Turnover of the surface proteins of adult and third and fourth stage larval Brugia pahangi

Marshall, Elizabeth; Howells, R. E.

doi:10.1016/0166-6851(86)90046-0

Cited by 20 publications

(3 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Early studies reported that adult surfaces appeared to be quite stable with limited protein shedding (Marshall and Howells, 1986, Scott et al., 1988), but later work suggested that small amounts of surface proteins are released, albeit slowly (Devaney, 1988, Kwan–Lim et al., 1989, Maizels et al., 1989). Given that filariae are long-lived parasites, some rate of turnover of cuticle proteins is expected to occur, and the inhibition of this process by FLBZ could lead to slow death of the worm.…”

Section: Discussionmentioning

confidence: 99%

Profiling the macrofilaricidal effects of flubendazole on adult female Brugia malayi using RNAseq

O’Neill

Ballesteros

Tritten

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

View full text Add to dashboard Cite

The use of microfilaricidal drugs for the control of onchocerciasis and lymphatic filariasis (LF) necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be enhanced by the availability of a macrofilaricidal drug. Flubendazole (FLBZ), a benzimidazole anthelmintic, is an appealing candidate. FLBZ has demonstrated potent macrofilaricidal effects in a number of experimental rodent models and in one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass drug administration campaigns due to its limited oral bioavailability. A new formulation that enables sufficient bioavailability following oral administration could render FLBZ an effective treatment for onchocerciasis and LF. Identification of drug-derived effects is important in ascertaining a dosage regimen which is predicted to be lethal to the parasite in situ. In previous histological studies, exposure to FLBZ induced damage to tissues required for reproduction and survival at pharmacologically relevant concentrations. However, more precise and quantitative indices of drug effects are needed. This study assessed drug effects using a transcriptomic approach to confirm effects observed histologically and to identify genes which were differentially expressed in treated adult female Brugia malayi. Comparative analysis across different concentrations (1 μM and 5 μM) and durations (48 and 120 h) provided an overview of the processes which are affected by FLBZ exposure. Genes with dysregulated expression were consistent with the reproductive effects observed via histology in our previous studies. This study revealed transcriptional changes in genes involved in embryo development. Additionally, significant downregulation was observed in genes encoding cuticle components, which may reflect changes in developing embryos, the adult worm cuticle or both. These data support the hypothesis that FLBZ acts predominantly on rapidly dividing cells, and provides a basis for selecting molecular markers of drug-induced damage which may be of use in predicting efficacious FLBZ regimens.

show abstract

Section: Discussionmentioning

confidence: 99%

Profiling the macrofilaricidal effects of flubendazole on adult female Brugia malayi using RNAseq

O’Neill

Ballesteros

Tritten

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

View full text Add to dashboard Cite

show abstract

“…The dynamic nature of the cuticular surface of infective-stage larvae (L3) has also been observed for filarial parasites. After labelling surface components with 12 'T, Brugia pahangi L3s lost over 90 °0 of the labelled molecules over an 8-day developmental period in vivo (Marshall & Howells, 1986). In in vitro experiments with B. malayi L3s, an anti-S. malayi monoclonal IgM directed against one of the surface constituents of the infective-stage larvae of this species was shed rapidly from the surface of parasites (Carlow et al 1987).…”

Section: Introductionmentioning

confidence: 99%

Antigen shedding from the surface of the infective stage larvae ofDirofilaria immitis

et al. 1989

View full text Add to dashboard Cite

A qualitative and quantitative analysis was made of the release of surface-associated molecules from developing Dirofilaria immitis infective-stage larvae (L3). D. immitis L3s were labelled with 125I using an Iodogen catalysed reaction and either maintained in culture or placed in chambers that were implanted into Lewis rats. The larvae released 10-20% of the labelled material each day during the first 4 days of in vitro and in vivo development. The loss of surface-labelled peptides from developing larvae corresponded with an increase in the amount of trichloroacetic acid-precipitable radioactivity found in the culture medium. SDS-PAGE analysis of the labelled material showed that the same 35 and 6 kDa components found in larval extracts were shed into culture medium by the developing parasites. Metabolic labelling studies and experiments in which larvae were labelled after different times in culture indicated that, once released, the surface-associated molecules were not replaced, and that this net loss of surface peptides resulted in a reduction in the antigenic potential of the cuticular surface. Antibodies from both immunized rabbits and naturally infected dogs immunoprecipitated the 35 kDa component. In contrast, the 6 kDa molecule was not recognized by the antibodies in any of the sera tested. Shedding of surface peptides and reducing surface antigenicity may represent mechanisms by which D. immitis infective-stage larvae evade immune attack.

show abstract

“…However, the evidence for turnover of surface components of filarial nematode is scarce (Marshall and Howells, 1986;Howells and Blainley, 1983).…”

Section: Introductionmentioning

confidence: 99%

Surface lectin binding characteristics of developing stages of Brugia in Armigeres subalbatus: I. Brugia pahangi.

Zahedi

Denham

Ham

1990

Jap. J. Trop. Med. Hyg.

View full text Add to dashboard Cite

Abstract:Surface characteristics of microfilariae and developing stages of Brugia pahangi in its natural vector, Armigeres subalbatus were assayed using fluorescein isothiocynate conjugated lectins. The following lectins were used: wheat germ agglutinins, lentil agglutinins, Helix aspersa agglutinins, Concanavalin A agglutinins, kidney bean agglutinins, asparagus pea agglutinins and pea nut agglutinins. It was observed that developing stages of B. pahangi the mosquito showed a dynamic surface carbohydrate characteristics.The larvae change their surface coat configuration frequently during the 10 day observation period. However, blood dwelling microfilariae and fully matured infective larvae obtained from the mosquito's head showed little or no binding affinity for the lectins tested. It's postulated that the rapid turnover of the surface carbohydrates, while development of the larvae is taking place, is the worm's response to a 'hostile' mosquito environment.

show abstract

Turnover of the surface proteins of adult and third and fourth stage larval Brugia pahangi

Cited by 20 publications

References 10 publications

Profiling the macrofilaricidal effects of flubendazole on adult female Brugia malayi using RNAseq

Profiling the macrofilaricidal effects of flubendazole on adult female Brugia malayi using RNAseq

Antigen shedding from the surface of the infective stage larvae ofDirofilaria immitis

Surface lectin binding characteristics of developing stages of Brugia in Armigeres subalbatus: I. Brugia pahangi.

Contact Info

Product

Resources

About