William T. Doerrler

Area of Interest

Bacterial resistance to biocides and antibiotics is an increasing problem. Often, antibiotic resistance is conferred by expression of membrane-embedded efflux pumps that can accommodate numerous unrelated drugs. We study a family of membrane transporters required for antibiotic resistance in numerous bacterial species. 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, including that of humans. We have shown that members of the DedA family are required for cell division and drug resistance in E. coli and for resistance to the last resort antibiotic colistin in species of Burkholderia and Klebsiella. Future studies are aimed at characterizing these and other members of the conserved and widespread DedA family.

Selected Publications

COMPLETE LIST OF PUBLICATIONS TEXT

• Vijay Tiwari, Amit Sharma, Reygan Braga, Emily Garcia, Ridhwana Appiah, Renee Fleeman, Basel H. Abuaita, Marianna Patrauchan and William T. Doerrler. Klebsiella pneumoniae DedA family proteins have redundant roles in divalent cation homeostasis and resistance to phagocytosis. Microbiology Spectrum 2024 Feb 6;12(2):e0380723. doi: 10.1128/spectrum.03807-23
• Asif Iqbal, George Nwokocha, Vijay Tiwari, Inderjit K. Barphagha, Anne Grove, Jong Hyun Ham, William T. Doerrler. A membrane protein of the rice pathogen Burkholderia glumae required for oxalic acid secretion and quorum sensing. Molecular Plant Pathology; 2023 July 10.
• Molecular Plant Pathology Highlight blog- Newly discovered protein helps a rice pathogen avoid alkaline toxicity
• Tiwari V, Panta PR, Billiot CE, Douglass MV, Herrera CM, Trent MS, and William T. Doerrler. A Klebsiella pneumoniae DedA family membrane protein is required for colistin resistance and for virulence in wax moth larvae. Scientific Reports; 2021 Dec 21;11(1):24365. doi: 10.1038/s41598-021-03834-3.
• Iqbal A, Panta PR, Ontoy J, Bruno J, Ham JH and William T. Doerrler. Chemical or genetic alteration of proton motive force results in loss of virulence of Burkholderia glumae, the cause of rice bacterial panicle blight. Applied and Environmental Microbiology. 2021 Aug 26;87(18):e0091521.
• Panta PR and Doerrler WT. A link between pH homeostasis and colistin resistance in bacteria. Scientific Reports; 2021 Jun 24;11(1):13230.
• Panta PR and Doerrler WT. A Burkholderia thailandensis DedA family membrane protein is required for proton motive force dependent lipid A modification. Frontiers in Microbiology, 12 January, 2021.
• Pradip R. Panta, Sujeet Kumar, Caroline F. Stafford, Caitlin E. Billiot, Martin V. Douglass, Carmen M. Herrera, M. Stephen Trent, and William T. Doerrler, A DedA family membrane protein is required for Burkholderia thailandensis colistin resistance. Frontiers in Microbiology, 05 Nov 2019
• 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 WT. E. 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.