Mutual fight against resistant bacteria

Mutual fight against resistant bacteria by Atte Sillanpää @ CSC Online Magazine

The 1st INTEGRATE Summer School was held at the facilities of CSC – IT Center for Science in Espoo, Finland during 7th-10th June 2016. The Summer School is a part of the Marie Curie INTEGRATE ETN project and is funded by the EU Horizon 2020 Programme.

The school was jointly organized by University of Helsinki, University of Eastern Finland, German research organization Fraunhofer IME and CSC. In total the school was attended by 15 ­­­­­doctoral students and postdocs of which altogether 11 students are funded by the INTEGRATE ETN. They were supported by 13 lecturers.

What is INTEGRATE ETN?

Antimicrobial resistance is posing a continuously-rising threat to global health. The INTEGRATE project is a direct response to this. It consists of a consortium committed to training Early Stage Researchers (ESRs) in the discovery and preclinical validation of novel Gram-negative antibacterial agents and targets. The intention is to reverse the fragmentation of approaches towards antibacterial discovery through mutual cooperation.

The INTEGRATE ETN project consists of 11 research groups from all over Europe. A new ESR has been recruited to each research group.

– The target is to together develop new molecules to fight Gram-negative bacteria. The Summer School is a means of knowledge transfer to the ESRs (but also open for other participants), and covers a wide variety of topics that are important for researchers. In addition to drug discovery methods these also include how to write successful grant applications, and how to manage research ethics issues, explains Professor Antti Poso, from the University of Eastern Finland, leading the computer-aided drug design, hit finding, and optimization work package of the project.

 

Professor Antti Poso explains the power use of the MOE Drug Discovery Suite for Elisa Sassetti and Konstantinos Grammatoglou.

 

Where is the Achilles' heel of bacteria?

The coordinator of the project, Professor Gabriele Costantino, University of Parma, Italy, opened the School presenting new directions and new potential targets to keep on fighting multidrug resistant bacteria in what that seems to be a hopeless war.

– Smart approaches, and tight interaction between chemists, microbiologists and clinicians will be the key to success, and INTEGRATE is the optimal environment where a new generation of scientists will be trained to take up the challenge.

One of the participants, Joana Magalhães from Portugal is a chemist designing and synthesising inhibitors of O-acetylserine sulfhydrylase that is one of the enzymes involved in the biosynthesis of cysteine in bacteria. This aligns perfectly with the aim of the project as this is one way of interfering with the development of multidrug resistant phenotypes.

– In other words, this way bacteria can be kept susceptible to existing antibiotics, Magalhães describes.

The Summer School covers a wide area of topics

Magalhães likes the idea of the school exposing the participants to a wide range of technologies like antimicrobial drug discovery, medicinal chemistry and high-throughput screening as well as practical training in molecular modeling and virtual screening which are important for the success of the program.

– The computational part was mostly new to me and learning to use MOE goes immediately into practice at my secondment site in Germany. We also visited FIMM (Institute for Molecular Medicine Finland) and saw a High Throughput Screening setup. We were exposed to different environments from computational tools to biology in order to allow us to develop our personal skills and have ideas for the project, Magalhães reviews the event.

 

Professor Gabriele Costantino presents different strategies to exploit the weak points of Gram-negative bacteria.

 

"Useful and Fun"

Also Elisa Sassetti from the Fraunhofer Institute for Molecular Biology and Applied Ecology IME appreciated the wide coverage of the school. She actually uses both the computational in silico and wet lab methods to overpower E. Coli via inhibiting one of its enzymes.

– The possibility to directly discuss with whole project team and ask advice from the experts of each specific topic was both really useful and fun, summarizes Sassetti.

The INTEGRATE project will continue for almost three more years during which the ESRs will visit several partner sites learning new methods in drug discovery from their local experts. Let's hope we will then have several new ways to protect us from Gram-negative bacteria!

 

 

What is Gram-negativity and resistance to antibiotics?

► Bacteria can be roughly divided into two major groups, gram-positive and gram-negative, according to the structure of their cell membrane. This structure can be easily assessed by a simple staining procedure.

► Gram-negative bacteria include the ubiquitous Escherichia coli but also several bacteria involved in human disease, such as the notorious Yersinia pestis which causes plague.

► Several classes of antibiotics target gram-negative bacteria specifically, so knowing the classification of a bacteria can be helpful when choosing correct medication.

► Bacteria can develop resistance to antibiotics through evolution over time. Typical antibiotics target some essential function in bacteria aiming to turn it harmless. Through mutations the bacteria may change the target function so that the antibiotic is no longer effective. As the antibiotics suppress the multiplication of the non-mutated version of the bacteria, the new drug resistant version will come to dominate.

 

         

Integrate-etn.eu

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska Curie grant agreement No  642620
European Union