Molecular Mechanisms of Antibiotic Action

doi:10.1059/0003-4819-64-5-1087

Molecular Mechanisms of Antibiotic Action

WILLIAM CARTER, M.D.; and
KENNETH S. MCCARTY, PH.D.

Requests for reprints should be addressed to Kenneth S. McCarty, Ph.D., Department of Biochemistry, Duke University,
Durham, N. C.

Excerpt

OUTLINE* I. Introduction

II. Review of the molecular mechanisms of replication, information transfer, and protein synthesis

III. Antibiotics which modify the molecular mechanisms of replication, information transfer, and protein synthesis

A. Assembly of nucleotide substrates Psicofuranine

B. Replication of genetic information Mitomycins, Porfiromycin, Nalidixic Acid and Griseofulvin

C. Transcription of genetic information Actinomycin D

D. Translation of genetic information

1. Amino acid activation

2. The ribosome

a. mRNA binding Chloramphenicol

b. tRNA binding Tetracyclines

c. mRNA translation Streptomycin, Kanamycin and Neomycin

3. Peptide synthesis Puromycin

4. Locus Unclear Erythromycin, Lincomycin

IV. Antibiotics that influence the function or biosynthesis of the

Acknowledgment

The authors wish to thank Drs. Eugene A. Stead, Jr., Phillip Handler, and Robert W. Wheat of the Duke University Medical Center, as well as Hilton B. Levy and B. H. Hoyer of the National Institute of Allergy and Infectious Diseases for their suggestions regarding parts of this manuscript.

Addendum

Since the preparation of this manuscript, lincomycin has been noted to inhibit the ribosomal binding of tRNA, specifically at the 50S ribosomal subunit (CHANG, F. N., SIH, C. J., WEISBLUM, B.: Lincomycin, an inhibitor of aminoacyl sRNA binding to ribosomes. Proc. Nat. Acad. Sci. U. S. A. 55: 431, 1966).

Actinomycin D has recently been shown to inhibit ATP synthesis in leukemic leukocytes respiration and glycolysis (LASZLO, J., MILLER, D. S., MCCARTY, K. S., HOCHSTEIN, P.: Actinomycin D, (inhibition, respiration and glycolysis). Science 151: 1007, 1966).

Summario in Interlingua

Le mechanismo de action de un numero de clinicamente utile antibioticos es revistate intra le quadro de nostre presente conceptiones de replication de information, de transferimento, e de transduction. Iste conceptiones si ben como le structura del membrana de plasma e del pariete bacterio-cellular es commentate.

Le antibioticos es classificate in tres major gruppos comprendente (1) illos que modifica le mechanismos de assemblea e replication de acidos nucleic o que altera le transition de lor information genetic, (2) illos que exerce un influentia super le biosynthese del pariete bacterio-cellular, e (3) illos que altera le function del membrana de plasma.

Article and Author Information

From the Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, N. C.
Dr. Carter, Fellow in Medicine, was supported by training grant 5T1-GM516-05 from the U. S. Public Health Service, Washington, D. C.
Dr. McCarty is an Associate Professor of Biochemistry. His research is supported in part by grants GM-12805-01 and ACS-ACP 363 from the U. S. Public Health Service, Washington, D. C.
↵* Antibiotics in bold face are currently in clinical use.
- Received December 23, 1965.
- Accepted January 6, 1966.