Friday, January 02, 2026

Why Some Bacteria Survive Antibiotics and How to Stop Them - New study reveals that bacteria can survive antibiotic treatment through two fundamentally different “shutdown modes”

The Hebrew University of Jerusalem

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Disrupted Bacteria
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Credit: Balaban Lab

New study reveals that bacteria can survive antibiotic treatment through two fundamentally different “shutdown modes,” not just the classic idea of dormancy. The researchers show that some cells enter a regulated, protective growth arrest, a controlled dormant state that shields them from antibiotics, while others survive in a disrupted, dysregulated growth arrest, a malfunctioning state marked by vulnerabilities, especially impaired cell membrane stability. This distinction is important because antibiotic persistence is a major cause of treatment failure and relapsing infections even when bacteria are not genetically resistant, and it has remained scientifically confusing for years, with studies reporting conflicting results. By demonstrating that persistence can come from two distinct biological states, the work helps explain those contradictions and provides a practical path forward: different persister types may require different treatment strategies, making it possible to design more effective therapies that prevent infections from coming back.

Antibiotics are supposed to wipe out harmful bacteria. Yet in many stubborn infections, a small number of bacterial cells manage to survive, only to re-emerge later and cause relapse. This phenomenon, known as antibiotic persistence, is a major driver of treatment failure and one reason infections can be so difficult to fully cure.

For years, persistence has largely been blamed on bacteria that shut down and lie dormant, essentially going into a kind of sleep that protects them from antibiotics designed to target active growth. But new research led by PhD student Adi Rotem under the guidance Prof. Nathalie Balaban from Hebrew University reveals that this explanation tells only part of the story.

The study shows that high survival under antibiotics can originate from two fundamentally different growth-arrest states, and they are not just variations of the same “sleeping” behavior. One is a controlled, regulated shutdown, the classic dormancy model. The other is something entirely different: a disrupted, dysregulated arrest, where bacteria survive not by protective calm but by entering a malfunctioning state with distinct vulnerabilities.

“We found that bacteria can survive antibiotics by following two very different paths,” said Prof. Balaban. “Recognizing the difference helps resolve years of conflicting results and points to more effective treatment strategies.”

Two “Survival Modes” and Why They Matter

The researchers identified two archetypes of growth arrest that can both lead to persistence, but for very different reasons:

1) Regulated Growth Arrest: A Protected Dormant State

In this mode, bacteria intentionally slow down and enter a stable, defended condition. These cells are harder to kill because many antibiotics rely on bacterial growth to be effective.

2) Disrupted Growth Arrest: Survival Through Breakdown

In the second mode, bacteria enter a dysregulated and disrupted state. This is not a planned shutdown, but a loss of normal cellular control. These bacteria show a broad impairment in membrane homeostasis, a core function needed to maintain the integrity of the cell.

That weakness could become a key treatment target.

A Framework That Could Transform Antibiotic Strategies

Antibiotic persistence plays a role in recurring infections across a wide range of settings, from chronic urinary tract infections to infections tied to medical implants. Yet despite intense research, scientists have struggled to agree on a single mechanism explaining why persister cells survive. Different experiments have produced conflicting results about what persisters look like and how they behave.

This study offers an explanation: researchers may have been observing different types of growth-arrested bacteria without recognizing they were distinct.

By separating persistence into two different physiological states, the findings suggest a future where treatments could be tailored, targeting dormant persisters one way, and disrupted persisters another.

How the Researchers Saw What Others Missed

The team combined mathematical modeling with several high-resolution experimental tools, including:

Transcriptomics, to measure how bacterial gene expression shifts under stress
Microcalorimetry, to track metabolic changes through tiny heat signals
Microfluidics, allowing scientists to observe single bacterial cells under controlled conditions

Together, these approaches revealed clear biological signatures distinguishing regulated growth arrest from disrupted growth arrest, along with the specific vulnerabilities of the disrupted state.

