The ESR Raquel Rodríguez-Alonso just published a paper on how lipoprotein-β-barrel complexes are formed.
The crystal structure of the key BAM component BamA in complex with RcsF was reported.
BamA adopts an inward-open conformation, with the lateral gate to the membrane closed. RcsF is lodged deep within the lumen of the BamA barrel, binding regions proposed to undergo outward and lateral opening during OMP insertion.
On the basis of their structural and biochemical data, the authors proposed a push-and-pull model for RcsF export following conformational cycling of BamA, and provided a mechanistic explanation for how RcsF uses its interaction with BamA to detect envelope stress. Moreover, it was also suggested that the flux of incoming OMP substrates is involved in the control of BAM activity.
More info: https://www.nature.com/articles/s41589-020-0575-0
The ESRs Elisabete Moura and Tiago Baeta just published a paper on how Thanatin impairs the Lipopolysaccharide Transport Complex Assembly by Targeting LptC-LptA interaction.
Thanatin is a naturally occurring antimicrobial peptide reported to cause defects in membrane assembly and demonstrated in vitro to bind to the N-terminal β-strand of LptA. Since this region is involved in both LptA dimerization and interaction with LptC, the mechanism of inhibition of thanatin was studied to discriminate whether its antibacterial effect is exerted by the disruption of the interaction of LptA with itself or with LptC.
For this purpose, the Bacterial Adenylate Cyclase Two-Hybrid (BACTH) system was implemented to probe in vivo the Lpt interactome in the periplasm.
It was found that thanatin targets both LptC–LptA and LptA–LptA interactions, with a greater inhibitory effect on the former. The disruption of LptC–LptA interaction was confirmed in vitro using two different biophysical techniques. In cells treated with thanatin, LptA undergoes degradation and LPS decorated with colanic acid accumulates. These data further support inhibition or disruption of Lpt complex assembly as the main killing mechanism of thanatin against Gram-negative bacteria.
All the info: https://www.frontiersin.org/articles/10.3389/fmicb.2020.00909/full
Carina Matias is the first PhD student of the T2T network to become a doctor in Microbiology.
She has been working in UNION Therapeutics in Denmark for three years and finally defended her thesis "Antibiotic Drug Development" at Danish Technical University, Novo Nordisk Foundation Center for Biosustainability.
It makes us very happy to watch you chase your dreams!
Tomorrow starts the 2019 Annual Meeting of the Train2Target network.
Students and researchers have spent the last hours travelling to Grenoble, in the heart of the French Alps, for another gathering and discussion of the latest results that they've got.
This year, we have as invited speakers Hans-Georg Sahl (U. Bonn), Joen Luirink (VU-NL), André Zapun (IBS), and from our ITN Cuong Vuong (AiCuris) and Paola Sperandeo (UNIMI).
We expect the meeting to be a great success!
Carlos, Arancha, Elisa and Tiago had some posters presented during the meeting.
It was an amazing chance to discuss their research topics with scientists and students from all over the world.
The next Greath Wall Symposium is approaching fast. Between 25 and 27th of September, it will take place in the Pasteur Institute (Paris) one of the biggest gatherings of scientists and researchers in bacterial cell wall topics.
Some ESRs will attend, among these Carlos and Tiago.
For more informations, go to the oficial website of the event: https://thegreatwall-symposium.org/
And don't forget to follow us on our social media platforms for more updates and news.
#Science4All #MSCA #CellWall
The dates are set, flight tickets and hotels booked. The next anual meeting of the Train2Target network will take place in the EPN campus, in Grenoble, between 16 and 18 of October 2019.
Another opportunity to reconnect and network with colleagues, friends and share the recente updates on the ESR's projects.
Follow us on our social media platforms to follow the updates.