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Howard Goldfine, Ph.D.

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

Guan, Z., Tian, B., Perfumo, A. and Goldfine, H. : The polar lipids of Clostridium psychrophilum, an anaerobic psychrophile. Biochim. Biophys. Acta., Biochim. Biophys. Acta 18321(6), 2013.

Tian, B., Guan, Z. and Goldfine, H. : An ethanolamine-phosphate modified glycolipid in Clostridium acetobutylicum that responds to membrane stress. Biochim. Biophys. Acta 1831: :1185-1190 2013.

Guan Ziqiang, Johnston Norah C, Raetz Christian R H, Johnson Eric A, Goldfine Howard: Lipid diversity among botulinum neurotoxin-producing clostridia. Microbiology (Reading, England) 158(Pt 10): 2577-84, Oct 2012.

Guan Ziqiang, Johnston Norah C, Aygun-Sunar Semra, Daldal Fevzi, Raetz Christian R H, Goldfine Howard: Structural characterization of the polar lipids of Clostridium novyi NT. Further evidence for a novel anaerobic biosynthetic pathway to plasmalogens. Biochimica et biophysica acta 1811(3): 186-93, Mar 2011.

Poussin, M. A. and Goldfine, H. : Evidence for involvement of ActA in maturation of the Listeria monocytogenes phagosome. Cell Research 20(1): 109-112, 2010.

Johnston, N.C., Aygun-Sunar, S., Guan, Z., Ribeiro, A.A., Daldal, F., Raetz, C.R., and Goldfine, H: A phosphoethanolamine-modified glycosyl diradylglycerol in the polar Lipids of Clostridium tetani. J. Lipid Res. 51: 1953-1961, 2010.

Goldfine, H.: The appearance, disappearance and reappearance of plasmalogens in evolution. Prog. Lipid Res. in press, 2010.

Goldfine, H.: Membrane biogenesis. Timmis, K.N. Ed., Handbook of Hydrocarbon and Lipid Microbiology. 417-424 (eds.). Springer Verlag, 1, 2010.

Vasil, M.L., Stonehouse, M.J., Vasil, A.I., Wadsworth, S.J., Goldfine, H., Bolcome, R.E. III and Chan, J. A : Complex Extracellular Sphingomyelinase of Pseudomonas aeruginosa Inhibits Angiogenesis by Selective Cytotoxicity to Endothelial Cells. PloS Pathogens 5: e1000420, 2009.

Chen, W., Goldfine, H., Ananthanarayanan, B. Cho, W., and Roberts, M.F. : Listeria monocytogenes phosphatidylinositol-specific phospholipase C:Kinetic activation and homing in on different interfaces. Biochemistry 48: 3578-3592, 2009.

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Last updated: 04/14/2014
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