Phillip E. Klebba, Ph.D., Professor
5 Minutes in LIT
Areas of specialty
- Iron acquisition by active transport through the cell envelopes of bacteria
- Immunological approaches to bacterial pathogenesis
- Biophysical analyses of bacterial membrane transport in living cells
MECHANISMS OF IRON ACQUISITION IN BACTERIAL PATHOGENESIS The thin biological membranes between a cell’s interior and its environment encompass many indispensable functions. Most fundamentally, they create an inward flow of nutrients to supply metabolic precursors for the biochemical pathways that constitute life. But, transport is a selective phenomenon: not all molecules penetrate into cells, because membranes create a permeability barrier that attunes each cell to its individual environment. This acquisition of desirable substances and rejection of undesirable or noxious compounds is a focal point of our research. We are biochemically characterizing active transport processes that internalize compounds against their natural concentration gradients. Electrochemical potential created by ion gradients across membrane bilayers often powers such thermodynamically unfavorable uptake reactions. In these contexts the proteins of bacterial cell membranes sense the environment, identify metabolically beneficial nutrilites, and capture them by membrane transport that involves signal and energy transduction by multicomponent protein assemblies. We are researching one such complex of proteins (TonB-dependent iron transport systems) in Gram-negative cells, and another network of cell envelope proteins (sortase-dependent and independent heme/hemoglobin transporters) in Gram-positive cells. Both systems are potential targets for antibiotic discovery, which is our ultimate goal.
AWARDS, ORGANIZATIONS & PROFESSIONAL SERVICE
Burroughs-Wellcome Scholar, University of California, Los Angeles, 2011-2012
Member, Conseil Scientifique de Fulbright Commission Franco-Americaine, 2002-2003
Chercheur, Institut Nationale de Sante et Researche Medicale (INSERM), Institute Necker, 2002
Fulbright Research Scholar, Franco-American, US State Department, 2002-2003
American Society for Microbiology (ASM) International Professorship (Brasil), 2001
Chercheur de Centre Nationale Researche Scientifique (CNRS), Institute Pasteur, Paris, 1993
Phillipe Foundation International Scholar, 1993, 2002
Evelyn Neizer Post-Doctoral Research Award, Stanford University, 1981
Sigma Xi Research Award, 1975
Smallwood, C., A.M. Gala, A., V. Trinh, S.M.C. Newton & P. E. Klebba. 2009. Fluoresceination of FepA during colicin B killing: effects of temperature, toxin and TonB. Mol. Microbiol. 72:1171-80.
Garimella, R., Hayle, J.L., Harrison, W., Klebba, P.E., Rice, C.V. 2009. Conformation of the phosphate D-alanine zwitterion in bacterial teichoic acid from nuclear magnetic resonance spectroscopy.Biochemistry 48:9242-9
Udho, E., K.S. Jakes, S.K. Buchanan, K. James, X. Jiang, P.E. Klebba & A. Finkelstein. 2009. Reconstitution of Bacterial Outer Membrane TonB-dependent Transporters in Planar Lipid Bilayer Membranes.Proc. Nat. Acad. Sci. USA 106:21990-5.
Newton, SM., V. Trinh, H. Pi and P.E. Klebba. 2010. Direct measurement of the outer membrane stage of ferric enterobactin transport: post-uptake binding.J Biol Chem. 285:17488-97.
Xiao, Q., Jiang, X, Y. Shao, Y., S.M.C. Newton & P.E. Klebba. 2011. Sortase-independent and dependent Systems for Acquisition of Haem and Haemoglobin in Listeria monocytogenes. Mol. Microbiol. 80:1581-97. Epub 2011 May 6.
McLaughlin, H.P., Q. Xiao, R.B. Rhea, H. Pi, P. G. Casey, T. Darby, A. Charbit, R.D. Sleator, S.A. Joyce, R.E. Cowart, C. Hill, P.E. Klebba and C.G.M. Gahan. 2012. A putative P-type ATPase required for virulence and resistance to haem toxicity in Listeria monocytogenes.PLoS One 7:e30928
Klebba, P.E., A. Charbit, Q. Xiao, X. Jiang, and S.M. Newton. 2012. Mechanisms of iron and haem transport by Listeria monocytogenes. Mol Membr Biol. 29:69-86
Dong Li, S.M.C. Newton, P.E. Klebba, C. Mao. 2012. Morphology-controlled synthesis of silica nanotubes through pH- and sequence-responsive morphological change of bacterial flagellar biotemplates.J Mater Chem. 22:15702-15709
Lill, Y., M. Lill, W. Kaserer, S. M. Newton, P.E. Klebba and K.P. Ritchie. 2012. Single-molecule study of molecular mobility in the cytoplasm of Escherichia coli.Physical Review E 86:021907.
Pi., H., S.A. Jones, L.E. Mercer, J.P. Meador, J.E. Caughron, L. Jordan, S.M. Newton, T. Conway & P.E. Klebba, Role of Catecholate Siderophores in Gram-negative Bacterial Colonization of the Mouse Gut.In the press, PLoS One.
Malmirchegini GR, Sjodt M, Shnitkind S, Sawaya MR, Rosinski J, Newton SM, Klebba PE, Clubb RT. 2014 Novel mechanism of hemin capture by Hbp2, the hemoglobin-binding hemophore from Listeria monocytogenes. J Biol Chem. 289:34886-99. PMID: 25315777.
Hanson, M., L.D. Jordan, Y. Shipelskiy, S.M. Newton and P.E. Klebba. 2015. High-throughput screening assay for inhibitors of TonB-dependent iron transport. J. Biomol. Screen. 1087057115613788. PMID: 26518031
Klebba, P.E. 2016. Rotational Surveillance and Energy Transfer Model of TonB Action in Gram-Negative Bacterial Iron Acquisition. J. Bacteriol. 175 (7) PMID: 26787763.
Patel, D.S., Re, S., Wu, E.L., Qi, Y., Klebba, P.E., Widmalm, G., Yeom, M.S., Sugita, S. and Im, W. 2016. Dynamics and Interactions of OmpF and LPS: Influence on Pore Accessibility and Ion Permeability. Biophys J. 110:930-8. PMID: 26910429