Antibiotics which Target the Wolbachia Endosymbionts of Filarial Parasites: A New Strategy for Control of Filariasis and Amelioration of Pathology

Pfarr, Kenneth; Hoerauf, Achim

doi:10.2174/138955706775475984

Cited by 31 publications

(34 citation statements)

References 61 publications

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“…Attempts to infect Caenorhabditis elegans or insect cell lines with nematode Wolbachia that are then able to replicate have been unsuccessful (B. Slatko, unpublished results). This probably reflects the fact that the Wolbachia in nematodes are mutualists, and their hosts have become dependent on their endosymbionts for embryonic and larval development as well as adult survival (Pfarr & Hoerauf, 2006). Furthermore, the significant phylogenetic distance of the hosts should also be considered.…”

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confidence: 99%

On the taxonomic status of the intracellular bacterium Wolbachia pipientis: should this species name include the intracellular bacteria of filarial nematodes?

Pfarr¹,

Foster

Slatko

et al. 2007

International Journal of Systematic and Evolutionary Microbiology

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On the taxonomic status of the intracellular bacterium Wolbachia pipientis: should this species name include the intracellular bacteria of filarial nematodes? The recent article by Lo et al. (2007) aiming to recognize the Wolbachia endobacteria of arthropods and filarial nematodes as Wolbachia pipientis, while admirable for attempting to codify the nomenclature in this field of research, may not address the stark differences of the endobacteria found in nematodes compared with the endobacteria found in arthropods. Lo et al. (2007) propose that all endobacteria of arthropods and nematodes commonly called Wolbachia be formally declared as Wolbachia pipientis. Part of their reasoning is based on the difficulty of assigning the strains to monophyletic species due to the lack of an appropriate outgroup and the fact that to name arthropod strains after the species they infect would be unwieldy because of the huge number of arthropod species infected with these endobacteria (Lo et al., 2007). This was the consensus reached at the 2004 international conference on W. pipientis (Heron Island, Australia, August 2004). However, in 2005, the genome of Wolbachia from the filarial nematode Brugia malayi (wBm) was published (Foster et al., 2005) and compared with the previously published genome of the Wolbachia from Drosophila melanogaster (wMel) (Wu et al., 2004). Analysis of the genome and the biology of the Wolbachia in nematodes argues against including these endobacteria with those from arthropods as W. pipientis.

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confidence: 99%

On the taxonomic status of the intracellular bacterium Wolbachia pipientis: should this species name include the intracellular bacteria of filarial nematodes?

Pfarr¹,

Foster

Slatko

et al. 2007

International Journal of Systematic and Evolutionary Microbiology

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“…As will be explained in the following paragraphs, other than moxidectin and doxycycline, no new antifilarial drugs have been developed, and other drugs which have been studied are either less effective than the current ones, or they are too toxic (table 1) [55][56][57][58]. Moxidectin has been shown to be macrofilaricidal in animal studies not dealing with Onchocerca species [59].…”

Section: Past and Current Control Effortsmentioning

confidence: 99%

Wolbachia Endosymbionts: An Achilles’ Heel of Filarial Nematodes

Hoerauf¹,

Pfarr²

2007

Issues in Infectious Diseases

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Filarial worm infections of humans cause morbidity and even death in developing countries of the tropics. Current antifilarial drug therapies target only the first-stage larvae, requiring many years of annual/biannual treatment. Another problem with controlling filarial infections is the lack of any alternative drugs that can be used in the current mass drug administration programs should resistance develop. Wolbachia, endosymbiotic bacteria that are found in most of the human filarial worms are excellent targets for the discovery of new antifilarial drugs because of their requirement for worm embryogenesis, development and adult survival. Targeting of Wolbachia with antirickettsial drugs has lead to the recommendation of doxycycline for use on an individual basis and may be recommended in areas where resistance to current drugs may develop. More evidence that eliminating the endobacteria reduces adverse reactions to current drug therapies and even reduces early stages of pathology is also accruing. Thus, research is underway to discover new drugs, preferably those already approved for use in humans, that have antiwolbachial activity and work in a shorter time and which can be given to all members of the population. 'Two urns on Jove's high throne have ever stood,The source of evil one, and one of good; From thence the cup of mortal man he fills, Blessings to these, to those distributes ills;To most he mingles both.' HomerFilarial nematode infections are endemic in more than 90 countries of the tropics. In these countries, 200 million individuals are infected and 1.3 billion people are at risk of infection [1][2][3]. The number of people infected is higher than

