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Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress.
Mol Microbiol. 2000 Feb; 35(3):542-52.MM

Abstract

In Kinetoplastida, trypanothione and trypanothione reductase (TRYR) provide an intracellular reducing environment, substituting for the glutathione-glutathione reductase system found in most other organisms. To investigate the physiological role of TRYR in Trypanosoma brucei, we generated cells containing just one trypanothione reductase gene, TRYR, which was under the control of a tetracycline-inducible promoter. This enabled us to regulate TRYR activity in the cells from less than 1% to 400% of wild-type levels by adjusting the concentration of added tetracycline. In normal growth medium (which contains reducing agents), trypanosomes containing less than 10% of wild-type enzyme activity were unable to grow, although the levels of reduced trypanothione and total thiols remained constant. In media lacking reducing agents, hypersensitivity towards hydrogen peroxide (EC50 = 3.5 microM) was observed compared with the wild type (EC50 = 223 microM). The depletion of TRYR had no effect on susceptibility to melarsen oxide. The infectivity and virulence of the parasites in mice was dependent upon tetracycline-regulated TRYR activity: if the trypanosomes were injected into mice in the absence of tetracycline, no infection was detectable; and when tetracycline was withdrawn from previously infected animals, the parasitaemia was suppressed.

Authors+Show Affiliations

Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10672177

Citation

Krieger, S, et al. "Trypanosomes Lacking Trypanothione Reductase Are Avirulent and Show Increased Sensitivity to Oxidative Stress." Molecular Microbiology, vol. 35, no. 3, 2000, pp. 542-52.
Krieger S, Schwarz W, Ariyanayagam MR, et al. Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Mol Microbiol. 2000;35(3):542-52.
Krieger, S., Schwarz, W., Ariyanayagam, M. R., Fairlamb, A. H., Krauth-Siegel, R. L., & Clayton, C. (2000). Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Molecular Microbiology, 35(3), 542-52.
Krieger S, et al. Trypanosomes Lacking Trypanothione Reductase Are Avirulent and Show Increased Sensitivity to Oxidative Stress. Mol Microbiol. 2000;35(3):542-52. PubMed PMID: 10672177.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. AU - Krieger,S, AU - Schwarz,W, AU - Ariyanayagam,M R, AU - Fairlamb,A H, AU - Krauth-Siegel,R L, AU - Clayton,C, PY - 2000/2/15/pubmed PY - 2000/4/1/medline PY - 2000/2/15/entrez SP - 542 EP - 52 JF - Molecular microbiology JO - Mol Microbiol VL - 35 IS - 3 N2 - In Kinetoplastida, trypanothione and trypanothione reductase (TRYR) provide an intracellular reducing environment, substituting for the glutathione-glutathione reductase system found in most other organisms. To investigate the physiological role of TRYR in Trypanosoma brucei, we generated cells containing just one trypanothione reductase gene, TRYR, which was under the control of a tetracycline-inducible promoter. This enabled us to regulate TRYR activity in the cells from less than 1% to 400% of wild-type levels by adjusting the concentration of added tetracycline. In normal growth medium (which contains reducing agents), trypanosomes containing less than 10% of wild-type enzyme activity were unable to grow, although the levels of reduced trypanothione and total thiols remained constant. In media lacking reducing agents, hypersensitivity towards hydrogen peroxide (EC50 = 3.5 microM) was observed compared with the wild type (EC50 = 223 microM). The depletion of TRYR had no effect on susceptibility to melarsen oxide. The infectivity and virulence of the parasites in mice was dependent upon tetracycline-regulated TRYR activity: if the trypanosomes were injected into mice in the absence of tetracycline, no infection was detectable; and when tetracycline was withdrawn from previously infected animals, the parasitaemia was suppressed. SN - 0950-382X UR - https://www.unboundmedicine.com/medline/citation/10672177/Trypanosomes_lacking_trypanothione_reductase_are_avirulent_and_show_increased_sensitivity_to_oxidative_stress_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0950-382X&date=2000&volume=35&issue=3&spage=542 DB - PRIME DP - Unbound Medicine ER -