Immunoreactive molecules of Brugia malayi and their diagnostic potential

Singh, Usha; Misra, S. S.; Murthy, P. K.; Katiyar, J. C.; Agrawal, Ajay; Sircar, A. R.

doi:10.1016/s0888-0786(96)01081-5

Cited by 32 publications

(26 citation statements)

References 11 publications

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“…The sub-periodic strain of B. malayi was maintained in the rodent M. coucha through cyclical transmission by the vector Aedes aegypti (Singh et al 1997). Briefly, mosquitoes fed on 1% glucose solution were infected by feeding on the blood of a heavily microfilaremic donor Mastomys.…”

Section: Infectionmentioning

confidence: 99%

4-Methyl-7-(tetradecanoyl)-2H-1-benzopyran-2-one: a novel DNA topoisomerase II inhibitor with adulticidal and embryostatic activity against sub-periodic Brugia malayi

Misra‐Bhattacharya

Katiyar

Bajpai

et al. 2004

Parasitology Research

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A compound of the coumarin class, 4-methyl-7-(tetradecanoyl)-2H-1-benzopyran-2-one, was evaluated for antifilarial activity against the human filarial parasite, Brugia malayi (sub-periodic strain) in Mastomys coucha. The test compound brought about a 24.4% reduction in circulating microfilaremia on day 8 after initiation of treatment when administered by the peritoneal route at a dose of 50 mg/kg for 5 consecutive days. The compound also caused a 62.0% mortality in adult parasites. Apart from killing adult filariids, it also brought about sterilization of 81.8% of the surviving female B. malayi. An oral dose of 200 mg/kg for 5 consecutive days was less effective (35.5% adulticidal efficacy and 65.8% sterilization). In vitro, the compound killed adult B. malayi at 100 microM concentration and inhibited DNA topoisomerase II activity in the filarial parasite. Studies are in progress using the compound in combination with standard antifilarials as well as other active agents.

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Section: Infectionmentioning

confidence: 99%

4-Methyl-7-(tetradecanoyl)-2H-1-benzopyran-2-one: a novel DNA topoisomerase II inhibitor with adulticidal and embryostatic activity against sub-periodic Brugia malayi

Misra‐Bhattacharya

Katiyar

Bajpai

et al. 2004

Parasitology Research

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“…Freedman et al (1989) identified the *43 kDa molecule of B. malayi L 3 to be reactive with endemic normals and suggested that this molecule may have prophylactic potential. However, Singh et al (1997) reported that the *43 kDa compound of all three life stages of B. malayi (MF, L 3 , and adult worms) was reactive with MF-positive subjects. Since the *45 kDa molecule identified in the present study was from B. malayi, which is closely related to W. bancrofti (a human lymphatic-dwelling parasite) we expected that it might have protective potential, but surprisingly this was not observed in the present study.…”

Section: Discussionmentioning

confidence: 97%

Identification of Brugia malayi adult worm molecules immunoreactive with sera of infected animals treated with antifilarial and re-infected with homologous infection and their role in the establishment of infection in Mastomys coucha

et al. 2007

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The present study was aimed at identifying molecules of Brugia malayi adult worm (BmA) that are immunoreactive with sera of B. malayi-infected Mastomys coucha treated with albendazole (ALB) or diethylcarbamazine (DEC) and reexposed to infection and the effect of immunization with the molecules on the establishment of infection in M. coucha. A *62 kDa molecule showed strong reactivity with sera of infected ALB-treated reinfected animals whereas *32 kDa and *45 kDa molecules strongly reacted with sera of DEC-treated reinfected animals. Two molecules (*22 kDa and *28 kDa) reacted with sera of infected untreated and reinfected control animals. Immunization with *62 kDa molecules reduced the adult worm recovery by 58% (P \ 0.001) and microfilaremia by 32-54% (P \ 0.05-0.01) of unimmunized controls. Animals immunized with the *32 kDa molecule exhibited 63% recovery of adult worms with no effect on circulating microfilaraemia. L 3 inoculation in *62 kDa-immunized animals upregulated cellular proliferation, interferon-c (IFN-c) and IgG responses (P \ 0.001) but downregulated interleukin-10 (IL-10) response (P \ 0.001). Animals immunized with *22, *28, *32 and *45 kDa molecules and bearing L 3 -induced infection showed mixed responses. Lymph node cells of unimmunized animals exposed to *28, *32 and *62 kDa molecules showed significant DNA damage (P \ 0.001) as compared to untreated control; *62 kDa molecule induced maximum damage. In conclusion, immunization with a *62 kDa molecule suppressed the establishment of L 3 -induced infection in M. coucha and this correlated with enhanced cellular proliferation and IFN-c release, downregulation of IL-10, increased levels and DNA damage in lymph node cells.

