Finalist SRA 2021: Mathieu – Inhibition of public good production in Salmonella biofilms: An antimicrobial strategy that selects against resistance in vivo?

Mathieu Joos

Bacterial infections pose an increasing danger to human health. However, many people are not aware of this health issue, as combatting bacterial infections with an antibiotic treatment used to be straightforward over the past decades. This is no longer the case since bacteria have found ways to adapt and survive such a treatment. Moreover, bacteria often appear together in dense communities, called biofilms, in which they are enclosed in a protective slime layer, making them even less prone to antibiotics. One pathogen whose antibiotic resistance and biofilms cause many problems is Salmonella, known for the infections caused by eating raw eggs or chicken. Therefore, new ways to treat bacterial infections are being developed to circumvent these issues. A promising strategy are public good inhibitors, targeting costly molecules produced by the individual bacteria that provide a benefit to the bacterial ‘society’. A bacterial public good can be compared to the public goods of our society. For example, everybody in our society pays taxes to contribute to some shared benefits such as a pension fund, education and hospitals. However, some people will evade taxes while still being able to benefit from these public goods, hence indirectly gaining benefits from the taxpayers without contributing themselves. Likewise, in bacterial populations, some cells will be deficient in the public good whilst reaping the benefits. In turn, these cheaters will have more energy left for essential growth processes compared to those who cooperate to the public good production. It is therefore predicted that cheats will outcompete the contributors in the end, hence resulting in collapse of the bacterial society. A similar population collapse could thus be obtained when an infection is treated with a public good inhibitor.

In this thesis, the public good that was studied is the slime layer produced by Salmonella. Inhibiting this slime layer can be a promising strategy to treat salmonellosis as it will render the bacteria more susceptible to the immune system or antibiotic treatment. For this strategy to provide a long term solution that is less prone to resistance development, the benefit and exploitability of the slime layer produced by Salmonella will be evaluated in nematodes. The results obtained in this thesis, however, point to the slime layer not influencing the severity of a Salmonella infection. Subsequently, inhibition of the slime layer also didn’t clearly result in a higher susceptibility against antibiotics. Furthermore, some degree of segregation between the cheaters and contributors of the slime layer was seen in the nematodes, explaining the limited exploitation of the slime layer. Finally, a resistant strain was needed against the anti-slime layer inhibitor to be able to confirm the counterselection of resistance in a population consisting of sensitive cells in a later stage of the research. However, in the time frame provided to complete this thesis, this resistant cell was not obtained.

Wil je Mathieu aan het werk zien? Kom dan naar de finale van de VBI Student Research Awards op 13 oktober in de Aula van de 2e Hoofdwet in Leuven en help haar de hoofdprijs te bemachtigen! Meer info