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M. Stephen Trent

Research Summary:

In order to survive, bacteria must quickly respond to changes in the surrounding environment. We are interested in how diverse environmental stimuli promote changes in conserved microbial structures found on the surface of pathogenic bacteria. Currently, our laboratory focuses on the remodeling of lipopolysaccharides or LPS. LPS, also referred to as endotoxin, is the major surface component of Gram-negative bacteria and represents one of the microbial molecular signals responsible for activation of the host innate immune system. Our goal is to identify and characterize the molecular mechanisms necessary for the remodeling of LPS, and to determine how alteration of LPS contributes to evasion of the innate immune response during infection. Several pathogenic bacteria are under investigation in our laboratory including Vibrio cholerae, Campylobacter jejuni, Helicobacter pylori, Salmonella typhimurium, and pathogenic strains of Escherichia coli. Understanding how bacteria remodel their cell surface is of fundamental importance and may yield new therapeutic strategies for intervention in bacterial infections.


2014 Rubin EJ, O'Brien JP, Ivanov PL, Brodbelt JS, Trent. Identification of a broad family of lipid Alate acyltransferases with non-canonical substrate specificity.  Mol. Micro. In press

2013 Carpenter CD, Cooley BJ, Needham BD, Fisher CR, Trent MS, Gordon V, Payne SM.  The Vps/VacJ (Mla) ABC transporter is required for intercellular spread of Shigella flexneri.  Infection and Immunity.  In press.

2013 Henderson JC, O'Brien JP, Brodbelt JS, Trent MS.  Isolation and chemical characterization of lipid A from the outer membrane of gram-negative bacteria, J. Vis. Exp. 79: e50623.

2013 Rubin EJ, Trent MS.  Colonize, evade, flourish:  How glyco-conjugates promote virulence of Helicobacter pylori. Gut Microbes, In press.

2013 Madsen JA, Xu H, Robinson MR, Horton AP, Shaw JB, Giles DK, Kaoud TS, Dalby KN, Trent MS, Brodbelt JS.  High-throughput database search and large-scale negative polarity liquid chromatogrphay-tandem mass spectrometry with ultraviolet photodissociation for complex proteomic samples.  Molecular & Cellular Proteomics, 9:2604-14.

2013 Pride AP, Herrera CM, Guan Z, Giles DK, Trent MS. The outer surface lipoprotein VolA mediates utilization of exogenous lipids by Vibrio cholerae, Mbio. 14: 5-13.

2013 Needham BD, Trent MS. Fortifying the barrier: the impact of lipid A remodeling on bacterial pathogenesis.  Nature Micro Review. 11: 467-81. 

2013 Gattis SG, Chung HS, Trent MS, Raetz CR.  The origin of 8-amino-3,8-dideoxy-D-manno-octulosonic acid (Kdo8N) in the lipopolysaccharide of Shewanella oneidensis.  J. Biol. Chem. 288: 9215-25.

2013 Hankins JV, Madsen JW, Needham BD, Brodbelt JS and Trent MS.  The outer membrane of Gram-negative bacteria:  Lipid A isolation and characterization. Methods Mol. Biol. 966: 239-58. 

2013 Moreira CG, Herrera CM, Needham BD, Parkera CT, Libby SJ, Fang FC, Trent MS, Sperandio V, Virulence and stress-related periplasmic protein (VisP) in bacterial/host 2 associations, PNAS, 110: 1470-5.

2013 Maue AC, Mohawk KL, Giles DK, Poly F, Ewing CP, Jiao Y, Lee G, Ma Z, Monteiro MA, Hill CL, Ferderber JS, Porter CK, Trent MS, Guerry, P, The polysaccharide capsule of Campylobacter jejuni 81-176 modulates the host immune response, Infection and Immunity, 81: 665-72. 

