Area of Interest

Bacterial resistance to biocides and antibiotics is an increasing problem.  Resistance is often conferred by expression of membrane-embedded efflux pumps that can accommodate numerous unrelated drugs.  We have discovered a new family of membrane transporters required for multidrug resistance in Escherichia coli.  This family is called the DedA/Tvp38 family in public databases based upon similarity to E. coli DedA and Yeast Golgi apparatus membrane protein/SNARE Associated Protein Tvp38.  Currently, there are thousands of DedA family genes in the online protein database and they are present in most genomes.  They display no significant amino acid identity to protein families of known function including all known membrane transporter families.   We have shown that members of the DedA family are required for E. coli cell division, growth at elevated temperatures, and maintenance of the membrane protonmotive force and drug resistance. Future studies are aimed at characterizing these and other members of the conserved and widespread DedA family. 

Selected Publications

Kumar S, Tiwari V, Doerrler WT. Cpx-dependent expression of YqjA requires cations at elevated pH. FEMS Microbiology Letters 364 (12) 2017.

Jana B, Cain AK, Doerrler WT, Boinett CJ, Fookes MC, Parkhill J, Guardabassi L. The secondary resistome of multidrug-resistant Klebsiella pneumoniae. Scientific Reports 7; 42483, 2017.

Kumar S, Bradley CL, Mukashyaka P and Doerrler WT. Identification of essential arginine residues of E. coli DedA/Tvp38 family membrane proteins YqjA and YghB. FEMS Microbiology Letters 363 (13), 2016.

Kumar S and Doerrler WTE. coli YqjA, a member of the conserved DedA/Tvp38 membrane protein family, is a putative osmosensing transporter required for growth at alkaline pH. J Bacteriology 197, 2292-2300, 2015.

Kumar S and Doerrler WT.  Members of the conserved Escherichia coli DedA protein family are likely membrane transporters and are required for drug resistance. Antimicrobial Agents and Chemotherapy 58, 923-930, 2014.

Doerrler WT, Sikdar R, Kumar S and Boughner LA. New functions for the ancient DedA membrane protein family. J Bacteriology 195; 3-11, 2013.

Sikdar R, Simmons AR, and Doerrler WT. Multiple envelope stress response pathways are activated in an Escherichia coli strain with mutations in two members of the DedA membrane protein family. J Bacteriology 195; 12-24, 2013.

Boughner LA and Doerrler WT. Multiple Deletions Reveal The Essentiality of The DedA Membrane Protein Family in Escherichia coli. Microbiology 158; 1162-71, 2012.

Six D, Lambert B, Raetz CR, Doerrler WT. Density gradient enrichment of Escherichia coli lpxL mutants. Biochim Biophys Acta 1821; 989-993, 2012.

Liang FT, Xu Q, Sikdar R, Xiao Y, Cox JS, and Doerrler WT. BB0250 of Borrelia burgdorferi is a Conserved and Essential Inner Membrane Protein Required for Cell Division. J Bacteriology 192; 6105-6115, 2010.

Sikdar R and Doerrler WT. Inefficient Tat-Dependent Export of Periplasmic Amidases in an Escherichia coli Strain with Mutations in Two DedA Family Genes. J Bacteriology 192; 807-818, 2010.

Thompkins K, Chattopadhyay B, Xiao Y, Henk MC and Doerrler WT. Temperature Sensitivity and Cell Division Defects in an Escherichia coli strain with mutations in yghB and yqjA, Encoding Related and Conserved Inner Membrane Proteins. J Bacteriology 190; 4489-4500, 2008.

Beck S, Marlow VL, Woodall K, Doerrler WT, James EK, and Ferguson GP. The Sinorhizobium meliloti MsbA2 protein is Essential for the Legume Symbiosis. Microbiology 154; 1258-1270, 2008.

Doerrler WT. Density Gradient Enrichment of Escherichia coli Conditional msbA Mutants. Applied and Environmental Microbiology 73; 7992-7996, 2007.

Doerrler WT. Lipid trafficking to the outer membrane of Gram-negative bacteria. Molecular Microbiology. 60; 542-552, 2006.