1. A noncanonical chaperone interacts with drug efflux pumps during their assembly into bacterial outer membranes
- Author
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Christopher J. Stubenrauch, Rebecca S. Bamert, Jiawei Wang, and Trevor Lithgow
- Subjects
Cell Membranes ,Gene Transfer ,Biochemistry ,Amino Acids ,Biology (General) ,Phylogeny ,Data Management ,Horizontal Gene Transfer ,Organic Compounds ,General Neuroscience ,Escherichia coli Proteins ,Phylogenetic Analysis ,Proteases ,Enzymes ,Phylogenetics ,Chemistry ,Physical Sciences ,Cellular Structures and Organelles ,General Agricultural and Biological Sciences ,Bacterial Outer Membrane Proteins ,Research Article ,Computer and Information Sciences ,Evolutionary Processes ,QH301-705.5 ,Immunoblotting ,Molecular Probe Techniques ,Research and Analysis Methods ,General Biochemistry, Genetics and Molecular Biology ,Drug Resistance, Bacterial ,Escherichia coli ,Genetics ,Sulfur Containing Amino Acids ,Integral Membrane Proteins ,Evolutionary Systematics ,Cysteine ,Molecular Biology Techniques ,Molecular Biology ,Taxonomy ,Evolutionary Biology ,General Immunology and Microbiology ,Organic Chemistry ,Chemical Compounds ,Membrane Transport Proteins ,Biology and Life Sciences ,Membrane Proteins ,Proteins ,Biological Transport ,Cell Biology ,Outer Membrane Proteins ,Bacterial Outer Membrane ,Enzymology ,Molecular Chaperones - Abstract
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., A crosslinking study reveals novel insights into how the chaperone TAM helps Gram-negative bacteria insert the drug efflux pump subunit TolC into their outer membrane. Bioinformatic analyses show that TolC-like proteins can be found in all LPS-containing bacteria, but also in some monodermic Firmicutes.
- Published
- 2022