2012 Gellatly SL, Needham B, Madera L, Trent MS, Hancock RE, The Pseudomonas aeruginosa PhoP-PhoQ two-component regulatory system is induced upon interaction with epithelial cells and controls cytotoxicity and inflammation, Infection and Immunity 80: 3122-31

2012 Needham BD, Carroll S, Giles DK, Georgiou G, Whiteley M, Trent MS, Modulating the Innate Immune Response by Combinatorial Engineering of Endotoxin , PNAS 110: 1464-9

2012 Cullen TW, O'Brien JP, Hendrixson DR, Giles DK, Hobb RI, Thompson SA, Brodbelt JS, Trent MS, EptC of Campylobacter jejuni mediates phenotypes involved in host interactions and virulence, Infection and Immunity, 81: 430-40

2012 Hankins JV, Madsen JW, Giles DK, Brodbelt JS, Trent MS, Amino acid addition to Vibrio cholera LPS establishes a link between surface remodeling in Gram-negative and Gram-positive bacteria., PNAS 109: 8722-7

2012 Cullen TW, Madsen JA, Ivanov PL, Brodbelt JS, Trent MS, Characterization of a unique modification of the flagellar rod protein FlgG by the Campylobacter jejuni lipid A phosphoethanolamine transferase, linking bacterial locomotion and antimicrobial peptide resistance, J. Bio. Chem. 287: 3326-36

2011 Cullen TW, Giles DK, Wolf LN, Ecobichon C, Boneca IG, Trent MS , Helicobacter pylori Versus The Host: Remodeling Of The Bacterial Outer Membrane Is Required For Survival In The Gastric Mucosa , PLoS Pathogens 7: 1-18

2011 Hankins JV, Madsen JA, Giles DK, Childers BM, Klose KE, Brodbelt JS, Trent, MS, Elucidation of a novel Vibrio cholerae lipid A secondary hydroxy-acyltransferase and its role in innate immune recognition, Mol Microbiol 81: 1313-29

2011 Madsen JA, Cullen TW, Trent MS, Brodbelt JS, IR and UV Photodissociation as Analytical Tools for Charaacterizing Lipid A Structures, Anal Chem 83: 5107-13

2011 Arroyo LA, Herrera CM, Fernandez L, Hankins JV, Trent MS, Hancock RE, The pmrCAB operon mediates polymyxin resistance in Acinetobacter baumannii ATCC 17878 and clinical isolates through phosphoethanolamine modification of lipid A, Antimicrob Agents Chemother 55: 3743-51

2011 Giles DK, Hankins JV, Guan Z, Trent MS, Remodeling of Vibrio cholerae membranes by incorporation of exogenous fatty acids from host and acquatic environments, Mol Microbiol 79: 716-28

2010 Stead CM, Zhao J, Raetz CRH, Trent MS, Removal of the outer Kdo from Heliobacter pylori lipopolysaccharide and its impact on the bacterial surface , Mol Microbiol 78: 837-52

2010 Herrera CM, Hankins JV, Trent MS, Activation of PmrA inhibits LpxT-dependent phosphorylation of lipid A promoting resistance to antimicrobial peptides, Mol Microbiol 76: 1444-60

2010 Cullen TW, Trent MS, A link between the assembly of flagella and lipooligosaccharide of the Gram-negative bacterium Campylobacter jejuni, PNAS. 107: 5160-5

2009 Rutten, L., Mannie, J.-P. B. A., Stead, C. M., Raetz, C. R. H., Reynolds, C. M., Bonvin, A. M. J. J., Tommassen, J., Egmond, M. R., Trent, M. S.*, and Grois, P*. *Joint Corresponding Authors, Active site architecture and catalytic mechanism of the lipid A deacylase LpxR of Salmonella typhimurium, PNAS. 106: 1960-4

2009 Hankins, J. V. and Trent, M. S., Phosphorylation of Kdo is required for secondary acylation of the V. cholerae lipopolysaccharide, J. Bio. Chem. 284: 25804-12

2008 Kline, T., Trent, M. S., Stead, C. M., Lee, M. S., Sousa, M. C., Felise, H. B., Nguyen, H. V., and Miller, S. I., Synthesis of and Evaluation of Lipid A Modification by 4-Substituted 4-Deoxy Arabinose Anaolgs as Potential Inhibitors of Bacterial Polymyxin Resistance, Biorg. & Med. Chem. Letters 18: 1507-10

