Drug Resistance in Eimeria tenella. VIII. The Influence of Quinacrine Hydrochloride on Development of Resistance to Glycarbylamide

1969 ◽  
Vol 55 (1) ◽  
pp. 208 ◽  
Author(s):  
D. K. McLoughlin ◽  
J. L. Gardiner
Keyword(s):  
Drug Resistance ◽  
Eimeria Tenella ◽  
Development Of Resistance

Eimeria tenella in chickens: development of resistance to quinolone anticoccidial drugs

Parasitology ◽  
1975 ◽  
Vol 71 (1) ◽  
pp. 41-49 ◽  
Author(s):  
H. D. Chapman
Keyword(s):  
Drug Resistance ◽  
Weight Gain ◽  
Liquid Nitrogen ◽  
Selection Pressure ◽  
Drug Tolerance ◽  
Eimeria Tenella ◽  
Cross Resistance ◽  
Drug Selection ◽  
Laboratory Conditions ◽  
Development Of Resistance

The development of drug resistance by the present Houghton strain of Eimeria tenella to the quinolones, methyl benzoquate and buquinolate, was found to take place after a single experimental passage. The development of resistance was independent of drug selection pressure and showed cross resistance to other quinolones, but not to amprolium and robenidine. When the Weybridge, Beltsville and Elberfeld strains of E. tenella were compared under similar laboratory conditions, the Weybridge and Elberfeld strains developed resistance to methyl benzoquate after 6 passages and the Beltsville after 5. Studies on the response of the Houghton strain to methyl benzoquate and buquinolate revealed that the drugs did not completely control the infection as measured by weight gain and that oocyst production was not suppressed. These observations indicate that the strain had already acquired some resistance to these drugs. This was confirmed by examining the resistance to methyl benzoquate of a culture of the Houghton strain of E. tenella which had been stored frozen in liquid nitrogen since 1969. This showed full sensitivity to the drug and developed resistance after 8 passages. This suggests that drug tolerance has been acquired by the Houghton strain since 1969.Oocyst lines were established from the Houghton strain by infecting single birds with approximately 10 oocysts. Eleven of these lines were found to be sensitive to methyl benzoquate, and nine to give rise to resistant parasites. It is concluded that the Houghton strain is contaminated by a small number of resistant oocysts which can be eliminated from a culture by dilution of the challenge inoculum. One of these Houghton oocyst lines, sensitive to methyl benzoquate, developed resistance after 8 serial passages.

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

Parasitology ◽  
1966 ◽  
Vol 56 (1) ◽  
pp. 25-37 ◽  
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.

Eimeria tenella: experimental studies on the development of resistance to robenidine

Parasitology ◽  
1976 ◽  
Vol 73 (3) ◽  
pp. 265-273 ◽  
Author(s):  
H. D. Chapman
Keyword(s):  
Drug Resistance ◽  
Selection Pressure ◽  
Experimental Studies ◽  
Eimeria Tenella ◽  
Parasite Population ◽  
Cross Resistance ◽  
Drug Selection ◽  
Development Of Resistance

The development of resistance by the Houghton strain (H) of E. tenella to robenidine has been studied, in the laboratory, by serially passaging the strain in chickens fed increasing concentrations of drug. Resistance to robenidine developed more readily in experiments using larger numbers of birds with higher numbers of oocysts in the inoculum. Both these factors increased the parasite population and increased the chance of selecting parasites resistant to the drug. E. tenella (H) was made resistant to 264 ppm robenidine and showed no cross-resistance to other anticoccidial agents. Resistance arose in a series of ‘steps’ as the concentration of drug was increased. E. tenella (H) was continuously passaged at concentrations ranging from 2 to 33 ppm of robenidine. After 16 passages, lines passaged at 2, 4 and 8 ppm were not resistant to 33 ppm robenidine, suggesting that the degree of resistance developed was dependent upon the drug selection pressure.

