How do bacteria adapt when resources run low? ISTA researchers have found that, under starvation stress, E. coli can use bacteriophages and CRISPR-Cas immunity to transfer and incorporate DNA, accelerating genetic reshuffling. The process resembles a primitive form of sexual reproduction and may help bacterial populations adapt to changing conditions. The findings were published in Molecular Biology and Evolution.
Do bacteria have sex? For decades, scientists thought that bacteria reproduced by asexual cell division, known as binary fission, and occasionally took up free DNA or exchanged genetic material "horizontally" from cell to cell. However, evidence suggesting a primitive form of sexual reproduction started to emerge in the 1990s. But how common is this phenomenon?
Now, Pavel Payne and Călin Guet , a postdoc and a professor at the Institute of Science and Technology Austria (ISTA), have uncovered a process resembling sexual reproduction in the gut bacteria Escherichia coli.
"The twist is that the bacteria make use of CRISPR-Cas, a defense system against bacterial viruses that later became the basis for gene-editing technologies," says Guet. "It turns out that bacteria use these viruses to shuttle DNA between themselves. Furthermore, recipient cells can incorporate this DNA into their own genomes and transmit it vertically to their offspring, which is de facto sex."
This DNA transfer process appears to occur when bacteria are close to starvation.
The struggles of sharing genes
The work builds on the discovery of horizontal gene transfer (HGT)—the movement of genetic material between organisms by mechanisms other than vertical inheritance, from parent cell to daughter cell. This phenomenon was described almost a hundred years ago when so-called natural competence was discovered in bacteria. This mechanism is a genetically encoded state that allows bacteria to actively take up free DNA in their environment and integrate it into their genomes. However, far from being a widespread process, only a very small minority of bacteria are naturally capable of doing so. In the 1940s, another form of HGT called "conjugation" was discovered. It enables bacteria to transfer genetic material, including antibiotic-resistance genes, through cell-to-cell contact using a tube-like structure called a sex pilus. A few years later, a third HGT mechanism called "transduction" was discovered. "This is where things got more interesting," says Payne.
A defense system against bacterial viruses?
In one form of transduction, when a virus called a bacteriophage infects a bacterial cell and replicates inside it, it can also accidentally package fragments of bacterial DNA. This DNA can then be transferred to another cell. However, this process cannot sustain frequent DNA exchange in a bacterial population. This is because the vast majority of the newly produced viruses carrying their own genome would ultimately wipe out the susceptible bacterial population. To overcome this challenge, bacteria evolved defense systems such as CRISPR-Cas, targeting the phage genome, thereby gaining protection against subsequent infection by the same phage.
Payne completed his PhD at ISTA in 2016 before returning to the Institute in 2025 as a postdoctoral researcher in the Guet group. During his PhD, he found evidence that the bacterial immune system can lead to herd immunity in bacteria.
"Herd immunity not only protects the bacteria that directly carry the immune system, but also those that don't," he says. "The remaining question was whether the bacteria could use this mechanism to reshuffle their DNA, and if so, how often. If this were to happen, it would have important implications for how the bacteria adapt to changing environments, survive, and evolve."
Using viruses as pollinators in a primitive form of sex
Genetic innovation through mutation alone can be relatively slow. Beneficial mutations generally arise considerably less often than harmful ones and appear in different individuals. DNA exchange can bring these beneficial variants together, thereby accelerating adaptation.
Payne and Guet showed that by using anti-phage immunity as a primitive form of sexual reproduction, the bacteria can adapt and evolve at a much faster rate by reshuffling their DNA.
"Sex is widespread in nature because it can speed up adaptation," says Payne. "In addition, this same mechanism might allow the bacteria to purge deleterious mutations from the population."
By evolving immunity to phages, bacteria not only protect themselves but also enable frequent gene exchange. While they are deadly predators of susceptible cells, the phages become de facto pollinators, carrying bacterial DNA between cells, much like insects carry pollen between flowers. This helps the bacteria reshuffle their genetic information.
Sex during starvation?
The ISTA scientists highlight that although the prevalence of this form of horizontal gene transfer remains quite low in bacterial populations, it still happens at a rate more than 100 times that of spontaneous mutations.
Notably, bacteria reproduce asexually under favorable growth conditions. However, the team observed that this sex-like DNA transfer process occurs when they are close to starvation. In fact, the requirement of a specific gene linked the mechanism to the starvation response.
Taken together, the team showed that phage immunity can make a substantial contribution to genetic variation in bacterial populations, thus greatly increasing its impact on bacterial evolution.
"From an evolutionary perspective, sexual reproduction can be especially advantageous under stressful conditions," says Payne. "Our findings suggest that E. coli can use a comparable DNA reshuffling strategy under starvation stress."
