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. 1975 Mar;7(3):349–363. doi: 10.1128/aac.7.3.349

Inhibitory Effects of Lipophilic Acids and Related Compounds on Bacteria and Mammalian Cells

C W Sheu 1,2,1, D Salomon 1,2, J L Simmons 1,2, T Sreevalsan 1,2, E Freese 1,2
PMCID: PMC429138  PMID: 1137388

Abstract

The inhibitory effect of lipophilic acids, antimicrobial food additives, and analgesics-antipyretics was examined at concentrations from 0.1 to 100 mM in bacteria (Bacillus subtilis and Escherichia coli) and mammalian cells (HeLa, human fibroblasts, and mouse neuroblastoma cells). Most compounds inhibit the growth of HeLa cells about as efficiently as that of B. subtilis. However, butyrate and propionate, as well as acetaminophen, antipyrene, phenacetin, and salicylamide, inhibit HeLa at millimolar concentrations whereas, at least 10 times higher concentrations are needed to inhibit B. subtilis. The concentrations needed to inhibit growth by 50% decrease with increasing octanol-water partition coefficients of the compound. Growth of E. coli is inhibited similar to that of B. subtilis by all compounds except butylbenzoate, decanoate, and linoleate which cannot penetrate the lipopolysaccharide layer. All growth inhibitors inhibit amino acid uptake into bacteria and their vesicles, and oxygen consumption in bacteria. In HeLa cells or human fibroblasts, neither amino acid uptake nor adenine 5′-triphosphate synthesis are inhibited by fatty acids at concentrations that completely inhibit growth. Short chain fatty acids (propionate, butyrate, and pentanoate) induce in HeLa the formation of cell processes. In neuroblastoma cells, grown in the presence of 10% fetal calf serum, butyrate also induces such processes which slowly continue to grow in length for at least 7 days; these processes differ in speed of formation, width, and cycloheximide susceptibility from the thin processes produced by serum deprivation alone.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. DULBECCO R., VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. doi: 10.1084/jem.99.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. doi: 10.1126/science.130.3373.432. [DOI] [PubMed] [Google Scholar]
  3. Fishman P. H., Simmons J. L., Brady R. O., Freese E. Induction of glycolipid biosynthesis by sodium butyrate in HeLa cells. Biochem Biophys Res Commun. 1974 Jul 10;59(1):292–299. doi: 10.1016/s0006-291x(74)80205-6. [DOI] [PubMed] [Google Scholar]
  4. Foster D. O., Pardee A. B. Transport of amino acids by confluent and nonconfluent 3T3 and polyoma virus-transformed 3T3 cells growing on glass cover slips. J Biol Chem. 1969 May 25;244(10):2675–2681. [PubMed] [Google Scholar]
  5. Freese E., Sheu C. W., Galliers E. Function of lipophilic acids as antimicrobial food additives. Nature. 1973 Feb 2;241(5388):321–325. doi: 10.1038/241321a0. [DOI] [PubMed] [Google Scholar]
  6. Ginsburg E., Salomon D., Sreevalsan T., Freese E. Growth inhibition and morphological changes caused by lipophilic acids in mammalian cells. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2457–2461. doi: 10.1073/pnas.70.8.2457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kirkland W. L., Burton P. R. Cyclic adenosine monophosphate-mediated stabilization of mouse neuroblastoma cell neuritis microtubules exposed to low temperature. Nat New Biol. 1972 Dec 13;240(102):205–207. doi: 10.1038/newbio240205a0. [DOI] [PubMed] [Google Scholar]
  8. Klofat W., Picciolo G., Chappelle E. W., Freese E. Production of adenosine triphosphate in normal cells and sporulation mutants of Bacillus subtilis. J Biol Chem. 1969 Jun 25;244(12):3270–3276. [PubMed] [Google Scholar]
  9. Konings W. N., Freese E. Amino acid transport in membrane vesicles of Bacillus subtilis. J Biol Chem. 1972 Apr 25;247(8):2408–2418. [PubMed] [Google Scholar]
  10. Prasad K. N., Waymire J. C., Weiner N. A further study on the morphology and biochemistry of x-ray and dibutyryl cyclic AMP-induced differentiated neuroblastoma cells in culture. Exp Cell Res. 1972 Sep;74(1):110–114. doi: 10.1016/0014-4827(72)90485-5. [DOI] [PubMed] [Google Scholar]
  11. Seeds N. W., Gilman A. G., Amano T., Nirenberg M. W. Regulation of axon formation by clonal lines of a neural tumor. Proc Natl Acad Sci U S A. 1970 May;66(1):160–167. doi: 10.1073/pnas.66.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sheu C. W., Freese E. Effects of fatty acids on growth and envelope proteins of Bacillus subtilis. J Bacteriol. 1972 Aug;111(2):516–524. doi: 10.1128/jb.111.2.516-524.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sheu C. W., Freese E. Lipopolysaccharide layer protection of gram-negative bacteria against inhibition by long-chain fatty acids. J Bacteriol. 1973 Sep;115(3):869–875. doi: 10.1128/jb.115.3.869-875.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sheu C. W., Konings W. N., Freese E. Effects of acetate and other short-chain fatty acids on sugar and amino acid uptake of Bacillus subtilis. J Bacteriol. 1972 Aug;111(2):525–530. doi: 10.1128/jb.111.2.525-530.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]

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