In a search for agents suitable for isolating cytoplasmically-inherited drug- resistant
mutants, a number of antibiotics, antibacterials, respiratory inhibitors and compounds
known to induce the "petite" phenotype in yeast were examined.
Toxicity tests were performed in 2 mls of Vogel's Medium N in 4-inch stationary test
tubes. Sucrose at 2% (w/v) was used as a fermentable carbon source; sodium acetate at 40
millimolar or glycerol at 2% was employed as a non-fermentable substrate. The pH of the
drug-containing media was either pH 5.8-6.5 (low pH ) or pH 7.5-8.5 (high pH ), and the
growth rate of 74A was found to be reasonably good over this entire range. Germinating
conidia of five-day-old cultures of 74A were added to a final concentration of
approximately 106 conidia/ml, and the cultures were incubated at 34 for 5 days. The
concentrations of the drugs given in Table 1 are either those which permitted no visible
growth in 5 days, or the highest concentrations which, for technical reasons, were tested.
In general, aminoglycoside antibiotics are ineffective, except for kasugamycin and
paromomycin. Macrolides are toxic only at the higher pH and show little discrimination
between fermentable and non-fermentable carbon sources. In fact, a good portion of the
differences seen between the two carbon sources and the two pH's is probably due to the
differences in growth rate observed under these conditions in the absence of any drugs.
This work was supported by USPHS Post-doctoral Fellowship 5-F02-GM-32,085-02 to the author
and Training Grant 5-TOI-GM00367-12 to the Department of Genetics, University of
California at Berkeley.
- - -Research Laboratories, Merck, Sharp and Dokme, Rahway, NJ 07065.
The symbols and abbreviations used in the table are given below:
Symbols ------------------------------------------------ M Molar - - - No measurement * Amount of drug/ml of medium > Growth still observed at this conc. ~ Approximate limit of growth + Solubility limit of drug ± Drug is unstable ug Microgram -------------------------------------------------- Abbreviations -------------------------------------------------- ATA Aurintricarboxyllic Acid CCCP Carbonyl Cyanide m-Chlorophenyl Hydrazone DMSO Dimethyl Sulphoxide HOQNO 2-Heptyl-4-hydroxy-quinoline-N-oxide PAHS Polyamidohygrostreptin TTFA Thenoyltrifluoroacetone TTC Triphenyltetrazolium Chloride --------------------------------------------------Table 1. inhibitory concentrations of Drugs for Neurospora
Low pH Carbon Source High pH Carbon Source
Fermentable Non-fermentable Fermentable Non-fermentable
Acriflavin > 5 ug* 5 ug --- ---
Actinobolin > 1 mg > 1 mg --- ---
Atractylater, K > 1 mg > 1 mg --- ---
Amicetin > 5 mg 2 mg > 1 mg + > 1 mg +
Amobarbital > 1 mg > 1 mg --- ---
Amphotericin B > 1 ug > 1 ug > 1 ug > 1 ug
Antimycin A > 10 ug ~ 1 ug > 1 ug <10 ug
ATA > 5 mg+ > 5 mg+ --- 1 mg+
Azide, Na ~ 10-3M ~ 10-3M --- ---
Benzyl alcohol >0.08% > 0.08% --- ---
Bluensomycin > 20 mg > 20 mg > 20 mg > 20 mg
Brilliant Green > 2 ug > 2 ug --- ---
Carbomycin > 5 mg --- --- ---
CCCP > 1 ug > 1 ug > 1 ug > 1 ug
Chloramphenicol > 4 mg 4 mg --- ---
Chloroquin Phos. --- > 1 mg+ --- ---
Chlorpromazine ~50 ug 50 ug --- ---
Clindamycin --- --- 1.5 mg 1.5 mg
COCl2 -6H20 > 2 mg --- --- ---
Crystal violet 1 ug 1 ug --- ---
Dicoumarol > 5 mg+ > 5 mg+ > 5 mg+ > 5 mg+
DMSO > 2 % > 2 % --- ---
Dinitrophenol ~ 10-3M ~ 10-3M --- ---
Erythromycin > 5 mg > 5 mg 5 mg 5 mg
EthidiumBr > 10 ug > 5 ug --- ---
Fusidic Acid --- > 5 mg+ --- > 5 mg+
Gentamycin > 20 mg > 20 mg > 20 mg 20 mg
Gramicidin D >100 ug >100 ug >100 ug > 100 ug
HOQNO > 1 mg > 1 mg --- ---
Janus Green B.G. 1-2 ug > 1 ug --- ---
Kanamycin > 20 mg > 20 mg > 20 mg > 20 mg
Kasugamycin > 20 mg 5 mg --- ---
Lincomycin > 20 mg > 20 mg > 20 mg > 20 mg
Malachite Green 1 ug 1 ug --- ---
Mikamycin > 2 mg --- --- ---
Naladixic acid >200 ug 100 ug >200 ug >200 ug
Neamine > 20 mg > 20 mg > 20 mg > 20 mg
Neomycin > 20 mg > 20 mg > 20 mg 20 mg
Oleandomycin > 20 mg > 20 mg > 20 mg 20 mg
Oligomycin > 10 ug 10 ug > 10 ug 10 ug
Ouabain --- --- > 5 mg > 5 mg
Oxytetracycline >1 mg ± > 1 mg± --- > 1 mg±
Pararosanilitie > 10 ug 10 ug --- 10 ug
Paromomycin > 10 mg 5 mg 5 mg 5 mg
Pentachlorophenol 5 ug 5 ug 5 ug 5 ug
PAHS 10 ug 5 ug > 10 ug > 10 ug
Pyronine B 100 ug 100 ug 100 ug 100 ug
Pyronine Y >500 ug >500 ug --- ---
Quinine S04 1 mg+ 1 mg+ 1 mg+ 1 mg+
Rifampicin --- > 1 mg+ --- ---
Rotenone > 1 mg > 1 mg --- ---
Rutamycin >200 ug 25 ug 100 ug 25 ug
Safranine 100 ug 100 ug --- ---
Spectinomycin > 20 mg > 20 mg > 20 mg > 20 mg
Spiramycin > 5 mg > 5 mg > 5 mg 5 mg
Staphylomycin > 4 mg+ --- --- ---
Streptogramin > 2 mg+ --- --- ---
Streptomycin > 20 mg > 20 mg --- > 20 mg
Tellurite, K > 1 mg --- --- ---
Tetracycline > 1 mg± 1 mg± 1 mg± > 1 mg±
TTFA >100 ug 100 ug --- ---
Thiomycetin > 4 mg+ --- --- ---
Thiostrepton --- --- > 1 mg+ > 1 mg+
Trimethoprim > 5 mg+ ~ 5 mg+ --- ---
TTC > 1 mg > 1 mg --- ---
Tyrothricin > 50 ug > 50 ug > 50 ug > 50 ug
Valinomycin > 10 ug+ 10 ug 10 ug 10 ug
Vernamycin > 5 mg > 5 mg > 5 mg > 5 mg
Viomycin > 20 mg > 20 mg > 20 mg > 20 mg
Last modified 10/11