Coumarin-1,2,3-triazole Hybrid Molecules: An Emerging Scaffold for Combating Drug Resistance

2021 ◽  
Vol 21 ◽  
Author(s):  
Harish C. Upadhyay
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Agents ◽  
Plant Secondary Metabolites ◽  
Cost Effective ◽  
Resistance Mechanisms ◽  
Biologically Active ◽  
Multidrug Therapy ◽  
Diverse Range ◽  
Development Of Resistance ◽  
Hybrid Molecules

: No doubt antibiotics have saved billions of lives, but lack of novel antibiotics, development of resistance mechanisms in almost all clinical isolates of bacteria, and recurrent infections caused by persistent bacteria hamper the successful treatment of infections. Due to widespread emergence of resistance, even the new families of antimicrobial agents have a short life expectancy. Drugs acting on single target often lead to drug resistance and are associated with various side effects. To overcome this problem either multidrug therapy or single drug acting on multiple targets may be used. The later are called ‘hybrid molecules’ which are formed by clubbing two biologically active pharmacophores together with or without an appropriate linker. In this rapidly evolving era, the development of natural product-based hybrid molecules may be a super-alternative to multidrug therapy to combat drug resistance caused by various bacterial and fungal strains. Coumarins (benzopyran-2-one) are one of the earliest reported plant secondary metabolites having clinically proven diverse range of pharmacological properties. On the other hand, 1,2,3-triazole is a common pharmacophore in many drugs responsible for polar interactions improving the solubility and binding affinity to biomolecular targets. In this review we discuss recent advances in Coumarin-1,2,3-triazole hybrids as potential antibacterial agents aiming to provide a useful platform for the exploration of new leads with broader spectrum, more effectiveness, less toxicity with multiple modes of action for the development of cost-effective and safer drugs in the future.

scholarly journals Machine-learning reveals that Mycobacterium tuberculosis genotypes and anatomic disease site impacts drug resistance and disease transmission among patients with proven extra-pulmonary tuberculosis

2020 ◽  
Author(s):  
Doctor Busizwe Sibandze ◽  
Beki Themba Magazi ◽  
Lesibana Anthony Malinga ◽  
Nontuthuko Excellent Maningi ◽  
Bong Akee Shey ◽  
...  
Keyword(s):  
Machine Learning ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Disease Transmission ◽  
East Asian ◽  
Extrapulmonary Tuberculosis ◽  
Machine Learning Algorithms ◽  
East African ◽  
Development Of Resistance ◽  
Asian Lineage

Abstract Background: There is a general dearth of information on extrapulmonary tuberculosis (EPTB). Here, we investigated Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane metropolitan area, in South Africa.Methods: Consecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. MTBDRplus assay was used to search mutations for isoniazid and rifampin resistance. Machine learning algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and corresponding 95% confidence intervals (CI). Results: Of the 70 isolates examined, the largest cluster comprised 25 (36%) Mtb strains that belonged to the East Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when compared to the Euro-American and East-African Indian lineages: OR= 10.11 (95% CI: 1.56-116). Lymphadenitis, meningitis and cutaneous TB, were significantly more likely to be associated with drug resistance: OR=12.69 (95% CI: 1.82-141.60) and AR = 0.25 (95% CI: 0.06-0.43) when compared with other EPTB sites, which suggests that poor rifampin penetration might be a contributing factor.Conclusions: The majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the development of resistance.

scholarly journals Anticoccidial activity of Artemisinin and Extract of Artemesia annua leaves in chicken infected by Eimeria tenella

2018 ◽  
Vol 22 (4) ◽  
pp. 196 ◽  
Author(s):  
Ening Wiedosari ◽  
April Hari Wardhana
Keyword(s):  
Drug Resistance ◽  
Body Weight ◽  
Normal Level ◽  
Group Treatment ◽  
Packed Cell Volume ◽  
Eimeria Tenella ◽  
Lesion Score ◽  
Safe Alternative ◽  
Anticoccidial Activity ◽  
Continuous Use

