RESUMEN
The economic impact of gastrointestinal (GI) nematode infections on livestock production is well documented worldwide. Increasing evidence supports the hypothesis that parasite colonization induces significant changes in the GI tract environment and, therefore, in the landscape where the microbiota and parasites occur. Understanding the interactions between bacterial and parasite populations in the digestive tract of livestock may be useful to design parasite control strategies based on microbiota modification. The aims of this work were to investigate the impact of the oxytetracycline-mediated manipulation of the gut microbial community on the composition of GI nematode populations in naturally infected sheep and to explore changes in the GI microbial communities after nematode population treatment with the anthelmintic compound monepantel. Extensive manipulation of the GI microbiota with a therapeutic dose of the long-acting oxytetracycline formulation did not induce significant changes in the GI nematode burden. The gut microbiota of treated animals returned to control levels 17 days after treatment, suggesting strong resilience of the sheep microbial community to antibiotic-mediated microbiota perturbation. A significant decrease of the bacterial Mycoplasmataceae family (Log2FC = -4, Padj = 0.001) and a marked increase of the Methanobacteriaceae family (Log2FC = 2.9, Padj = 0.018) were observed in the abomasum of sheep receiving the monepantel treatment. While a comprehensive evaluation of the interactions among GI mycoplasma, methanobacteria and nematode populations deserves further assessment, the bacteria-nematode population interactions should be included in future control programs in livestock production. Understanding how bacteria and parasites may influence each other in the GI tract environment may substantially contribute to the knowledge of the role of microbiota composition in nematode parasite establishment and the role of the parasites in the microbiota composition.
Asunto(s)
Microbioma Gastrointestinal , Tracto Gastrointestinal , Nematodos , Infecciones por Nematodos , Oxitetraciclina , Enfermedades de las Ovejas , Animales , Ovinos/parasitología , Ovinos/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedades de las Ovejas/parasitología , Enfermedades de las Ovejas/microbiología , Enfermedades de las Ovejas/tratamiento farmacológico , Infecciones por Nematodos/veterinaria , Infecciones por Nematodos/tratamiento farmacológico , Infecciones por Nematodos/parasitología , Infecciones por Nematodos/microbiología , Nematodos/microbiología , Nematodos/efectos de los fármacos , Nematodos/fisiología , Oxitetraciclina/farmacología , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/parasitología , Aminoacetonitrilo/análogos & derivados , Aminoacetonitrilo/farmacología , Bacterias/efectos de los fármacosRESUMEN
BACKGROUND: Haemonchus contortus, a gastrointestinal nematode parasite of sheep, is mainly controlled by anthelmintics; the occurrence of anthelmintic resistance leads to treatment failures and increases economic burden. Because molecular mechanisms involved in drug resistance can be elucidated by genomic studies, an extreme quantitative trait locus (X-QTL) mapping approach was used to identify co-segregation of the resistance phenotype with genetic markers to detect the genome-wide variants associated with monepantel resistance in H. contortus. METHODS: A cross between H. contortus isolates using parental susceptible (Par-S) males and monepantel resistant (Par-R) females resulted in SR progeny, while reciprocal cross resulted in RS progeny. Pools (n = 30,000) of infective larvae (L3) recovered from Par-R, and from SR and RS populations in the F3 generation, collected both before (unselected group) and 7 days after (selected group) selection with monepantel treatment in sheep hosts, were subjected to genome sequencing (Pool-Seq). Pairwise comparisons of allele frequencies between unselected and selected groups were performed for each population by Fisher's exact test (FET) and for both populations combined by a Cochran-Mantel-Haenszel (CMH) test. RESULTS: Mapping rates varied from 80.29 to 81.77% at a 90.4X mean coverage of aligned reads. After correction for multiple testing, significant (P < 0.05) changes in allele frequencies were detected by FET for 6 and 57 single nucleotide polymorphisms (SNPs) in the SR and RS populations, respectively, and by the CMH test for 124 SNPs in both populations. The significant variants located on chromosome 2 generated a selection signal in a genomic region harboring the mptl-1, deg-3 and des-2 genes, previously reported as candidates for monepantel resistance. In addition, three new variants were identified in the mptl-1 gene. CONCLUSIONS: This study expands knowledge on genome-wide molecular events underlying H. contortus resistance to monepantel. The identification of a genome region harboring major genes previously associated with monepantel resistance supports the results of the employed X-QTL approach. In addition, a deletion in exon 11 of the mptl-1 gene should be further investigated as the putative causal mutation leading to monepantel resistance.
Asunto(s)
Aminoacetonitrilo/análogos & derivados , Antihelmínticos/farmacología , Resistencia a Medicamentos/genética , Haemonchus/efectos de los fármacos , Haemonchus/genética , Sitios de Carácter Cuantitativo , Aminoacetonitrilo/farmacología , Animales , Femenino , Variación Genética , Masculino , Mutación , FenotipoRESUMEN
Multiple drug resistance of nematodes against anthelmintics has become one of the most important economic problems in sheep production worldwide. The aim of this experiment was to evaluate the efficacy of monepantel (2.5mg/kg) against gastrointestinal nematodes in fecal egg count reduction test (FECRT) and controlled efficacy test (CT) in naturally infected sheep. We used 30 sheep for the FECRT and 20 sheep for the CT, equally divided into control and treated groups. In the FECRT, the reduction was 98%. Larval identification of pre-treatment coprocultures revealed 100% Haemonchus spp. for both control and treated groups. Post-treatment culture of treated sheep was 100% Oesophagostomum spp., but only few larvae were recovered. In the control group, they were 99% Haemonchus spp and 1% Oesophagostomum spp. larvae. Based on the FECRT, Haemonchus spp. was considered susceptible to monepantel. The efficacy of monepantel in the CT against Haemonchus contortus and Trichostrongylus axei was 100% and against Cooperia curticei was 99.7%. For Trichostrongylus colubriformis, the efficacy was -21.5%. In both treated and untreated animals, Oesophagostomum columbianum was recovered from the large intestines. Based on FECRT and CT and in accordance with WAAVP standards, monepantel was ineffective against T. colubriformis and O. columbianum, but effective against H. contortus, T. axei and C. curticei in the studied flock.
Asunto(s)
Aminoacetonitrilo/análogos & derivados , Antinematodos/uso terapéutico , Enfermedades de las Ovejas/tratamiento farmacológico , Tricostrongiliasis/veterinaria , Trichostrongylus/efectos de los fármacos , Abomaso/parasitología , Administración Oral , Aminoacetonitrilo/administración & dosificación , Aminoacetonitrilo/farmacología , Aminoacetonitrilo/uso terapéutico , Animales , Antinematodos/administración & dosificación , Antinematodos/farmacología , Brasil , Resistencia a Medicamentos , Heces/parasitología , Femenino , Haemonchus/efectos de los fármacos , Intestinos/parasitología , Masculino , Oesophagostomum/efectos de los fármacos , Ovinos , Enfermedades de las Ovejas/parasitología , Trichostrongyloidea/efectos de los fármacos , Tricostrongiliasis/tratamiento farmacológicoRESUMEN
Foi estudado o efeito do aminoacetonitrila, administrado durante o período degestaçäo, sobre o desenvolvimento dos germes dentais do camundongo. Os animais foram sacrificados a 1, 3 8 e 10 dias após o nascimento. Verificou-se que o aminoacetonitrila retarda o desenvolvimento dos germes dentais, porém, näo de maneira irreversível, uma vez que há uma recuperaçäo da fase de desenvolvimento