2008 Touze, T., Tran, A. X., Hankins, J. V., Mengin-Lecreulx, D. and Trent, M. S., Periplasmic phosphorylation of lipid A is linked to the synthesis of undecaprenyl phosphate, Mol. Micro. 67: 264-277
2008 Tran, A. X., Trent, M. S., and Whitfield C., The LptA protein of Escherichia coli is a periplasmic lipid A binding protein involved in the lipopolysaccharide export pathway, J. Biol. Chem. 283: 20342-9

2008 Stead, C. M., Beasley, A., Cotter, R. J., and Trent, M. S., Deciphering the unusual acylation pattern of Helicobacter pylori lipid A, J. Bacteriology 190: 7012-21

2007 Raetz, C. R. H., Reynolds, C. M. Trent, M. S. and Bishop, R. E., Lipid A modification systems of Gram-negative bacteria, Annual Rev. of Biochem. 76: 295-329

2006 Ernst, R. K., Adams, K. N., Moskowitz, S. M., Kawasaki, K., Stead, C. M., Trent, M. S. and Miller, S. I., The Pseudomonas aeruginosa Deacylase (PagL) required for synthesis of cystic fibrosis-specific lipid A, J. Bacteriology 188: 191-201

2006 Trent, M. S., Stead, C. M., Tran, A. X., and Hankins, J. V. , Diversity of Endotoxin and its Impact on Pathogenesis, J. of Endotoxin Res. 12: 205-223

2006 Tran, A. X., Whittimore, J. D., Wyrick, P. B., McGrath, S. C., Cotter, R. J. and Trent, M. S., The Lipid A 1-Phosphatase of Helicobacter pylori is Required for Antimicrobial Peptide Resistance, J. Bacteriology 188: 4531-4541
2006 Trent, M. S., Stead, C. M., Tran, A. X., and Hankins, J. V, Diversity of Endotoxin and its Impact on Pathogenesis, J. of Endotoxin Res. 12: 205-223

2006 Tran, A. X., Whittimore, J. D., Wyrick, P. B., McGrath, S. C., Cotter, R. J. and Trent, M. S. , The Lipid A 1-Phosphatase of Helicobacter pylori is Required for Antimicrobial Peptide Resistance, J. Bacteriology 188: 4531-4541

2006 Reynolds, C. M., Ribeiro, A. A., McGrath, S. C., Cotter, R. J., Raetz, C. R. H., and Trent, M. S. , An outer membrane enzyme in Salmonella typhimurium that removes the 3´-acyloxyacyl moiety of lipid A, J. Biol. Chem. 281: 21974-87

2005 Tran, A. X., Stead, C. M., and Trent, M. S., Remodeling of Helicobacter pylori lipopolysaccharides, J. of Endotoxin Res. 11: 161-6

2005 Tran, A. X., Lester, M. E., Stead, C. M., Raetz, C. R. H., Maskell, D. J., McGrath, S. C., Cotter, R. J., and Trent, M. S., Resistance to the antimicrobial peptide polymyxin requires secondary myristoylation of Gram-negative bacterial lipid A, J. Biol. Chem. 280: 28186-94

2005 Stead, C. M., Tran, A. X., Ferguson D. A. Jr., McGrath, S. C., Cotter, R. J. and Trent, M. S., A Novel Kdo-Hydrolase that removes the outer Kdo sugar from Helicobacter pylori lipopolysaccharide, J. Bacteriology 187: 3374-83

2004 Trent, M. S, Biosynthesis, Transport, and Modification of Lipid A, Biochemistry and Cell Biology 82: 71-86

2004 Tran, A. X., Karbarz, M. J., Wang, X., Raetz, C. R., McGrath, S. C., Cotter, R. J. and Trent M. S. , Periplasmic Cleavage and Modification of the 1-Phosphate Group of Helicobacter pylori Lipid A, J. Biol. Chem. 279: 55780-91