RT Journal Article
SR Electronic
T1 Mechanistic aspects of maltotriose-conjugate translocation to the Gram-negative bacteria cytoplasm
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800242
DO 10.26508/lsa.201800242
VO 2
IS 1
A1 Dumont, Estelle
A1 Vergalli, Julia
A1 Pajovic, Jelena
A1 Bhamidimarri, Satya P
A1 Morante, Koldo
A1 Wang, Jiajun
A1 Lubriks, Dmitrijs
A1 Suna, Edgars
A1 Stavenger, Robert A
A1 Winterhalter, Mathias
A1 Réfrégiers, Matthieu
A1 Pagès, Jean-Marie
YR 2019
UL https://www.life-science-alliance.org/content/2/1/e201800242.abstract
AB Small molecule accumulation in Gram-negative bacteria is a key challenge to discover novel antibiotics, because of their two membranes and efflux pumps expelling toxic molecules. An approach to overcome this challenge is to hijack uptake pathways so that bacterial transporters shuttle the antibiotic to the cytoplasm. Here, we have characterized maltodextrin–fluorophore conjugates that can pass through both the outer and inner membranes mediated by components of the Escherichia coli maltose regulon. Single-channel electrophysiology recording demonstrated that the compounds permeate across the LamB channel leading to accumulation in the periplasm. We have also demonstrated that a maltotriose conjugate distributes into both the periplasm and cytoplasm. In the cytoplasm, the molecule activates the maltose regulon and triggers the expression of maltose binding protein in the periplasmic space indicating that the complete maltose entry pathway is induced. This maltotriose conjugate can (i) reach the periplasmic and cytoplasmic compartments to significant internal concentrations and (ii) auto-induce its own entry pathway via the activation of the maltose regulon, representing an interesting prototype to deliver molecules to the cytoplasm of Gram-negative bacteria.