Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1994 Feb;38(2):189–194. doi: 10.1128/aac.38.2.189

Subcellular distribution of daptomycin given alone or with tobramycin in renal proximal tubular cells.

D Beauchamp 1, P Gourde 1, M Simard 1, M G Bergeron 1
PMCID: PMC284424  PMID: 8192441

Abstract

Previous studies in experimental animals showed that daptomycin, a lipopeptide antibiotic, protects against aminoglycoside nephrotoxicity (C. A. Wood, H. C. Finkbeiner, S. J. Kohlhepp, P. W. Kohnen, and D. N. Gilbert, Antimicrob. Agents Chemother. 33:1280-1285, 1989; D. Beauchamp, M. Pellerin, P. Gourde, M. Pettigrew, and M. G. Bergeron, Antimicrob. Agents Chemother. 34:139-147, 1990). In order to better understand the mechanism involved in this protective effect, the subcellular distribution of daptomycin was investigated in the proximal tubular cells of animals treated with daptomycin alone or in combination with tobramycin. A first group of female Sprague-Dawley rats received a single intravenous injection of daptomycin at a dose of 100 mg/kg of body weight and were killed at 10 min, 1 h, or 24 h after the injection. Other groups of rats were treated during 10 days with saline (NaCl, 0.9%), tobramycin at dosages of 20 mg/kg/12 h, daptomycin at dosages of 10 mg/kg/12 h, or the combination tobramycin-daptomycin at the same dosages. At the time of sacrifice, the renal cortex of the right kidney of each animal was dissected, and small blocks of tissue were fixed, dehydrated, and embedded in Araldite 502 epoxy resin. The subcellular distribution of daptomycin and tobramycin was determined on ultrathin sections by immunogold labeling. Ten minutes after the injection of daptomycin alone, gold particles were seen over the brush border membrane and on the membranes of the endocytic vacuoles of proximal tubular cells. One hour after the injection, a similar distribution was seen and numerous gold particles were found over the lysosomes of proximal tubular cells. The results suggest that daptomycin might protect against aminoglycoside nephrotoxicity by interfering with the interaction between the aminoglycoside and phospholipids inside the lysosomes of proximal tubular cells.

Full text

PDF
189

Images in this article

Selected References

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

  1. Beauchamp D., Gourde P., Bergeron M. G. Subcellular distribution of gentamicin in proximal tubular cells, determined by immunogold labeling. Antimicrob Agents Chemother. 1991 Nov;35(11):2173–2179. doi: 10.1128/aac.35.11.2173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beauchamp D., Gourde P., Simard M., Bergeron M. G. Subcellular localization of tobramycin and vancomycin given alone and in combination in proximal tubular cells, determined by immunogold labeling. Antimicrob Agents Chemother. 1992 Oct;36(10):2204–2210. doi: 10.1128/aac.36.10.2204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beauchamp D., Pellerin M., Gourde P., Pettigrew M., Bergeron M. G. Effects of daptomycin and vancomycin on tobramycin nephrotoxicity in rats. Antimicrob Agents Chemother. 1990 Jan;34(1):139–147. doi: 10.1128/aac.34.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bergeron M. G., Marois Y., Kuehn C., Silverblatt F. J. Autoradiographic study of tobramycin uptake by proximal and distal tubules of normal and pyelonephritic rats. Antimicrob Agents Chemother. 1987 Sep;31(9):1359–1364. doi: 10.1128/aac.31.9.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Giurgea-Marion L., Toubeau G., Laurent G., Heuson-Stiennon J. A., Tulkens P. M. Impairment of lysosome-pinocytic vesicle fusion in rat kidney proximal tubules after treatment with gentamicin at low doses. Toxicol Appl Pharmacol. 1986 Nov;86(2):271–285. doi: 10.1016/0041-008x(86)90058-x. [DOI] [PubMed] [Google Scholar]
  6. Roth J., Bendayan M., Orci L. Ultrastructural localization of intracellular antigens by the use of protein A-gold complex. J Histochem Cytochem. 1978 Dec;26(12):1074–1081. doi: 10.1177/26.12.366014. [DOI] [PubMed] [Google Scholar]
  7. Roth J. The preparation of protein A-gold complexes with 3 nm and 15nm gold particles and their use in labelling multiple antigens on ultra-thin sections. Histochem J. 1982 Sep;14(5):791–801. doi: 10.1007/BF01033628. [DOI] [PubMed] [Google Scholar]
  8. Silverblatt F. J., Kuehn C. Autoradiography of gentamicin uptake by the rat proximal tubule cell. Kidney Int. 1979 Apr;15(4):335–345. doi: 10.1038/ki.1979.45. [DOI] [PubMed] [Google Scholar]
  9. Tapia F. J., Varndell I. M., Probert L., De Mey J., Polak J. M. Double immunogold staining method for the simultaneous ultrastructural localization of regulatory peptides. J Histochem Cytochem. 1983 Jul;31(7):977–981. doi: 10.1177/31.7.6189888. [DOI] [PubMed] [Google Scholar]
  10. Wood C. A., Finkbeiner H. C., Kohlhepp S. J., Kohnen P. W., Gilbert D. N. Influence of daptomycin on staphylococcal abscesses and experimental tobramycin nephrotoxicity. Antimicrob Agents Chemother. 1989 Aug;33(8):1280–1285. doi: 10.1128/aac.33.8.1280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Wood C. A., Kohlhepp S. J., Kohnen P. W., Houghton D. C., Gilbert D. N. Vancomycin enhancement of experimental tobramycin nephrotoxicity. Antimicrob Agents Chemother. 1986 Jul;30(1):20–24. doi: 10.1128/aac.30.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES