Amplification of specific DNA sequences correlates with resistance of the archaebacterium Halobacterium volcanii to the dihydrofolate reductase inhibitors trimethoprim and methotrexate

Ilan Rosenshine; Tal Zusman; Ruth Werczberger; Moshe Mevarech

doi:10.1007/BF00328149

Amplification of specific DNA sequences correlates with resistance of the archaebacterium Halobacterium volcanii to the dihydrofolate reductase inhibitors trimethoprim and methotrexate

Ilan Rosenshine, Tal Zusman, Ruth Werczberger, Moshe Mevarech^*

^*Corresponding author for this work

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33 Scopus citations

Abstract

The archaebacterium Halobacterium volcanii was found to be very sensitive to the antifolate drugs trimethoprim and methotrexate. Resistant mutants arise spontaneously at a frequency of 10^-10-10^-9. The following evidence is presented which correlates the spontaneous resistance to gene amplification: (a) all resistant mutants have readily observable amplified DNA sequences; (b) the amplified DNA shares common sequences; (c) resistant mutants revert at high frequency to sensitivity, at the same time losing the amplified sequences; (d) there is a genetic linkage between the resistance to trimethoprim and the amplified DNA sequences; (e) all resistant mutants overproduce a 20 kDa protein that corresponds in size to the enzyme dihydrofolate reductase the target of the drugs.

Original language	English
Pages (from-to)	518-522
Number of pages	5
Journal	Zeitschrift fur Vererbungslehre
Volume	208
Issue number	3
DOIs	https://doi.org/10.1007/BF00328149
State	Published - Jul 1987
Externally published	Yes

Keywords

Archaebacterium
DHFR
DNA amplification
Halobacterium
Trimethoprim

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10.1007/BF00328149

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title = "Amplification of specific DNA sequences correlates with resistance of the archaebacterium Halobacterium volcanii to the dihydrofolate reductase inhibitors trimethoprim and methotrexate",

abstract = "The archaebacterium Halobacterium volcanii was found to be very sensitive to the antifolate drugs trimethoprim and methotrexate. Resistant mutants arise spontaneously at a frequency of 10-10-10-9. The following evidence is presented which correlates the spontaneous resistance to gene amplification: (a) all resistant mutants have readily observable amplified DNA sequences; (b) the amplified DNA shares common sequences; (c) resistant mutants revert at high frequency to sensitivity, at the same time losing the amplified sequences; (d) there is a genetic linkage between the resistance to trimethoprim and the amplified DNA sequences; (e) all resistant mutants overproduce a 20 kDa protein that corresponds in size to the enzyme dihydrofolate reductase the target of the drugs.",

keywords = "Archaebacterium, DHFR, DNA amplification, Halobacterium, Trimethoprim",

author = "Ilan Rosenshine and Tal Zusman and Ruth Werczberger and Moshe Mevarech",

year = "1987",

month = jul,

doi = "10.1007/BF00328149",

language = "אנגלית",

volume = "208",

pages = "518--522",

journal = "Zeitschrift fur Vererbungslehre",

issn = "0026-3925",

publisher = "Springer Verlag",

number = "3",

}

Amplification of specific DNA sequences correlates with resistance of the archaebacterium Halobacterium volcanii to the dihydrofolate reductase inhibitors trimethoprim and methotrexate. / Rosenshine, Ilan; Zusman, Tal; Werczberger, Ruth et al.
In: Zeitschrift fur Vererbungslehre, Vol. 208, No. 3, 07.1987, p. 518-522.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Amplification of specific DNA sequences correlates with resistance of the archaebacterium Halobacterium volcanii to the dihydrofolate reductase inhibitors trimethoprim and methotrexate

AU - Rosenshine, Ilan

AU - Zusman, Tal

AU - Werczberger, Ruth

AU - Mevarech, Moshe

PY - 1987/7

Y1 - 1987/7

N2 - The archaebacterium Halobacterium volcanii was found to be very sensitive to the antifolate drugs trimethoprim and methotrexate. Resistant mutants arise spontaneously at a frequency of 10-10-10-9. The following evidence is presented which correlates the spontaneous resistance to gene amplification: (a) all resistant mutants have readily observable amplified DNA sequences; (b) the amplified DNA shares common sequences; (c) resistant mutants revert at high frequency to sensitivity, at the same time losing the amplified sequences; (d) there is a genetic linkage between the resistance to trimethoprim and the amplified DNA sequences; (e) all resistant mutants overproduce a 20 kDa protein that corresponds in size to the enzyme dihydrofolate reductase the target of the drugs.

AB - The archaebacterium Halobacterium volcanii was found to be very sensitive to the antifolate drugs trimethoprim and methotrexate. Resistant mutants arise spontaneously at a frequency of 10-10-10-9. The following evidence is presented which correlates the spontaneous resistance to gene amplification: (a) all resistant mutants have readily observable amplified DNA sequences; (b) the amplified DNA shares common sequences; (c) resistant mutants revert at high frequency to sensitivity, at the same time losing the amplified sequences; (d) there is a genetic linkage between the resistance to trimethoprim and the amplified DNA sequences; (e) all resistant mutants overproduce a 20 kDa protein that corresponds in size to the enzyme dihydrofolate reductase the target of the drugs.

KW - Archaebacterium

KW - DHFR

KW - DNA amplification

KW - Halobacterium

KW - Trimethoprim

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JO - Zeitschrift fur Vererbungslehre

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Amplification of specific DNA sequences correlates with resistance of the archaebacterium Halobacterium volcanii to the dihydrofolate reductase inhibitors trimethoprim and methotrexate

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Keywords

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