Evolution toward maximum transport capacity of the Ttg2 ABC system in Pseudomonas aeruginosa
Daniel Yero, Lionel Costenaro, Oscar Conchillo-Solé, Mireia Díaz-Lobo, Adrià Mayo, Mario Ferrer-Navarro, Marta Vilaseca, Isidre Gibert, Xavier Daura
Received Date: 30th October 19
In Pseudomonas aeruginosa, Ttg2D is the soluble periplasmic phospholipid-binding component of an ABC transport system thought to be involved in maintaining the asymmetry of the outer membrane. The crystallographic structure of Ttg2D at 2.5Å resolution reveals that this protein can bind two diacyl phospholipids. Native and denaturing mass spectrometry experiments confirm that Ttg2D binds two phospholipid molecules, which may have different head groups. Analysis of the available structures of Ttg2D orthologs allowed us to classify this protein family as a novel substrate-binding protein fold and to venture the evolutionary events that differentiated the orthologs binding one or two phospholipids. In addition, gene knockout experiments in P. aeruginosa PAO1 and multidrug-resistant strains show that disruption of this system leads to outer membrane permeabilization. This demonstrates the role of this system in low-level intrinsic resistance against certain antibiotics that use a lipid-mediated pathway to permeate through membranes.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.