Microorganisms in the spotlight of Swedish Research Council grants

Johan Larsbrink, Associate Professor, Division of Industrial Biotechnology

Johan Larsbrink is leading a research project which has been awarded a project grant of four million SEK for four years within Natural Sciences and Engineering.

Microbial Degradation of Bark – How, and by Whom?

About the project: In this project we will study microbial degradation of bark from trees in both boreal and tropical forests, to be able to make comparative studies of different bark types and from different biotopes. Our research questions concern where the bark-degrading organisms derive, and our guess is that the species that drive the bark breakdown mainly come from the forest floor.

We will conduct experiments over long time spans, as in our recent work, to understand how or if the degradation differs depending on which species are present.

The funding comes very timely as we have recently recruited several people to work with bark, but more with a focus on developing biochemical valorization methods. Hopefully, we will both gain a much deeper understanding of how bark can be broken down in nature, but also be able to create new products from a very abundant but poorly used renewable resource.

• Read more about Johan Larsbrink’s research group

Michaela Wenzel, Associate Professor, Division of Chemical Biology

Michaela Wenzel received grants for two projects: The consolidator grant within Natural Sciences and Engineering, of 10 MSEK for 5 years, and a project grant for international research collaboration within antimicrobial resistance (JPIAMR) of 3.5 MSEK for 3 years (11.7 MSEK in total for the consortium).

New strategies for breaking intrinsic antibiotic resistance of mycobacteria

About the project: In this grant, we will explore the potential of a new class of antimicrobial peptides that we call MAPPs (mycolic acid-layer permeabilizing peptides) against tuberculosis. These peptides, which we have discovered in the genomes of mycobacteria, have the ability to destroy the outer layer of the mycobacterial cell envelope, the mycolic acid layer. This layer is a major hurdle for antibiotics to reach and kill these pathogens and its inactivation considerably enhances the activity of drugs that would otherwise be inactive.

In the project, we will drive forward the discovery of new MAPPs from mycobacterial genomes using AI tools and characterize their potency and mechanisms of action. We are aiming to develop species-specific MAPPs, which only affect mycobacteria. This could relieve the burden of the often several months long antitubercular treatment on the patients’ microbiome, reducing side effects and increasing patient well-being.

Tuberculosis is the undisputed number one deadliest infectious disease caused by a bacterial pathogen, and the emergence of drug-resistant strains in many countries is severely limiting treatment options. Our project could lead to improved treatment of these infections and ties in well with our previous and ongoing research on the outer membrane of Gram-negative bacteria.

• Read more about the project at CARe’s website: New Research Explores Treatment Strategies for Tuberculosis and Antibiotic Resistance
   

Revitalising the antifungal pipeline with transition metals (RAFT)

About the project: In this collaborative grant, we work together with partners in the UK and Australia to develop new metal compounds with antifungal activity. Covering the drug discovery pipeline from design to in vivo models, we will use machine learning and combinatorial chemistry approaches to design and synthesize thousands of new molecules, test their antifungal activity, toxicity, and in vivo efficacy, and investigate their mechanisms of action.

In my lab, we will perform mode of action studies with a new microscopy-based method, providing both a new method platform for mechanistic antifungal studies and, of course, characterize the mechanisms of the new compounds developed in the project. We are particularly interested in compounds with new mechanisms of action and those with low resistance frequencies, which will be prioritized for in vivo testing.

Compared to antibiotic resistance, resistance to antifungals has attracted much less attention, yet it is a serious problem that needs to be addressed with new methods and approaches. For my group, this grant is particularly exciting as this is the first time for us to delve deeper into antifungal research.

• Read more about Michalea Wenzel’s research group
• Read a news text about Michaela Wenzel’s research: Bacterial defence mechanisms targeted for treatment

Johan Bengtsson-Palme, Assistant Professor, Division of Systems and Synthetic Biology

Johan Bengtsson-Palme is leading a project which has been awarded a project grant within research on antibiotic resistance of 5,5 MSEK for 3 years.

Risks associated with evolution in bacterial communities exposed to antibiotics: interactions patterns, virulence enrichment, ecological consequences and resistance development

About the project: Many antibiotic resistance genes originate from environmental bacteria, where they have been naturally selected for in the absence of human impacts. This project aims to investigate the processes induced by antibiotics in microbial communities in controlled settings in the lab.

In the project, we will use microbial model communities exposed to varying levels of antibiotics and study how this affects the evolution of antibiotic resistance among the bacteria in these communities. We will also test how interactions between the microbes are altered, and how this in turn may make the communities less resilient to competition from bacteria causing diseases in humans.

The project will enhance our understanding of the broader impacts of antibiotics on microbial ecology and evolution, and thereby contribute to better mitigation strategies for antibiotic resistance in the environment, and allowing us to better predict resistance development before it shows up in the clinics. The project ties in well as a complement to the work performed to understand the development of new forms of resistance in ongoing projects in the group, as well as within the Centre for Antibiotic Resistance Research in Gothenburg.

• Read more about Johan Bengtsson-Palme’s research group