<p>The continuous use of anticoccidial drug in chicken often continuously generates drug resistance and tissue residue; so thatconsequently, a safe alternative anticoccidial drug based on herb is fundamentally required. The aim of thise study was to examine anticcocidial activity of artemisinin and extract of Artemesia annua leaves in chicken infected by Eimeria tenella. A total of 35 chickens of Cobb strain was divided into seven groups with five replicates birds per group, i.e. uninfected chicken group (P I), infected but untreated chicken group (P II), infected and treated chicken group with 8.5 ppm, 17 ppm, 34 ppm, for P III, P IV and P V respectively, infected and treated chicken with 17 ppm of A. annua extract (P VI) and infected and treated chicken with Sulfa (P VII). All chicken, except the uninfected group, whereas infected with 2000 infective oocyst of E. tenella except the uninfected group. Treatment was delivered by oral, once per day for eight days. The criteria observed were clinical manifestation of chickens, number of oocyst in feces, body weight, cecal lesion score, haematocrit (packed cell volume) and haemoglobin value. The results showed that extract of A. annua leaves (P VI) was the most effective treatment to reduce the number of oocyst in feces (74.18%), followed by 34 ppm of artemisinin group (P VII). In addition, application of A. annua extract and artemisinin was significantly able to decreased the cecal lesion score (P&lt;0.05). Even though body weight and Hb value were not indifferent significantly different (p&gt;0.05), however A. annua extract and artemisinin treatments were significantly able to hold PCV value on normal level compared to P II and P IV (P&lt;0.05). It concluded that extract A. annua leaves and artemisinin could be used an alternative anticoccidial in chickens.</p>

scholarly journals Targeting CDC7 sensitizes resistance melanoma cells to BRAFV600E-specific inhibitor by blocking the CDC7/MCM2-7 pathway

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shaimaa A. Gad ◽  
Hamdy E. A. Ali ◽  
Rofaida Gaballa ◽  
Rania M. Abdelsalam ◽  
Mourad Zerfaoui ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Metastatic Melanoma ◽  
Clinical Effect ◽  
Specific Inhibitor ◽  
Melanoma Cells ◽  
Development Of Resistance ◽  
Dual Targeting ◽  
Low Concentrations ◽  
Resistant Cells

Abstract Although the utilization of selective BRAFV600E inhibitors is associated with improved overall survival in patients with metastatic melanoma, a growing challenge of drug resistance has  emerged. CDC7 has been shown to be overexpressed and associated with poor prognosis in various cancers including melanoma. Thus, we aimed to elucidate the biological role of CDC7 in promoting Vemurafenib resistance and the anticipated benefits of dual targeting of BRAFV600E and CDC7 in melanoma cells. We performed exosomes-associated microRNA profiling and functional assays to determine the role of CDC7 in drug resistance using Vemurafenib-sensitive and resistant melanoma cells. Our results demonstrated that Vemurafenib-resistant cells exhibited a persistent expression of CDC7 in addition to prolonged activity of MCM2 compared to drug-sensitive cells. Reconstitution of miR-3613-3p in resistant cells downregulated CDC7 expression and reduced the number of colonies. Treatment of cells with low concentrations of CDC7 inhibitor TAK-931 sensitized resistant cells to Vemurafenib and reduced the number of cell colonies. Taken together, CDC7 overexpression and downregulation of miR-3613-3p were associated with Vemurafenib resistance in BRAFV600E- bearing melanoma cells. Dual targeting of CDC7 and BRAFV600E reduced the development of resistance against Vemurafenib. Further studies are warranted to investigate the clinical effect of targeting CDC7 in metastatic melanoma.