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“…Mastomys were infected by s.c. inoculation of 100 infective larvae (L3) recovered from A. aegypti mosquitoes fed on donor mastomys 8 or 9 days earlier, as described previously (44). Animals were monitored for microfilaremia in 10 l tail blood at between 12:00 and 12:45 h starting from day 90 onwards (completion of the incubation period).…”

Section: Methodsmentioning

confidence: 99%

Molecular Characterization of an rsmD -Like rRNA Methyltransferase from the Wolbachia Endosymbiont of Brugia malayi and Antifilarial Activity of Specific Inhibitors of the Enzyme

Rana

Chandra

Siddiqi

et al. 2013

Antimicrob Agents Chemother

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bThe endosymbiotic organism Wolbachia is an attractive antifilarial drug target. Here we report on the cloning and expression of an rsmD-like rRNA methyltransferase from the Wolbachia endosymbiont of Brugia malayi, its molecular properties, and assays for specific inhibitors. The gene was found to be expressed in all the major life stages of B. malayi. The purified enzyme expressed in Escherichia coli was found to be in monomer form in its native state. The activities of the specific inhibitors (heteroaryl compounds) against the enzyme were tested with B. malayi adult and microfilariae for 7 days in vitro at various concentrations, and NSC-659390 proved to be the most potent compound (50% inhibitory concentration [IC 50 ], 0.32 M), followed by NSC-658343 (IC 50 , 4.13 M) and NSC-657589 (IC 50 , 7.5 M). On intraperitoneal administration at 5 mg/kg of body weight for 7 days to adult jirds into which B. malayi had been transplanted intraperitoneally, all the compounds killed a significant proportion of the implanted worms. A very similar result was observed in infected mastomys when inhibitors were administered. Docking studies of enzyme and inhibitors and an in vitro tryptophan quenching experiment were also performed to understand the binding mode and affinity. The specific inhibitors of the enzyme showed a higher affinity for the catalytic site of the enzyme than the nonspecific inhibitors and were found to be potent enough to kill the worm (both adults and microfilariae) in vitro as well as in vivo in a matter of days at micromolar concentrations. The findings suggest that these compounds be evaluated against other pathogens possessing a methyltransferase with a DPPY motif and warrant the design and synthesis of more such inhibitors.

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Immunoreactive molecules of Brugia malayi and their diagnostic potential

Cited by 32 publications

References 11 publications

4-Methyl-7-(tetradecanoyl)-2H-1-benzopyran-2-one: a novel DNA topoisomerase II inhibitor with adulticidal and embryostatic activity against sub-periodic Brugia malayi

4-Methyl-7-(tetradecanoyl)-2H-1-benzopyran-2-one: a novel DNA topoisomerase II inhibitor with adulticidal and embryostatic activity against sub-periodic Brugia malayi

Identification of Brugia malayi adult worm molecules immunoreactive with sera of infected animals treated with antifilarial and re-infected with homologous infection and their role in the establishment of infection in Mastomys coucha

Molecular Characterization of an rsmD -Like rRNA Methyltransferase from the Wolbachia Endosymbiont of Brugia malayi and Antifilarial Activity of Specific Inhibitors of the Enzyme

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