The development of drug-resistant strains of Eimeria maxima in the laboratory

The development of strains of Eimeria maxima resistant to buquinolate, methyl benzoquate, clopidol, sulphaquinoxaline and robenidine is described. It was not possible to standardize a schedule of inoculations and drug administration, which would enable the development of resistance to the different drugs to be compared directly. Resistance developed most readily to the quinolones. One robenidine-resistant strain proved to be drug-dependent. Dinitolmide showed unusual effects upon sporogony and three attempts to develop resistance against this activity failed. Chicks previously immunized with the parent strain were completely protected against infection with the drug-resistant strains.

Download Full-text

Novel isoniazid derivative as promising antituberculosis agent

Future Microbiology ◽

10.2217/fmb-2019-0085 ◽

2020 ◽

Vol 15 (10) ◽

pp. 869-879

Author(s):

Galyna P Volynets ◽

Michail A Tukalo ◽

Volodymyr G Bdzhola ◽

Nataliia M Derkach ◽

Mykola I Gumeniuk ◽

...

Keyword(s):

Resistant Strain ◽

Inhibitory Concentration ◽

Binding Assay ◽

Isonicotinic Acid ◽

Drug Resistant ◽

Major Focus ◽

Unbound Fraction ◽

Protein Binding Assay ◽

Resistant Strains ◽

Drug Resistant Strains

Background: A major focus of tuberculosis drug discovery is aimed at the development of novel antibiotics with activity against drug-resistant strains of Mycobacterium tuberculosis. Results: We have synthesized ten isoniazid derivatives and investigated for antibacterial activity toward M. tuberculosis H37Rv and isoniazid-resistant strain SRI 1369. It was revealed that only one compound, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide (1), is active toward isoniazid-resistant strain with minimum inhibitory concentration value of 0.14 μM. This compound is not cytotoxic toward human liver cells (HepG2; IC50 >100 μM), demonstrates good permeability in Caco-2 cells. Accordingly to the results of plasma protein binding assay, unbound fraction of compound 1, which potentially exhibits pharmacologic effects, is 57.9%. Conclusion: Therefore, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide is a promising compound for further preclinical studies.

Download Full-text

Transferred drug-resistance in Eimeria maxima

Parasitology ◽

10.1017/s0031182000047168 ◽

1975 ◽

Vol 71 (3) ◽

pp. 385-392 ◽

Cited By ~ 24

Author(s):

L. P. Joyner ◽

C. C. Norton

Keyword(s):

Drug Resistance ◽

The Other ◽

Drug Resistant ◽

Resistance Factors ◽

Eimeria Maxima ◽

Series Of Experiments ◽

Resistant Strains ◽

Drug Resistant Strains

A series of experiments is described in which two drug-resistant strains of Eimeria maxima were passaged together in untreated chicks. The resultant oocysts were then inoculated into chicks treated with both drugs. When strains resistant to methyl benzoquate and sulphaquinoxaline or clopidol and sulphaquinoxaline were used the resultant infections were not controlled by the double treatment, indicating the acquisition of resistance factors by one strain from the other. When strains resistant to clopidol and methyl benzoquate were used the phenomenon was not observed.

Download Full-text

Modified Fixed-Ratio Isobologram Method for Studying In Vitro Interactions between Atovaquone and Proguanil or Dihydroartemisinin against Drug-Resistant Strains of Plasmodium falciparum

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.11.4097-4102.2004 ◽

2004 ◽

Vol 48 (11) ◽

pp. 4097-4102 ◽

Cited By ~ 163

Author(s):

Quinton L. Fivelman ◽

Ipemida S. Adagu ◽

David C. Warhurst

Keyword(s):

Plasmodium Falciparum ◽

Treatment Failure ◽

Resistant Strain ◽

Fixed Ratio ◽

Drug Resistant ◽

Resistant Strains ◽

Drug Resistant Strains ◽

In Vitro Interactions

ABSTRACT A modified fixed-ratio isobologram method for studying the in vitro interactions between antiplasmodial drugs is described. This method was used to examine the interactions between atovaquone, proguanil, and dihydroartemisinin. The interaction between atovaquone and proguanil was synergistic against atovaquone-sensitive strains K1 and T996; however, there was a loss of synergy against atovaquone-resistant strain NGATV01 isolated after Malarone (the combination of atovaquone and proguanil) treatment failure. While the interaction between atovaquone and dihydroartemisinin was indifferent against isolate NGATV01, the interaction displayed indifference tending toward antagonism against the atovaquone-sensitive strains tested. The relevance of in vitro interactions to in vivo treatment is discussed.