The development of resistance to metachloridine inPlasmodium gallinaceumin Chicks

Parasitology ◽  
1953 ◽  
Vol 42 (3-4) ◽  
pp. 277-286 ◽  
Author(s):  
Ann Bishop ◽  
Elspeth W. McConnachie
Keyword(s):  
Growth Rate ◽  
Drug Resistance ◽  
Normal Population ◽  
Rapid Development ◽  
Cross Resistance ◽  
Development Of Resistance ◽  
The Gift ◽  
Higher Doses ◽  
Resistance Tests ◽  
Selection Of

1. An increase in resistance to metachloridine of more than 100-fold was obtained within a few weeks in a strain ofPlasmodium gallinaceumtreated with gradually increasing doses of the drug and maintained in young chicks by blood-inoculation at intervals of 2–3 days.2. There was no evidence that the rapid development of resistance arose by the selection of highly resistant individuals present in the normal population.3. Two strains ofP. gallinaceumpassaged through chicks treated with 0·025 mg. doses of the drug gradually became resistant to greater concentrations than that to which they had been exposed, though their growth rate decreased when they were inoculated into birds receiving higher doses of the drug.4. In both strains maintained in birds treated with 0·025 mg. doses of the drug, resistance reached a maximum beyond which it did not increase.5. Cross-resistance tests failed to show any relationship in mode of action between meta-chloridine and pamaquin, mepacrine, quinine or chloroquine. A strain ofP. gallinaceum, highly resistant to metachloridine, showed slight resistance to sulphadiazine, sulphapyridine and sulphathiazole, but none to sulphanilamide or proguanil.We are indebted to the Cyanamid Products Ltd., London, for the gift of the Folvite used in these experiments.

scholarly journals Role of embB Codon 306 Mutations in Mycobacterium tuberculosis Revisited: a Novel Association with Broad Drug Resistance and IS6110 Clustering Rather than Ethambutol Resistance

2005 ◽  
Vol 49 (9) ◽  
pp. 3794-3802 ◽  
Author(s):  
Manzour Hernando Hazbón ◽  
Miriam Bobadilla del Valle ◽  
Marta Inírida Guerrero ◽  
Mandira Varma-Basil ◽  
Ingrid Filliol ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Odds Ratio ◽  
Univariate Analysis ◽  
Drug Susceptibility ◽  
Drug Resistant ◽  
Development Of Resistance ◽  
Resistance Patterns ◽  
Novel Association

ABSTRACT Mutations at position 306 of embB (embB306) have been proposed as a marker for ethambutol resistance in Mycobacterium tuberculosis; however, recent reports of embB306 mutations in ethambutol-susceptible isolates caused us to question the biological role of this mutation. We tested 1,020 clinical M. tuberculosis isolates with different drug susceptibility patterns and of different geographical origins for associations between embB306 mutations, drug resistance patterns, and major genetic group. One hundred isolates (10%) contained a mutation in embB306; however, only 55 of these mutants were ethambutol resistant. Mutations in embB306 could not be uniquely associated with any particular type of drug resistance and were found in all three major genetic groups. A striking association was observed between these mutations and resistance to any drug (P < 0.001), and the association between embB306 mutations and resistance to increasing numbers of drugs was highly significant (P < 0.001 for trend). We examined the association between embB306 mutations and IS6110 clustering (as a proxy for transmission) among all drug-resistant isolates. Mutations in embB306 were significantly associated with clustering by univariate analysis (odds ratio, 2.44; P = 0.004). In a multivariate model that also included mutations in katG315, katG463, gyrA95, and kasA269, only mutations in embB306 (odds ratio, 2.14; P = 0.008) and katG315 (odds ratio, 1.99; P = 0.015) were found to be independently associated with clustering. In conclusion, embB306 mutations do not cause classical ethambutol resistance but may predispose M. tuberculosis isolates to the development of resistance to increasing numbers of antibiotics and may increase the ability of drug-resistant isolates to be transmitted between subjects.

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