Research Goal
The research activities of the Group focus on deciphering the structure and function of virulence factors in pathogenic bacteria. To this end, we employ a multidisciplinary approach that includes the use of X-ray crystallography, Cryo-Electron Microscopy, biophysics and biochemistry. Currently, we investigate the mechanism of action of bacterial toxins delivered by the Type 6 Secretion System (T6SS). Nearly a quarter of sequenced Gram-negative bacteria code for the T6SS, which bacteria employ to inject toxins into target cells. The T6SS assembles inside the bacteria. Upon cell contact, this molecular machine is propelled towards the target cell, puncturing their membranes and injecting effector proteins using a contractile spike-like device. Toxins delivered by the T6SS target competing bacteria or eukaryotic host cells, providing a fitness advantage that allows them to thrive and facilitates host colonisation. We hope that our research efforts can provide fundamental scientific advances and inspire the next generation of antimicrobials.
Publications
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Tke5 is a Pseudomonas putida toxin that kills plant pathogens by depolarising membranes
Commun Biol. 2026 Mar 14;9(1):598 DOI: 10.1038/s42003-026-09863-w -
Structural insights into the antibacterial function of the Pseudomonas putida effector Tke5
EMBO J. 2026 Jan 12 doi: 10.1038/s44318-025-00689-6 -
The Pseudomonas aeruginosa Tse4 toxin assembles ion-selective and voltage-sensitive ion channels to couple membrane depolarisation with K+ efflux
PLoS Pathog. 2025 Jun 4;21(6):e1012981. doi: 10.1371/journal.ppat.1012981. PMID: 40465776; PMCID: PMC12169545. -
Electrophysiological dissection of the ion channel activity of the Pseudomonas aeruginosa ionophore protein toxin Tse5
Chem Phys Lipids. 2025 Mar;267:105472. doi: 10.1016/j.chemphyslip.2025.105472. Epub 2025 Jan 6. PMID: 39778700. -
A new class of type VI secretion system effectors can carry two toxic domains and are recognized through the WHIX motif for export
PLoS Biol. 2025 Mar 17;23(3):e3003053. doi: 10.1371/journal.pbio.3003053. PMID: 40096082. -
Selective cargo and membrane recognition by SNX17 regulates its interaction with Retriever
EMBO Rep. 2024 Dec 9. doi: 10.1038/s44319-024-00340-1. Epub ahead of print. PMID: 39653850. -
Tke5 is a novel Pseudomonas putida toxin that depolarises membranes killing plant pathogens
bioRxiv 2025.01.11.632536 doi: 10.1101/2025.01.11.632536 -
Structural and functional insights into the delivery of a bacterial Rhs pore-forming toxin to the membrane.
Nat Commun 14, 7808 (2023). Doi: 10.1038/s41467-023-43585-5 -
The P. aeruginosa effector Tse5 forms membrane pores disrupting the membrane potential of intoxicated bacteria
Article-preprint, Communications Biology (2022), doi: 10.1038/s42003-022-04140 -
Identification of Tse8 as a Type VI secretion system toxin from Pseudomonas aeruginosa that targets the bacterial transamidosome to inhibit protein synthesis in prey cells.
Nat Microbiol 6, 1199–1210 (2021) doi: 10.1038/s41564-021-00950-8 -
Structural insights into Pseudomonas aeruginosaType six secretion system exported effector 8
J Struct Biol. 212(3):107651. (2020) doi: 10.1016/j.jsb.2020.107651. (2020) -
Structural Snapshots of alpha-1,3-Galactosyltransferase with Native Substrates: Insight into the Catalytic Mechanism of Retaining Glycosyltransferases
Angew Chem Int Ed Engl 56, 14853-14857 doi: 10.1002/anie.201707922 (2017) -
Structural basis for selective recognition of acyl chains by the membrane-associated acyltransferase PatA
Nat Commun. 11, 10906. doi: 10.1038/ncomms10906 (2016) -
TssA forms a gp6-like ring attached to the type VI secretion sheath
EMBO J. 35, 1613-27. (2016) -
A Native Ternary Complex Trapped in a Crystal Reveals the Catalytic Mechanism of a Retaining Glycosyltransferase
Angew Chem Int Edit 17:9898-9902 Q1 13/157 (2015)