Researchers at the University of São Paulo (USP) have identified 45 new toxins produced by bacteria of the genus Salmonella, which includes species associated with foodborne infections. The study, conducted at the Center for Research in Biology of Bacteria and Bacteriophages (CEPID B3) and published in PLOS Biology, shows that these substances primarily act in competition between microorganisms for space and resources. The findings also suggest that, in the future, these toxins may inspire the development of new antibiotics, support further studies in humans, and enable biotechnological applications.

To investigate the microscopic arsenal used by this pathogen, the team analyzed genetic data from Salmonella and its Type VI Secretion System (T6SS), a spear-like mechanism used by the bacterium to inject effectors—molecules such as toxins that interfere with the functioning of other cells—into the environment or directly into competing microorganisms. The analyses were carried out using computational tools that examined the genetic material of 6,165 samples from 149 different types (serovars) of the subspecies Salmonella enterica. This approach enabled the identification of potential toxins, comparison of sequences across different bacteria, and inference of their functions based on similarities with known proteins.

In total, 128 types of toxins were identified, 45 of which are highly distinct from known toxins or had never been described before. “This result implies that the diversity in the world of bacterial toxins and antitoxins is extremely high, with new varieties emerging or diverging radically from previously known related variants,” explains Robson Francisco de Souza, head of the bioinformatics group at the Laboratory of Protein Structure and Evolution (USP/CEPID B3) and one of the study’s authors.

The identified molecules may act in different ways: some are involved in competition against other bacteria, while others have the potential to affect eukaryotic cells, such as fungi, yeasts, algae, and even mammals. “It is possible that some of them play a direct role in human infections, but to confirm this hypothesis, it would be necessary to determine which lineages carry genes targeting eukaryotes and experimentally assess their effects on cells and infection,” the researcher notes.

This diversity is also reflected in the distribution of the discovered effectors among different Salmonella groups. The study shows that each group has its own unique combination of T6SS-secreted molecules. This suggests that the bacterium selects and maintains specific effectors according to the environmental pressures it faces. “The evolution of these systems and this diversity is driven both by gene recombination, which frequently generates and activates new toxins, and by natural selection, which, in a context of biological conflict, fuels an arms race among bacteria,” Souza explains.

The data also indicate that Salmonella subgroups collected from natural environments tend to carry a greater number of effectors than those isolated from patients, suggesting that toxin diversity increases in contexts with a higher variety of competitors. “As new challenges and adversaries emerge, microorganisms need to develop new tools to gain an advantage in these resource-driven disputes,” he adds.

According to the author, these findings are expected to contribute to a better understanding of bacterial competition strategies and pave the way for new clinical and biotechnological applications. “We may even discover applications that we cannot yet anticipate,” Souza predicts. “We believe this because, for example, some of our previous work has already shown that important proteins in eukaryotes originated from bacterial toxins,” he adds, highlighting the broad potential of these compounds.

Souza emphasizes that the field is far from exhausted. “Bacteria such as Salmonella, Acinetobacter, and other organisms still offer opportunities to understand the role of these toxins in ecological interactions,” he says. “We continue to invest in the development of software and pipelines to automate this type of analysis and expand investigations to new lineages, such as archaea and less-studied bacteria, which represent even greater opportunities for discovery,” he concludes.