Cartoon Bacteria

Credit

Balaban Lab

Journal

Science Advances

DOI

10.1126/sciadv.adt6577

Method of Research

Experimental study

Subject of Research

Cells

Article Title

Differentiation between regulated and disrupted growth-arrests allows tailoring of effective treatments for antibiotic persistence

Article Publication Date

2-Jan-2026

First ancient human herpesvirus genomes document their deep history with humans

Genomic data confirm that certain human herpesviruses became part of the human genome thousands of years ago

University of Vienna

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Laboratory technician and one of the authors in the contamination-controlled ancient DNA laboratory at the University of Tartu extracting tiny amounts of DNA from centuries-old skeletons.
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Credit: University of Tartu Institute of Genomics Ancient DNA Laboratory

For the first time, scientists have reconstructed ancient genomes of Human betaherpesvirus 6A and 6B (HHV-6A/B) from archaeological human remains more than two millennia old. The study, led by the University of Vienna and University of Tartu (Estonia) and published in Science Advances, confirms that these viruses have been evolving with and within humans since at least the Iron Age. The findings trace the long history of HHV-6 integration into human chromosomes and suggest that HHV-6A lost this ability early on.

HHV-6B infects about 90 percent of children by the age of two and is best known as the cause of roseola infantum – or "sixth disease" – the leading cause of febrile seizures in young children. Together with its close relative HHV-6A, it belongs to a group of widespread human herpesviruses that typically establish lifelong, latent infections after an initial mild illness in early childhood. What makes them exceptional is their ability to integrate into human chromosomes – a feature that allows the virus to remain dormant and, in rare cases, to be inherited as part of the host's own genome. Such inherited viral copies occur in roughly one percent of people today. While earlier studies had hypothesized that these integrations were ancient, the new data from this study provide the first direct genomic proof.

Recovering viral DNA from the distant past

An international research team led by the University of Vienna and the University of Tartu (Estonia) – in collaboration with the University of Cambridge and University College London – screened nearly 4,000 human skeletal samples from archaeological sites across Europe. Eleven ancient viral genomes were identified and reconstructed – the oldest from a young girl of the Iron Age Italy (1100–600 BCE). The remaining individuals covered a wide geographic and temporal range: Both types of HHV were found in medieval England, Belgium and Estonia, while HHV-6B also appeared in samples from Italy and early historic Russia. Several of the English individuals carried inherited forms of HHV-6B, making them the earliest known carriers of chromosomally integrated human herpesviruses. The Belgian site of Sint-Truiden yielded the largest number of cases, with both viral species circulating within the same population.

"While HHV-6 infects almost 90% of the human population at some point in their life, only around 1% carry the virus, which was inherited from your parents, in all cells of their body. These 1% of cases are what we are most likely to identify using ancient DNA, making the search for viral sequences quite difficult", said the lead researcher of the study, Meriam Guellil, University of Vienna, Department of Evolutionary Anthropology. "Based on our data, the viruses' evolution can now be traced over more than 2,500 years across Europe, using genomes from the 8th-6th century BCE until today."

Ancient integrations, lasting consequences

The recovered genomes allowed the researchers to determine where in the chromosomes the viruses had integrated. Comparisons with modern data revealed that some integrations happened a very long time ago and passed down through generations for millennia. One of the two viral species (HHV-6A) appears to have lost its ability to integrate into human DNA over time – evidence that these viruses have evolved differently while coexisting with their human hosts.

"Carrying a copy of HHV6B in your genome has been linked to angina–heart-disease", says Charlotte Houldcroft (Department of Genetics, University of Cambridge). "We know that these inherited forms of HHV6A and B are more common in the UK today compared to the rest of Europe, and this is the first evidence of ancient carriers from Britain."