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“…The activity of tetracycline used against several filarial species has been reported (Hoerauf et al , 2000, indicating the possibility of developing antifilarial agents from antibiotic used alone or in combination with existing filaricides. Since Wolbachia or Wolbachia-derived products have been implicated in the development of pathogenesis in the vertebrate host, their depletion from the filarial parasites may lead to reductions in pathogenesis or adverse side reactions associated with DEC treatment (Taylor 2003;Pfarr and Hoerauf 2006). Adverse reactions after DEC treatment are reported to be due to a burst of inflammatory mediators produced in response to the abrupt excessive release of parasite-associated molecules and the endosymbiotic bacteria Wolbachia (Keiser et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Prior killing of intracellular bacteria Wolbachia reduces inflammatory reactions and improves antifilarial efficacy of diethylcarbamazine in rodent model of Brugia malayi

et al. 2008

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The discovery of the endosymbiont Wolbachia, which has a mutualistic relationship with filarial nematodes, and its importance in filarial parasite biology has provided a lead for developing novel chemotherapeutic agents against human filariasis. Wolbachia also appears to be involved in immunopathological responses as well as adverse reactions after antifilarial therapy. The aim of the present study was to explore the potential of administering anti-Wolbachial therapy before antifilarial treatment to improve the filaricidal efficacy of the present-day filaricide diethylcarbamazine. An additional objective was to minimize host inflammatory reactions using a rodent model Mastomys coucha and Meriones unguiculatus infected with human lymphatic filariid Brugia malayi. We observed: (1) a 40-day treatment schedule of tetracycline alone resulted in delayed reduction in microfilaraemia and a low degree of macrofilaricidal efficacy; (2) tetracycline therapy followed by 100 mg/kg diethylcarbamazine (DEC) x5 days led to marked reduction in microfilaraemia from day 48 onward after initiation of treatment. The combination treatment also brought about approximately 70% death of adult B. malayi and sterilization of 82.3% of the surviving female worms, thus exhibiting remarkable enhancement in the antifilarial activity of DEC; (3) tissue inflammatory reactions and pathogenesis were significantly reduced as observed by histopathology, and peritoneal macrophage mediated oxidative burst shown by fluorescence-activated cell sorting (FACS) analysis using dichlorofluorescein diacetate (DCF-DA); and (4) the characteristic filarial antigen-specific and mitogen-specific cellular unresponsiveness was significantly reversed, possibly due to marked clearance of microfilaraemia. It is therefore advisable to give an anti-Wolbachial antibiotic trial before starting antifilarial therapy to achieve maximum benefits.

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Antibiotics which Target the Wolbachia Endosymbionts of Filarial Parasites: A New Strategy for Control of Filariasis and Amelioration of Pathology

Cited by 31 publications

References 61 publications

On the taxonomic status of the intracellular bacterium Wolbachia pipientis: should this species name include the intracellular bacteria of filarial nematodes?

On the taxonomic status of the intracellular bacterium Wolbachia pipientis: should this species name include the intracellular bacteria of filarial nematodes?

Wolbachia Endosymbionts: An Achilles’ Heel of Filarial Nematodes

Prior killing of intracellular bacteria Wolbachia reduces inflammatory reactions and improves antifilarial efficacy of diethylcarbamazine in rodent model of Brugia malayi

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