Jack L. Strominger. Reprinted, with permission, from the Annual Review of Immunology, Vol. 24. ©2006 by Annual Reviews, www.annualreviews.org.
Multiple Penicillin-binding Components in Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, and Escherichia coli (Suginaka, H., Blumberg, P. M., and Strominger, J. L. (1972) J. Biol. Chem. 247, 5279–5288)
Five Penicillin-binding Components Occur in Bacillus subtilis Membranes (Blumberg, P. M., and Strominger, J. L. (1972) J. Biol. Chem. 247, 8107–8113)
Jack L. Strominger was born in 1925 in New York City. He attended Harvard University where he majored in psychology and took the minimum number of courses that would get him into medical school. He completed his degree in 1944, after which the Navy assigned him as a corpsman to Chelsea Naval Hospital. After 5 months at the hospital, Strominger was admitted to Yale Medical School where he served as a naval trainee.
During his first year in medical school, Strominger got a job helping John Brobeck, an assistant professor in physiology, study hypothalamic hyperphagia in rats. The job lasted through medical school, and Strominger wrote his thesis on the research. This experience got Strominger, who was previously not interested in science, hooked on research.
Strominger received his M.D. in 1948 and obtained an internship in internal medicine on the Ward Medical Service at Barnes Hospital in St. Louis affiliated with Washington University School of Medicine. Strominger recalls, “I did not like being an intern. It seemed very routine. I decided not to pursue a residency but instead to become a postdoctoral fellow (
1
).” He applied to work with Journal of Biological Chemistry (JBC) Classic author Oliver H. Lowry (2
), who was chairman of the Department of Pharmacology at Washington University. He stayed with Lowry for 2 years, but his research did not go very well. Discouraged, Strominger decided to finish his residency in medicine at the University of Chicago.Soon after he made this decision, the Korean War started and Strominger learned that Washington University School of Medicine had been asked to help vitalize medical education in Bangkok, Thailand, by providing staff for the medical school at Siriraj Hospital. He joined the program as an officer in the U.S. Public Health Service. However, Strominger's time in Thailand was cut short when he was asked to resign his commission because he was believed to be a security risk. He was charged with (a) having friends who were allegedly members of the Communist Party, (b) having a library of communist books, and (c) subscribing to the Daily Worker, the publication of the American Communist Party. Strominger was able to show that (a) his communist friends were actually members of the Association of Interns and Medical Students, which was branded as a communist organization by the American Medical Association because it campaigned for the introduction of health insurance in the U.S., (b) his library of communist books was actually required reading for a political science course he had taken at Yale, and (c) his Daily Worker subscription was actually a subscription for the Progressive. Although innocent of the charges, Strominger did not return to Bangkok and was instead assigned to the National Institutes of Health for the remainder of his appointment as a commissioned officer.
At the NIH, Strominger worked in Sanford Rosenthal's laboratory at the NIAMD. He decided to work on the mechanism of penicillin action, focusing on an unusual nucleotide that had been isolated from penicillin-inhibited staphylococci by James T. Park. The nucleotide contained uridine diphosphate, linked to a previously undescribed sugar, which was linked to a peptide. Strominger was able to come up with a new method for measuring the accumulation of this nucleotide.
After 2 years at the NIH, Strominger accepted an invitation from Oliver Lowry to become an assistant professor in the pharmacology department at Washington University. He arrived in St. Louis in 1956 after taking a year's sabbatical in Europe during which he worked out the sequence of the pentapeptide in UDP-acetylmuramyl-pentapeptide, the Park nucleotide. Strominger spent the next 8 years showing that the nucleotide was a biosynthetic precursor of the bacterial cell wall, isolating cell walls, determining their structure, and determining the mode of biosynthesis of UDP-acetylmuramyl-pentapeptide.
In 1964, Strominger accepted an offer to become chairman of the pharmacology department at the University of Wisconsin. There, he continued to study bacterial cell wall biosynthesis, testing each new step he discovered for sensitivity to penicillin. He was able to show that the formation of cross-bridges in the cell wall was inhibited by penicillin, which inactivated the transpeptidase that catalyzed the cross-linking of the bacterial cell wall. However, it was unclear whether penicillin bound to just one or to many components in bacteria.
In the first JBC Classic reprinted here, Strominger and his colleagues report that Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, and Escherichia coli have many penicillinbinding components. Using paper electrophoresis (SDS gels had not yet been introduced) they found that virtually all of the penicillin binding sites are located in the cell membrane and that all of the organisms had not one, but multiple penicillin-binding proteins. Thus they conclude, “killing of the bacterial cell might result either from interaction with a given one of the components or else from interaction with any one of several of the penicillin-binding components. Similarly, interaction with some of the components may not result in a lethal effect on the bacterial cell.”
The phenomenon of multiple penicillin-binding components became much clearer in the second JBC Classic with the use of immunoaffinity chromatography and SDS gels. Strominger and Peter M. Blumberg used [14C]penicillin G to show that B. subtilis contained five penicillinbinding components. The major penicillin-binding component, V, was identified as the d-alanine carboxypeptidase, the activity of which was not vital for the cell. Three of the other components, in contrast, bound penicillins and cephalosporins at rates comparable to that of the penicillin killing site in B. subtilis.
In 1968, Strominger was invited to join the new Department of Biochemistry and Molecular Biology at Harvard University. With this move, Strominger also switched fields, concentrating on human HLA proteins. In collaboration with Don Wiley, he isolated, crystallized, and elucidated the three-dimensional structures of these molecules and showed that their principal function was to present peptides to the immune system in initiating an immune response. More recently, Strominger's laboratory has focused on natural killer cells and their roles in peripheral blood and in the pregnant uterine decidua. Strominger remains at Harvard today where he is Higgins Professor of Biochemistry.
Strominger has received several awards and honors in recognition of his contributions to science. These include the 1995 Albert Lasker Basic Medical Research Award, the 1996 Paul Ehrlich Prize, the 1999 Japan Prize from the Science and Technology Foundation of Japan, and the 1999 Klemperer Award from the New York Academy of Medicine. He was elected to the National Academy of Sciences in 1970 and the National Institute of Medicine in 1975.
References
- Annu. Rev. Immunol. 2006; 24 (The tortuous journey of a biochemist to immunoland and what he found there.): 1-31
JBC Classics: Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951) J. Biol. Chem., 193, 265–275 (http://www.jbc.org/cgi/content/full/280/28/e25)
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