Athina Eleftheraki defends PhD on how bacteria regulate their own toxins

On 22 May 2026, Athina Eleftheraki defended her thesis “A matter of life or death. Regulation of type I toxin-antitoxin systems in bacteria” at Uppsala University. She is the sixth member of UAC's second cohort to reach this milestone.

The toxins bacteria make must be controlled

Bacteria carry genes encoding their own toxins. Left unchecked, these toxins could kill the cell, or stop the growth temporarily. To prevent this, bacteria produce antitoxins that keep toxin levels in check, a system known as toxin-antitoxin (TA). These molecular switches are tightly regulated, and disrupting that regulation can tip the balance between bacterial survival and death. Understanding how they work has implications for antibiotic susceptibility: TA systems have been linked to bacterial persistence, a state in which bacteria tolerate antibiotics without being genetically resistant to them. Athina's thesis focuses on type I TA systems, where the antitoxin is a small non-coding RNA that silences the toxin at the level of translation.

An RNA switch that controls toxin expression

In Papers I and II, Athina characterised the regulatory mechanism of timP/timR, a type I TA system in Salmonella. The toxin mRNA, unlike most others in its class, is not processed by enzymes into its active form. Instead, the research showed that it switches between two mutually exclusive RNA conformations, one that allows translation and one that does not. The antitoxin RNA preferentially targets the active conformation and destabilizes it, blocking toxin production. Paper II mapped this further, identifying a previously unknown long-range interaction within the mRNA that drives the structural switch. Together, the two papers uncover a new mechanism of translation initiation and a non-canonical route to toxin regulation.

An unexpected role in bacterial-phage conflict

Paper III moved from internal gene expression control, to understanding host-pathogen interactions. Bacteria and its viruses, bacteriophages, are in constant evolutionary conflict. TA systems have been described as part of bacterial defense against phages, typically by triggering cell death before a phage can replicate. Athina's work found something unexpected: one chromosomally encoded type I TA system in E. coli does the opposite. Rather than defending against phage infection, it actively promotes in cooperation with a major bacterial immune system, EcoKI. The finding expands what we know about the functions of TA systems and adds a new layer of complexity to how bacteria and phages interact.

New ground in RNA-mediated regulation

Taken together, Athina's thesis advances our understanding of how bacteria control gene expression at the RNA level, expanding what we know about bacterial survival under stress, including antibiotic treatment. The structural RNA switch she characterized represents one of the few known examples of a pseudoknot structure essential for activating translation initiation in bacteria, and may prove more widespread than currently recognized.

UAC congratulates Athina on a her contributions to fundamental microbiology and RNA biology.