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.
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