Finding new agents and mechanisms that disrupt bacterial biofilms

DISRUPT is a consortium project funded by the JPIAMR 6th transnational call 

We search for new substances that can be applied against the formation of bacterial communities, so-called biofilms. This could prevent many infections with antibiotic-resistant and antibiotic-tolerant pathogens.

Project description

Bacterial infections that are related to biofilms (bacterial communities that form a dense coating on diverse surfaces) are difficult to treat with current antibiotic strategies. All the more so when drug resistant bacteria are involved. We investigate new approaches in order to acquire new tools, targets and agents for understanding and treating biofilm-associated infections in four major antimicrobial resistant pathogens: Staphylococci, Pneumococci, E. coli and Pseudomonas.

This consortium project involving labs in Norway (Norwegian Unversity of Life Sciences), Switzerland (University of Lausanne) and Germany (EMBL, Heidelberg), our project is able to screen for anti-biofilm active substances and construct tools to apply them genome-wide, based on state-of-the-art gene sequencing technologies. Finally, we shed light on how exactly the new substances work.

Background

Biofilm-related infections with drug resistant bacteria are particularly difficult to treat, because the biofilm offers bacteria additional protection against antimicrobials. New strategies and compounds to fight such resilient infections are sorely needed. But the full repertoire of genes and processes that are essential for biofilm formation in different microbes is still unknown.

Aim

We want to identify anti-biofilm active substances and antibodies and construct tools to apply them genome-wide. Furthermore, we aim to characterise the mechanisms of action of these novel anti-biofilm agents.

Relevance 

New tools to inhibit biofilm formation will reduce the risks of infections with resistant bacteria and could make them susceptible to existing antibiotics..

 

January 27 2023

Panwar J, Autour A, Merten CA (2023) Design and consruction of a microfluidics workstation for high-throughput multi-wavelength fluoresence and transmittance activated droplet analysis and sorting. Nat Protocolsdoi: 10.1038/s41596-022-00796-2


December 21 2022

Cacace E, Kim V, Knopp M, Tietgen M, Brauer-Nikonow A, Inecik K, Mateus A, Milanese A, Mårli MT, Mitosch K, Selkrig J, Brochado AR, Kuipers OP, Kjos M, Zeller G, Savitski MM, Göttig S, Huber W, Typas A (2022) High-throughput profiling of drug interactions in Gram-positive bacteria. biorxiv. doi: 10.1101/2022.12.23.521747


October 14 2022

Bravo A, Typas A, Veening JW (2022) 2FAST2Q: a general-purpose sequence search and counting program for FASTQ files. PeerJ. 10:e14041. doi: 10.7717/peerj.14041


March 17 2022

Kranjec C, Morales Angeles D, Mårli MT, Fernandez L, Garcia P, Diep DB, Kjos M (2021) Staphylococcal biofilms: challenges and novel therapeutic perspectives. Antibiotics (Basel). 10(2): 131. doi: 10.3390/antibiotics10020131


January 07 2022

de Bakker V, Liu X, Bravo AM, Veening JW (2022) CRISPRi-seq for genome-wide fitness quantification in bacteria. Nat Protocols. 17(2):252-281. doi: 10.1038/s41596-021-00639-6


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The team

Morten Kjos

Team leader NMBU

Jan-Willem Veening

Team leader Lausanne

Nassos Typas

Team leader EMBL

Christoph Merten

Team leader Lausanne

Maria Victoria Heggenhougen

PhD student NMBU

Vincent de Bakker

PhD student Lausanne

Elisabetta Cacace

PhD student EMBL

Alexis Autour

Postdoc Lausanne

Xue Liu

Postdoc Lausanne

Afonso Bravo

PhD student Lausanne

Alexandra Koumoutsi

Research scientist EMBL

Danae Morales Angeles

Postdoc NMBU

Doran Pauka

Webmaster

Luo Yan Yong

PhD student EMBL
Challenge

Antimicrobial resistance is a growing problem worldwide. Infections caused by for example staphylococci (S. aureus), pneumococci (S. pneumoniae), E. coli and Pseudomonas are nowadays often difficult to treat due to increasing antimicrobial resistance. Infections caused by these pathogens are particularly problematic if they are associated with biofilms, since the biofilm provides extra protection against antimicrobial compounds.

Publications
Project

The aim of the project DISRUPT is to identify new strategies to treat biofilm-associated infections caused by staphylococci, pneumococci, E. coli and Pseudomonas. Targeting and inhibiting bacterial biofilm formation will reduce the chances of infections, and possibly resensitize the bacteria to existing antibiotics. By using state-of-the-art genetic technologies combined with high-throughput screens, the aim is to deliver new anti-biofilm strategies and mechanisms to tackle biofilm-associated infections. Furthermore, the project will generate genetic tools, which will be available for researchers worldwide, working to fight these AMR pathogens.