Howard Goldfine, Ph.D.

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Emeritus Professor of Microbiology
Department: Microbiology
Graduate Group Affiliations

Contact information
Department of Microbiology
School of Medicine
203D Johnson Pavilion
Philadelpha, PA 19104
Office: 215-898-6384
Fax: 215 898-9557
Education:
B.S. (Biology/Chemistry)
City College of New York, 1953.
Ph.D. (Biochemistry)
University of Chicago, 1957.
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Description of Research Expertise

Research Interests
The structures, functions and formation of bacterial membrane lipids

Key words: phospholipids, plasmalogens, anaerobic bacteria, Clostridium, biosynthesis

Description of Research

Studies on ether lipid biosynthesis in anaerobic bacteria.
The polar lipids of aerobic and facultative bacteria are mainly of the diacyl phospholipid or glycolipid type in which the first two carbons of the glycerol backbone are occupied by long-chain fatty acid esters. The situation is different in many anaerobes, including both Gram- positive and negative species, which have both diacyl lipids and plasmalogens in which the chain on the first carbon of glycerol is attached through an O-alk-1’-enyl ether bond. The ratio of the two types varies from species to species
In animal cells, the formation of plasmalogens requires molecular oxygen. But among bacteria only anaerobic species contain plasmalogens, so an oxygen-requiring reaction is not possible. Clearly another pathway is used, which evolved long before these lipids were made by animal cells. The early earth had an anaerobic atmosphere; hence the first living things were anaerobes, presumably the ancestors of present day anaerobes. Indeed, all reactions essential for making bacterial cells including amino acids, purine and pyrimidine bases, lipids and the essential cofactors, are still anaerobic, in line with their anaerobic ancestry. Therefore, it is no surprise that an anaerobic mechanism for making plasmalogens arose first. Present evidence suggests that plasmalogen synthesis in bacteria follows the same pathway used for the formation of diacyl phospholipids starting with glycerol-P and ending with conversion of diacylphospholipids to the corresponding plasmalogens by an unknown mechanism.
The Goldfine laboratory has shown that all the major clostridial pathogens, like other clostridia, contain plasmalogens. Kinetic studies of plasmalogen biosynthesis in clostridia suggested that the corresponding diacyl phospholipids served as precursors to plasmalogens. Furthermore, we have shown that the intermediates in phospholipid biosynthesis in clostridia have no or at most trace amounts of plasmalogens. Recent work has shown a direct conversion of exogenous diacyl lipid to plasmalogens in growing cells of clostridia. Studies continue on this conversion.

Selected Publications

Wei Z., Zenewicz LA., Goldfine H.: Listeria monocytogenes phosphatidylinositol-specific phospholipase C has evolved for virulence by greatly reduced activity on GPI anchors. Proceedings of the National Academy of Sciences of the United States of America 102(36): 12927-31, Sep 6 2005.

Zenewicz LA., Wei Z., Goldfine H., Shen H.: Phosphatidylinositol-specific phospholipase C of Bacillus anthracis down-modulates the immune response. Journal of Immunology 174(12): 8011-6, Jun 15 2005.

Poussin MA., Goldfine H.: Involvement of Listeria monocytogenes phosphatidylinositol-specific phospholipase C and host protein kinase C in permeabilization of the macrophage phagosome. Infection & Immunity 73(7): 4410-3, Jul 2005.

Zenewicz, L.A., Skinner, J.A., Goldfine, H., and Shen, H.: Listeria monocytogenes viroulence proteins induce surface expression of Fas ligand on T cells. Mol. Microbiol(51), 1483-1492, 2004.

Johnston, N.C., Baker, J., and Goldfine, H.: Phospholipids of Clostridium perfringens: A reexamination. FEMS Microbiol. Letters 233(1): 65-68, 2004.

Montes LR., Goni FM., Johnston NC., Goldfine H., Alonso A.: Membrane fusion induced by the catalytic activity of a phospholipase C/sphingomyelinase from Listeria monocytogenes. Biochemistry 43(12): 3688-95, Mar 30 2004.

Wadsworth, S.J. and Goldfine, H. : Mobilization of protein kinase C in macrophages induced by Listeria monocytogenes affects its internalization and escape from phagosome. Infection and Immunity 70: 4650-4660, 2002.

Goldfine, H.: From unsaturated fatty acids to lipid polymorphism. Biochem. Biophys. Res. Commun. 292: 1201-1207, 2002.

Aygun-Sunar, S., Mandaci, S., Koch, H.-G., Murray, I.V.J., Goldfine, H., and Daldal, F. : Orinithine lipid is required for the presence of c-type cytochromes in Rhodobacter capsulatus. Molecular Microbiology 2(61): 418 - 435, 2006.

Poussin, M.A., Leitges, M. and Goldfine, H: The ability of Listeria monocytogenes PI-PLC to facilitate escape from the macrophage phagosome is dependent on host PKC. Microbial Pathogenesis 46(1): 1-5, 2009.

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Last updated: 04/14/2014
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