Scientists discover new mechanism responsible for the spread of Salmonella infections

^{Translation by Diana Taborda}

An international study led by researchers from the University of Coimbra (UC) has discovered a new infection mechanism specific to Salmonella. This mechanism could be important for the development of new therapeutic approaches to stop infections caused by this bacterium.

Salmonella infections occur after consumption of contaminated food and primarily affect the digestive tract. Infected people can develop nausea, cramps, diarrhoea, fever and vomiting.

The research, carried out in collaboration with the Universities of Würzburg (Germany) and Cordoba (Spain) and the Institutes of Mathematical Sciences and Homi Bhabha (India), has just been published in the journal Nature Communications.

In general, when infected by viruses or bacteria, cells in the human body communicate with healthy neighbouring cells to organise a response against the infection. In this study, the researchers show the opposite effect: Salmonella-infected cells release proteins that facilitate the infection of neighbouring cells. Therefore, it was necessary to evaluate and identify "key molecules" involved in the infection and spread process to better understand where to act to prevent infection.

They specifically identified a protein, E2F1, which is decreased during Salmonella infection, both in host cells infected with the bacteria and in neighbouring cells. The decrease in E2F1 protein leads to the disruption of molecules involved in controlling the bacterial-host interaction, in particular microRNAs (small non-coding RNA sequences), which in turn promotes bacterial proliferation in the infected cells.

The research team also found that the initially infected cells release molecules into the extracellular space (outside the cells), in particular the protein HMGB1, which activates neighbouring cells, making them more vulnerable to Salmonella infection. According to the leader of the study, Ana Eulálio, researcher at the Centre for Neurosciences and Cell Biology of the University of Coimbra (CNC) and Professor at the Faculty of Sciences and Technology of the University of Coimbra (FCTUC), "this is a new mechanism that increases our knowledge of the complex interactions established between our cells and microorganisms, in this case the Salmonella bacterium".

The great novelty of this work, she explains, is that "contrary to the existing paradigm, we have discovered that Salmonella not only manipulates infected human cells, but also modifies non-infected neighbouring cells to increase their susceptibility to infection, thus facilitating the spread of the bacteria".

The published results were obtained through studies in cells and animal models, using bioinformatics and cellular and molecular biology tools. These data could play a crucial role in preventing the progression of infection by this bacterium. Miguel Mano, researcher at CNC and professor at FCTUC, and author of the study, explains that "knowing the molecular mechanisms studied by Salmonella may allow the development of therapeutic strategies capable of blocking the spread of the infection".

Read the full scientific paper here.