Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1992 May;36(5):1081–1085. doi: 10.1128/aac.36.5.1081

Intracellular activity of zidovudine (3'-azido-3'-deoxythymidine, AZT) against Salmonella typhimurium in the macrophage cell line J774-2.

J L Herrmann 1, P H Lagrange 1
PMCID: PMC188839  PMID: 1510397

Abstract

The antibacterial effect of zidovudine (AZT) has been demonstrated both in vitro and in vivo with experimental models of gram-negative bacterial infections. It has been associated with the absence or low occurrence of nontyphoid Salmonella infections in AIDS patients treated with AZT. Using the macrophage cell line J774-2, we demonstrate the inhibition of intracellular growth of Salmonella typhimurium by AZT. This effect is obtained with one-half of the MIC (1 microgram/ml) of AZT for S. typhimurium. Inhibition of intracellular growth is observed after 4 h of incubation and persists at 24 h. Maximal inhibition is shown at a concentration of 128 micrograms/ml, and no further effect is observed with higher concentrations. When the inhibitory effect of AZT is compared with that of pefloxacin or that of ceftriaxone at half their MICs (0.2 and 0.02 microgram/ml, respectively), AZT and pefloxacin give better results than ceftriaxone. In this study, using an intracellular model, we show that AZT is able to inhibit the intracellular multiplication of S. typhimurium at a minimal effective concentration lower than the MIC, indicating its potential for antibacterial accumulation in the macrophages.

Full text

PDF
1081

Selected References

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

  1. Celum C. L., Chaisson R. E., Rutherford G. W., Barnhart J. L., Echenberg D. F. Incidence of salmonellosis in patients with AIDS. J Infect Dis. 1987 Dec;156(6):998–1002. doi: 10.1093/infdis/156.6.998. [DOI] [PubMed] [Google Scholar]
  2. Dellamonica P., Mondain V., Bernard E. Aspect thérapeutique des salmonelloses au cours du SIDA. Pathol Biol (Paris) 1990 Apr;38(4):298–301. [PubMed] [Google Scholar]
  3. Elwell L. P., Ferone R., Freeman G. A., Fyfe J. A., Hill J. A., Ray P. H., Richards C. A., Singer S. C., Knick V. B., Rideout J. L. Antibacterial activity and mechanism of action of 3'-azido-3'-deoxythymidine (BW A509U). Antimicrob Agents Chemother. 1987 Feb;31(2):274–280. doi: 10.1128/aac.31.2.274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fields P. I., Groisman E. A., Heffron F. A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells. Science. 1989 Feb 24;243(4894 Pt 1):1059–1062. doi: 10.1126/science.2646710. [DOI] [PubMed] [Google Scholar]
  5. Fields P. I., Swanson R. V., Haidaris C. G., Heffron F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5189–5193. doi: 10.1073/pnas.83.14.5189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Finlay B. B., Falkow S. Common themes in microbial pathogenicity. Microbiol Rev. 1989 Jun;53(2):210–230. doi: 10.1128/mr.53.2.210-230.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Furman P. A., Fyfe J. A., St Clair M. H., Weinhold K., Rideout J. L., Freeman G. A., Lehrman S. N., Bolognesi D. P., Broder S., Mitsuya H. Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8333–8337. doi: 10.1073/pnas.83.21.8333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Keith B. R., White G., Wilson H. R. In vivo efficacy of zidovudine (3'-azido-3'-deoxythymidine) in experimental gram-negative-bacterial infections. Antimicrob Agents Chemother. 1989 Apr;33(4):479–483. doi: 10.1128/aac.33.4.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lewin C. S., Allen R. A., Amyes S. G. Mechanisms of zidovudine resistance in bacteria. J Med Microbiol. 1990 Dec;33(4):235–238. doi: 10.1099/00222615-33-4-235. [DOI] [PubMed] [Google Scholar]
  10. Lewin C. S., Allen R., Amyes S. G. Zidovudine-resistance in Salmonella typhimurium and Escherichia coli. J Antimicrob Chemother. 1990 Apr;25(4):706–708. doi: 10.1093/jac/25.4.706. [DOI] [PubMed] [Google Scholar]
  11. Lewin C. S., Amyes S. G. Conditions required for the antibacterial activity of zidovudine. Eur J Clin Microbiol Infect Dis. 1989 Aug;8(8):737–741. doi: 10.1007/BF01963765. [DOI] [PubMed] [Google Scholar]
  12. Lewin C. S., Watt B., Paton R., Amyes S. G. Isolation of zidovudine resistant Escherichia coli from AIDS patients. FEMS Microbiol Lett. 1990 Jul;58(2):141–143. doi: 10.1111/j.1574-6968.1990.tb13967.x. [DOI] [PubMed] [Google Scholar]
  13. Mitsuya H., Weinhold K. J., Furman P. A., St Clair M. H., Lehrman S. N., Gallo R. C., Bolognesi D., Barry D. W., Broder S. 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096–7100. doi: 10.1073/pnas.82.20.7096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Salmon D., Detruchis P., Leport C., Bouvet E., Karam D., Meyohas M. C., Coulaud J. P., Vildé J. L. Efficacy of zidovudine in preventing relapses of Salmonella bacteremia in AIDS. J Infect Dis. 1991 Feb;163(2):415–416. doi: 10.1093/infdis/163.2.415. [DOI] [PubMed] [Google Scholar]
  15. Schwarzbaum S., Diamond B. The J744.2 cell line presents antigen in an I region restricted manner. J Immunol. 1983 Aug;131(2):674–677. [PubMed] [Google Scholar]
  16. Sperber S. J., Schleupner C. J. Salmonellosis during infection with human immunodeficiency virus. Rev Infect Dis. 1987 Sep-Oct;9(5):925–934. doi: 10.1093/clinids/9.5.925. [DOI] [PubMed] [Google Scholar]
  17. Vladoianu I. R., Chang H. R., Pechère J. C. Expression of host resistance to Salmonella typhi and Salmonella typhimurium: bacterial survival within macrophages of murine and human origin. Microb Pathog. 1990 Feb;8(2):83–90. doi: 10.1016/0882-4010(90)90072-x. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES