SABDII

Staphylococcus aureus biofilm dynamics and innate immunity

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 Obiettivo del progetto (Objective)

'During my postdoc at a marine biotechnology lab in Newcastle I experienced that bacteria growing in shakeflasks in the lab and bacteria in natural biofilms behave very differently. For instance, the global gene expression and production of secreted proteins is very different between these modes of growth. I would like to bring the knowledge and skills acquired there to a higher level by studying the interaction between a clinically relevant biofilm and host organism. To achieve this, I will study the dynamics of Staphylococcus aureus biofilms in interaction with the human innate immune system in the laboratory of Prof. van Strijp in Utrecht. S. aureus is a Gram-positive coccus that causes life threatening diseases and has become resistant against most antibiotics (MRSA). Our innate immune system is crucial in fighting S. aureus infections. Strikingly, S. aureus evades this defence line by production of small secreted proteins that repress this immune system. In many infections, S. aureus’ growth mode is generally considered to be biofilm-like. Using a novel, biofilm centred approach I will study the interaction between the innate immune system and S. aureus. By comparing planktonic growth with several biofilm stages using proteomic analysis, I will screen for novel immune evasion molecules that are expressed specifically during the biofilm mode of growth of S. aureus. The identified proteins will be studied further using deletion mutants in S. aureus and the proteins will be overexpressed in heterologous hosts, such as E. coli or B. subtilis. Using the mutant strains and the overproduced proteins, the specific interactions of these novel proteins with the innate immune system will be examined, both in vitro and in vivo. The identified molecules will be highly interesting drug targets against a problematic microbial pathogen'

Introduzione (Teaser)

Depending on the conditions, bacteria exhibit a multimodal growth pattern. European scientists investigated how bacterial growth shapes their interaction with the host immune system.

Descrizione progetto (Article)

Staphylococcus aureus is a pathogen capable of causing life-threatening diseases. Its emerging resistance against most antibiotics, particularly the methycillin-resistant strain called MRSA, has made it imperative to determine the mechanism of host invasion and disease persistence.

Our innate immune system helps fight S. aureus infections. However, S. aureus evades this line of defence by producing small secreted proteins capable of repressing the immune system. Given that in many infections, S. aureus grows in biofilm communities, the EU-funded 'Staphylococcus aureus biofilm dynamics and innate immunity' (SABDII) project set out to identify molecules that are expressed specifically during the biofilm mode of growth of S. aureus.

To this end, researchers set up and studied several in vitro biofilm growth models. Apart from characterising the individual stages of biofilm growth, they measured the expression and secretion of immune evasion and immune stimulating molecules. Interestingly, they identified a group of peptides, the S.aureus phenol soluble modulins (PSMs) whose action was highly dependent on their concentration. At low concentrations they stimulated the immune system whereas at high levels they induced immune cell lysis.

These findings were further supported by the generation of deletion mutants in S. aureus as well as overexpression experiments. These tools enabled the SABDII team to study the specific interactions of these novel proteins with the innate immune system.

The identified molecules have the potential to serve as drug targets against S. aureus. Given the increase of MRSA incidences across Europe, these targets could be the solution against this problematic nosocomial pathogen.