Bacteria aren’t just mindless microbes. New research from the Hebrew University of Jerusalem reveals that single bacterial cells can carry a “memory” of their past environments—passing it down through generations—before eventually forgetting. Using a new technique called Microcolony-seq, scientists uncovered hidden subpopulations inside infections, each with different survival strategies. The finding could explain why antibiotics and vaccines sometimes fail—and may point the way toward more precise treatments.

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Scientists at the Hebrew University of Jerusalem have designed a way to uncover a hidden dimension of bacterial life: the ability of single microbes to “remember” their past environments and pass that memory on to their offspring. The discovery, reported in Cell and led by postdoctoral researcher Dr. Raya Faigenbaum-Romm under the supervision of Prof. Nathalie Q. Balaban, and collaboration with Profs. Ilan Rosenshine and Maskit Bar-Meir, introduces a groundbreaking method called Microcolony-seq that captures microbial memory at the earliest stages of colony growth.

For decades, biologists have known that bacteria—though genetically identical—often behave differently. Some grow fast, some slow; some resist antibiotics while others succumb. But until now, it was unclear which of these differences were fleeting accidents and which represented genuine, heritable states.

“What we found is that even a single bacterium carries a long-lasting memory of where it’s been,” says Dr. Faigenbaum-Romm. “When it divides, its descendants preserve that memory—sometimes for 20 generations or more.”

Microcolonies as a Window Into Memory

The Microcolony-seq method works by isolating tiny colonies that sprout from individual bacteria, analyzing their RNA, genomes, and physical traits. This approach avoids the noise of even recent cutting-edge single-cell RNA sequencing methods, and reveals whether differences between cells are genetic mutations or epigenetically inherited phenotypes.

Using this method, the team uncovered surprising stabilities. Pathogens like Escherichia coli and Staphylococcus aureus were shown to split into stable subpopulations—even within a single infection. Some lineages activated virulence programs that help them cling to host cells, while others switched on genes that favored motility or survival in harsh conditions.

Intriguingly, the study showed that this microbial memory has limits. When bacteria reach “stationary phase”—the point when nutrients are depleted—the memory is erased, effectively resetting the population.

Implications for Medicine

The discovery carries urgent implications for human health. In urinary tract and bloodstream infections, Microcolony-seq revealed co-existing bacterial subgroups with distinct antibiotic resistance or virulence profiles. A conventional clinical test that samples just one colony could easily miss these hidden players—leading to treatments that fail.

Prof. Balaban explains: “An infection is rarely a uniform [U1] population of bacteria. It’s more like a coalition of different players, each with its own strengths. To design therapies that truly work, we need to understand—and target—all of them.”

This may help explain why so many experimental drugs and vaccines against S. aureus infections have stumbled in clinical trials: they targeted only one part of the bacterial population, leaving others untouched.

A New Era for Microbial Research

Beyond immediate medical relevance, Microcolony-seq opens new avenues for exploring microbial life. It provides a systematic way to study how bacteria diversify, hedge their bets, and adapt in real time. Future applications could extend to fungal pathogens, the gut microbiome, and even industrial fermentation.

As Dr. Faigenbaum-Romm notes, “We’ve been treating bacteria as if they’re all the same, but in reality, even a single cell carries a story of its past. Microcolony-seq lets us finally read that story.”

The research paper titled “Uncovering Phenotypic Inheritance from Single-Cells with Microcolony-seq” is now available in Cell and can be accessed at https://doi.org/10.1016/j.cell.2025.08.001 .

Researchers:

Raya Faigenbaum-Romm¹, Noam Yedidi², Orit Gefen¹, Naama Katsowich-Nagar², Lior Aroeti², Irine Ronin¹, Maskit Bar-Meir^3,4, Ilan Rosenshine² and Nathalie Q. Balaban¹

Institutions:

1. The Racah Institute of Physics, Edmond J. Safra Campus, The Hebrew University of Jerusalem
2. Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem
3. Pediatrics and Infectious Diseases Division, Shaare Zedek Medical Center
4. Faculty of Medicine, The Hebrew University

For a century, the Hebrew University of Jerusalem has been a beacon for visionary minds who challenge convention and shape the future. Founded by luminaries like Albert Einstein, who entrusted his intellectual legacy to the university, it is dedicated to advancing knowledge, cultivating leadership, and promoting diversity. Home to over 23,000 students from 90 countries, the Hebrew University drives much of Israel’s civilian scientific research and the commercialization of technologies through Yissum, its tech transfer company. Hebrew University’s groundbreaking contributions have been recognized with major international awards, including nine Nobel Prizes, two Turing Awards, and a Fields Medal. Ranked 88th globally by the Shanghai Ranking (2025), Hebrew University marks a century of excellence in research, education, and innovation. To learn more about the university’s academic programs, research, and achievements, visit the official website at http://new.huji.ac.il/en.