[
Int J Parasitol,
1994]
An absolute pre-requisite for a genetic response to a selective pressure is genetic variation within the population under selection. Helminth populations are clearly able to respond to selective pressures and must, therefore, be genetically heterogeneous. While not quite tautological, this is at best indirect evidence for the existence of genetic variation but there are few examples of well documented helminth phenotypic variation with a proven genetic basis. Isozyme analysis has provided more direct evidence for variation but attempts to link this variation to responses to selection or to identify the forces maintaining that variation have been largely unsuccessful. Thus there is a clear need for new techniques. The recent application of PCR and direct sequencing technology to the study of helminth genetics has allowed the genotypes of individual worms to be determined and the first direct measurements of allele frequencies to be made in this group of organisms. In addition, the application of genetic and molecular data from Caenorhabditis elegans is a potentially rich source of new markers. These techniques do not require that the genetic basis of the phenotype in question be known since a large number of loci can be examined and selection detected through changes in the frequency of anonymous linked marker loci. Phenotypes with complex genetic bases can, therefore, be analysed. I have applied these techniques to the study of anthelmintic resistance genetics and others have applied them to the genetics of inhibited development in Ostertagia. Other phenotypes that are of great interest are the potential for selection of resistance to vaccination and the use of genetically resistant hosts. The ease with which helminths have countered all classes of anthelminitics and the apparently high levels of polymorphism in helminth populations suggest that immunological control methods may also prove to be vulnerable to the adaptive capabilities of the parasite. Evidence from a mouse-helminth model system has already provided evidence that worms can meet the challenge.
[
Int J Parasitol,
2003]
The sugar trehalose is claimed to be important in the physiology of nematodes where it may function in sugar transport, energy storage and protection against environmental stresses. In this study we investigated the role of trehalose metabolism in nematodes, using Caenorhabditis elegans as a model, and also identified complementary DNA clones putatively encoding genes involved in trehalose pathways in filarial nematodes. In C. elegans two putative trehalose-6-phosphate synthase (tps) genes encode the enzymes that catalyse trehalose synthesis and five putative trehalase (tre) genes encode enzymes catalysing hydrolysis of the sugar. We showed by RT-PCR or Northern analysis that each of these genes is expressed as mRNA at all stages of the C. elegans life cycle. Database searches and sequencing of expressed sequence tag clones revealed that at least one tps gene and two tre genes are expressed in the filarial nematode Brugia malayi, while one tps gene and at least one tre gene were identified for Onchocerca volvulus. We used the feeding method of RNA interference in C. elegans to knock down temporarily the expression of each of the tps and tre genes. Semiquantitative RT-PCR analysis confirmed that expression of each gene was silenced by RNA interference. We did not observe an obvious phenotype for any of the genes silenced individually but gas-chromatographic analysis showed >90% decline in trehalose levels when both tps genes were targeted simultaneously. This decline in trehalose content did not affect viability or development of the nematodes.
[
Front Genet,
2019]
Onchocerciasis and lymphatic filariasis are targeted for elimination, primarily using mass drug administration at the country and community levels. Elimination of transmission is the onchocerciasis target and global elimination as a public health problem is the end point for lymphatic filariasis. Where program duration, treatment coverage, and compliance are sufficiently high, elimination is achievable for both parasites within defined geographic areas. However, transmission has re-emerged after apparent elimination in some areas, and in others has continued despite years of mass drug treatment. A critical question is whether this re-emergence and/or persistence of transmission is due to persistence of local parasites-i.e., the result of insufficient duration or drug coverage, poor parasite response to the drugs, or inadequate methods of assessment and/or criteria for determining when to stop treatment-or due to re-introduction of parasites <i>via</i> human or vector movement from another endemic area. We review recent genetics-based research exploring these questions in <i>Onchocerca volvulus</i>, the filarial nematode that causes onchocerciasis, and <i>Wuchereria bancrofti</i>, the major pathogen for lymphatic filariasis. We focus in particular on the combination of genomic epidemiology and genome-wide associations to delineate transmission zones and distinguish between local and introduced parasites as the source of resurgence or continuing transmission, and to identify genetic markers associated with parasite response to chemotherapy. Our ultimate goal is to assist elimination efforts by developing easy-to-use tools that incorporate genetic information about transmission and drug response for more effective mass drug distribution, surveillance strategies, and decisions on when to stop interventions to improve sustainability of elimination.