Antimicrobial Resistance

Antimicrobial Resistance (AMR) is one of the most important challenges we are facing as a modern society. The lab is primarily interested in understanding how bacterial cells (using Staphylococcus aureus as model) interchange pieces of DNA called mobile genetic elements. These mobile elements are quite significant since they are responsible of AMR and give bacteria the ability to survive in many places including us. Our first goal is to understand at the molecular level how mobile genetic elements express their genes and replicate their DNA. Our second goal is to study phage therapy as an alternative to antibiotics or as coadyuvants.

Gene expression and DNA Replication.

All cellular organisms on this planet have one biological process in common: DNA replication. To do so, the two strands of DNA have to be separated. Some mobile genetic elements also replicate and are good model systems to understand this process. We are interested in studying the initiation of replication which is the process by which the strands of DNA are separated at the very first step generating a specific structure known as replication bubble, and how other proteins are assembled conforming the replisome. Depending on the model system different strategies are followed to initiate replication.

Phage Therapy: using phages to treat bacterial infections.

Bacteriophages or phages are viruses that infect bacteria. Remarkably, they are the most abundant biological entities on the biosphere. There is a debate about if phages (or viruses) are organisms or not. Some people do not consider phages as organisms because phages can not reproduce autonomously. Other people do consider viruses as organisms with a two-stage life cycle: intracellular and extracellular. Phages are composed by a nucleic acid molecule (DNA or RNA) surrounded by a coat of proteins. To reproduce their genetic material as well as to make more proteins, they need to infect a bacterial cell and as a consequence of the phage’s cycle the bacterial cell dies. In order to escape from the phage, bacterial cells evolve and in order to infect bacteria, phages evolve too. This process is known as evolutionary arms race. Therefore, we find in nature some bacteria that are resistant to some phages. Sometimes the phage-bacteria relationship becomes symbiotic in the sense that the phage genome integrates into the bacterial genome, so they benefit from each other.
The AMR (antimicrobial resistance) crisis that we are facing is urging us to develop alternative treatments against bacterial infections. Phage therapy is now of great interest. We are interested in understanding the complex relationship that phages and bacteria might establish as well as in designing phages as biotechnological and therapeutic tools.

Experimental Approach and Facilities

We use a multidisciplinary approach to answer the open biological questions in the field. To do so we take advantage of the fantastic working environment that KBC offers. We use genetic and molecular biology experiments in vivo wich are complemented with biochemistry and structural biology approaches such as cryoEM and X-Ray crystallography. The Umeå Core Facility Electron Microscopy is well equipped with a Titan Krios TEM, Falcon 3 detector, Volta phase plate, autoloader; FEI Talos L120C and JEOL 1230 TEM operated at 120 and 80 kV respectively. The X-Ray Crystallography Platform is very well equipped with in-house X-Ray source X8PROTEUM diffraction system, mosquito robot, etc. We also have Synchrotron’s access secured. Additionally, Umeå University hosts a number of outstanding facilities to support a large variety of scientific approaches: Swedish Metabolomics Centre, The Biochemical Imaging Centre, NMR Core Facility, National Microscopy Infrastructure, Protein Expertise Platform, Proteomics, High Performance Computing Center North, etc.