Download Full-text

Immunity in trypanosomiasis

Parasitology ◽

10.1017/s0031182000026780 ◽

1959 ◽

Vol 49 (1-2) ◽

pp. 143-152 ◽

Cited By ~ 17

Author(s):

M. A. Soltys

Keyword(s):

Resistant Strain ◽

Therapeutic Dose ◽

Sensitive Strain ◽

Drug Resistant ◽

Chemotherapeutic Drugs ◽

Natural Conditions ◽

Resistant Strains ◽

Drug Resistant Strains

Antibody-resistant strains are less sensitive to suramin and antrycide than antibody-sensitive strains. When living trypanosomes were exposed to suramin and antrycide in vitro, antibody-resistant strains needed 50 times more drugs than antibody-sensitive trypanosomes in order to make them non-infectious to mice. In therapeutic experiments in mice the minimal therapeutic dose of drugs for antibody-sensitive strains was 0·1 mg. but for resistant strains it was 0·3 mg./20 g. mice. Rabbits treated prophylactically with suramin resisted infection with the antibody-sensitive strain for a period of 4 months, but failed to resist infection with the antibody-resistant strain after 2 months.Rabbits treated prophylactically with antrycide pro-salt, resisted infection with antibody-sensitive strains for a period of 2 months, but failed to resist infection with the antibody-resistant strain even 1 month after injection with the drug. Although trypanosomes can become drug resistant without being antibody resistant it is suggested that, under natural conditions, drug-resistant strains in animals and man develop from antibody-resistant strains, particularly when trypanostatic drugs are used. It is suggested in conclusion from these experiments that strains of trypanosomes which are exposed for some time to antibodies and become antibody resistant after passage through animals like rabbits, as well as those strains frequently passaged through mice, should be used in all tests for the efficiency of chemotherapeutic drugs.

Download Full-text

The development of resistance to glycarbylamide and 2-chloro-4-nitrobenzamide in Eimeria tenella in chicks

Parasitology ◽

10.1017/s0031182000071067 ◽

1966 ◽

Vol 56 (1) ◽

pp. 25-37 ◽

Cited By ~ 13

Author(s):

S. J. Ball

Keyword(s):

Drug Resistance ◽

Resistant Strain ◽

Parent Strain ◽

Technical Assistance ◽

Eimeria Tenella ◽

Single Test ◽

Normal Parent ◽

Twofold Increase ◽

Development Of Resistance ◽

Resistant Strains

A twofold increase in resistance to glycarbylamide was induced in a strain of Eimeria tenella in chicks. This strain remained susceptible to amprolium, nicarbazin, nitrofurazone, zoalene, 3,5-dinitrobenzamide, 2-chloro-4-nitrobenzamide (M & B 5921) and spiramycin.At least an eightfold resistance to 2-chloro-4-nitrobenzamide (M & B 5921) was developed in another strain of E. tenella. This strain was also resistant to nitrofurazone, zoalene and 3,5-dinitrobenzamide, but not to glycarbylamide, amprolium, nicarbazin and spiramycin.A single test showed no transfer of drug-resistance when the two resistant strains were given simultaneously to the same birds.When a small number of parasites of a glycarbylamide-resistant strain of E. tenella was introduced into a larger inoculum of the normal parent strain, the resistant individuals appeared to diminish in number during passages through untreated chicks.I wish to thank Mrs B. M. Mitchell, Miss C. A. Hitchcock and Miss J. Watkins for technical assistance at various stages of the work.

Download Full-text