC class II complexes rather than glycans on the cell surface, was shown to cluster specific MHCII molecules upon contact with the cell.

This groundbreaking research has significant implications for understanding alternative receptors used by new and emerging influenza viruses. The findings provide a critical basis for investigating potential pandemic pathogens in a more targeted manner, identifying new targets for antiviral therapies, and ultimately developing effective treatments against future pandemics.

The EU project COMBINE, launched in 2025 and coordinated by Professor Sieben’s team at HZI, aims to investigate the virus entry process of newly emerging viruses. This research has far-reaching implications for understanding and combating infectious diseases, making it a significant contribution to the global fight against pandemics.

“The world is witnessing a breakthrough in influenza management with the discovery that a single oral dose of baloxavir marboxil (baloxavir) can significantly reduce the transmission of influenza within households. This landmark study, published in The New England Journal of Medicine, sheds light on the first robust evidence that an antiviral treatment can curb the spread of influenza to close contacts.

Conducted by a team of international researchers including the LKS Faculty of Medicine at the University of Hong Kong (HKUMed), the CENTERSTONE trial enrolled 1,457 influenza-positive index patients and 2,681 household contacts across 15 countries from 2019 to 2024. The participants were randomly assigned to receive either baloxavir or a placebo within 48 hours of symptom onset.

The primary endpoint was laboratory-confirmed influenza transmission to household contacts by day 5. And the results are nothing short of remarkable.

‘These findings highlight baloxavir’s potential not only to treat influenza but also to reduce its spread within communities,’ said Professor Benjamin Cowling, co-author of the study and Helen and Francis Zimmern Professor in Population Health. ‘This dual effect could transform how we manage seasonal influenza and prepare for future pandemics.’

The study underscores the complementary role of antiviral drugs alongside vaccination, particularly in unvaccinated populations or during pandemics when vaccines may not be immediately available. The discovery opens doors to new possibilities in public health, where a single dose of baloxavir could become an essential tool in managing and containing outbreaks.

This groundbreaking research has far-reaching implications for the way we approach influenza management and pandemic preparedness. It’s a testament to human innovation and our unwavering commitment to protecting global health.”