Open AccessA noncanonical chaperone interacts with drug efflux pumps during their assembly into bacterial outer membranes
Author(s) -
Christopher J. Stubenrauch,
Rebecca S. Bamert,
Jiawei Wang,
Trevor Lithgow
Publication year - 2022
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001523
Subject(s) - efflux , biology , protein subunit , bacterial outer membrane , inner membrane , transport protein , membrane protein , membrane transport protein , microbiology and biotechnology , chaperone (clinical) , biochemistry , membrane , escherichia coli , gene , medicine , pathology
Bacteria have membrane-spanning efflux pumps to secrete toxic compounds ranging from heavy metal ions to organic chemicals, including antibiotic drugs. The overall architecture of these efflux pumps is highly conserved: with an inner membrane energy-transducing subunit coupled via an adaptor protein to an outer membrane conduit subunit that enables toxic compounds to be expelled into the environment. Here, we map the distribution of efflux pumps across bacterial lineages to show these proteins are more widespread than previously recognised. Complex phylogenetics support the concept that gene cassettes encoding the subunits for these pumps are commonly acquired by horizontal gene transfer. Using TolC as a model protein, we demonstrate that assembly of conduit subunits into the outer membrane uses the chaperone TAM to physically organise the membrane-embedded staves of the conduit subunit of the efflux pump. The characteristics of this assembly pathway have impact for the acquisition of efflux pumps across bacterial species and for the development of new antimicrobial compounds that inhibit efflux pump function.