A new chapter in virus–host evolution

The discovery of these ancient HHV-6 genomes provides the first time-stamped evidence for the long-term co-evolution of this virus with humans at the genomic level. It also shows how ancient DNA can reveal the long-term evolution of infectious diseases – from short-lived childhood infections to viral sequences that became part of the human genome. Discovered only in the 1980s, HHV-6A and HHV-6B can now be traced back to the Iron Age, offering direct genomic evidence for an ancient, shared history between viruses and humans. "Modern genetic data suggested that HHV-6 may have been evolving with humans since our migration out of Africa," says Guellil. "These ancient genomes now provide first concrete proof of their presence in the deep human past."

Journal

Science Advances

Article Title

Tracing 2500 Years of Human Betaherpesvirus 6A and 6B Diversity Through Ancient DNA

A Coral reef’s daily pulse reshapes microbes in surrounding waters

The Hebrew University of Jerusalem

Dr. Herdís Steinsdóttir deploying an instrument near the reef in Eilat — image:
*Dr. Herdís* Steinsdóttir *deploying an instrument near the reef in Eilat to record water currents, allowing her to keep track of the direction of sea currents.*
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Credit: Photo credit: Jake Stout.

A new study shows that coral reefs don’t just provide a home for ocean life, they also help set the daily “schedule” for tiny microbes living in the water nearby. Over the course of a single day, the quantity and types of microbes present can shift dramatically. To see this in detail, researchers took frequent water samples and used a mix of genetic and ecological methods and tools, as well as advanced imaging techniques, to track what was happening hour by hour. They found that reefs can shape microbial communities through natural interactions like grazing and predation, as well as changes in the reef’s close microbial partners. These daily ups and downs offer a fresh window into how reefs work and influence the surrounding environment— and could even point to new ways to keep an eye on reef health.

Coral reefs are often described as biodiversity hotspots, but new research shows they also act as powerful regulators of the microscopic life in the surrounding ocean. A new study led by Dr. Herdís G. R. Steinsdóttir a postdoctoral researcher under the guidance of Dr. Miguel J. Frada of the Department of Ecology, Evolution and Behaviour at the Hebrew University of Jerusalem and the Interuniversity Institute for Marine Sciences in Eilat and Dr. Derya Akkaynak from the University of Haifa and the Interuniversity Institute for Marine Sciences in Eilat, reveals that coral reefs impose pronounced daily rhythms on nearby microbial communities, reshaping their composition and abundance over the course of a single day.

The study, published in Science Advances, tracked microbial populations in waters above a coral reef in the northern Gulf of Aqaba in the Red Sea, comparing them with nearby open waters across winter and summer seasons. Using high-frequency sampling every six hours, the researchers uncovered previously undocumented daily and seasonal cycles affecting bacteria, microalgae, and microscopic predators.

“We found that the reef is not just passively surrounded by microbes,” said Dr. Frada. “It actively structures microbial life in time, creating daily patterns that repeat across seasons and influence how energy and nutrients move through the ecosystem.”

The research team discovered that reef waters consistently contained significantly fewer bacteria and microalgae than adjacent open waters, suggesting active removal by reef organisms. At the same time, populations of heterotrophic protists, microscopic predators that feed on bacteria, increased sharply at night, sometimes by as much as 80 percent, suggesting predation as a major force shaping microbial dynamics.

One of the most striking findings involved Symbiodiniaceae, the family of dinoflagellates best known as coral symbionts. Genetic signatures of these organisms consistently peaked around midday in reef waters, pointing to daily cycles of release, growth, or turnover that may be linked to light conditions and coral metabolism.

“These daily microbial rhythms were as strong as, and sometimes stronger than, seasonal differences,” said Dr. Steinsdóttir. “This shows that time of day is a critical factor when studying reef-associated microbial communities.”

By combining genetic sequencing, flow cytometry, imaging technologies, and biogeochemical measurements, the interdisciplinary team provides one of the most detailed temporal views to date of microbial life around coral reefs. The findings suggest that microbial daily cycles could serve as sensitive indicators of reef functioning and ecosystem health in a changing ocean.

Dr. Herdís Steinsdóttir deploying an instrument near the reef in Eilat to record water currents, allowing her to keep track of the direction of sea currents.