Approved Research

Influence of genetic variability on facultative intracellular bacteria recognition and persistence.

Lay summary

Over the next 30 years, antibiotic resistant bacteria are expected to kill ~300 million people and produce damages to the economy as disastrous as the 2008/09 global financial crisis. A possible contributing factor are bacteria that we thought were exclusively extracellular having the capacity to infect and subsequently divide within different human cell. This can represent an important factor in continuance of carriage, chronicity of infection and dissemination within our bodies. To understand and tackle this challenge we need to understand the full picture and, in this context, the view that our defence against bacteria is solely based on a specialized set of immune cells functioning as guardians against threats is an important underestimation as most human cells (of all types) have mechanisms to defend against infection. These defence system are basically the last line of defence, but, albeit their importance, we still don't understand exactly how they are organized, how they constituted and how they react to threats (like bacterial infection). This is specially true in the bacteria that we only recently discovered that have the capacity to infect and divide inside human cells. Unsurprisingly, we also know very little about how the genetic variance in these defence mechanisms relates with disease outcomes, for example how effective an antibiotic treatment regime is, how likely a patient is of having a bacterial infection relapse or how likely it is for a patient to progress to severe illnesses. In this project we aim to understand how the genetic fingerprint of a person, focussing on specific defence mechanisms, influences the outcomes of bacterial infections and to understand if there are specific markers that are responsible for these outcomes. This information will allow us to understand better the interaction between our cells and pathogenic bacteria and consequently design better strategies to treat bacterial infections.