Inclusion Integrity – Storming the membranous sanctuary of Chlamydia
financed by the Swedish Research Council.
In this project, we aim to investigate how the bacterial pathogen Chlamydia trachomatis maintains the stability of the membranous vacuole within which it resides inside its human host cell. We are also interested in learning how this vacuole can be destabilized, and if we could thereby restrict the growth of the pathogen, for instance as a therapeutic strategy.
The introduction of antibiotics has been one of the greatest achievements in medicine. However, as bacteria develop antibiotic resistance with a fast pace, there is an urgent need for novel treatment strategies.
Many pathogens have the ability to invade human cells and to grow within membrane-enclosed vacuoles in the interior of these cells. One prominent example is Chlamydia trachomatis, a bacterium that causes blinding eye infections and sexually-transmitted diseases.
While human cells have defense systems that can destroy invading microbes or restrict their growth, bacteria that reside in vacuoles are shielded from the host factors that activate these defense programs. We therefore envision that in the future we may fight these microbes by using means that can compromise their ability to maintain these protective vacuoles.
In this project, we aim to investigate how the vacuole of Chlamydia is maintained, how it can be destabilized, and if we can thereby restrict the growth of the pathogen. First, we will identify human and bacterial factors that maintain vacuole integrity. Second, we will reveal how these factors act, in particular by testing our hypothesis that the integrity of the vacuole is determined by its composition, and this in turn by the interactions that take place between the vacuole and the host cell’s own organelles. Third, we will exploit this knowledge to identify drug molecules that can destabilize the vacuoles. And fourth, we will determine how the host cell responds to vacuole damage and how this affects the bacteria.
Overall, I expect that this project will not only advance our understanding of the mechanisms that maintain vacuole integrity, but that it can also pave the way for the development of innovative therapeutic approaches that could in the future act as replacement for broad-spectrum antibiotics and thereby help to reduce the spread of antibiotic resistance.