Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent

Imamura, Hideo; Downing, Tim; Broeck, Frederik Van den; Sanders, Mandy; Rijal, Suman; Sundar, Shyam; Mannaert, An; Vanaerschot, Manu; Berg, Maya; Muylder, Géraldine De; Dumetz, Franck; Cuypers, Bart; Maes, Ilse; Domagalska, Malgorzata A.; Decuypere, Saskia; Rai, Keshav; Uranw, Surendra; Bhattarai, Narayan; Khanal, Basudha; Prajapati, Vijay Kumar; Sharma, Smriti; Stark, Olivia; Schönian, Gabriele; Koning, Harry P. de; Settimo, Luca; Vanhollebeke, Benoît; Roy, Syamal; Ostyn, Bart; Boelaert, Marleen; Maes, Louis; Berriman, Matthew; Dujardin, Jean‐Claude; Cotton, James A.

doi:10.7554/elife.12613

Cited by 148 publications

(255 citation statements)

References 78 publications

(113 reference statements)

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“…It has been proposed that aneuploidy in Leishmania could be transitory (Rougeron et al, 2015). This is not supported by genomic analyses that deals with natural isolates and not experimental populations (Downing et al, 2011;Imamura et al, 2016). Moreover, even if aneuploidy were transitory, heterozygosity purging at each haploid cycle (Sterkers et al, 2012) should remain.…”

Section: A Debate In the Debate: Unisex/selfing/ Inbreeding Versus 'Smentioning

confidence: 98%

“…An illustrative example of clonet is the L. infantum MLEE MLG MON1, which proves to be genetically heterogeneous by the use of microsatellites . A more recent, striking case is the so-called L. donovani core group in India and Nepal, which is monomorphic with microsatellites, while it exhibits a strong genetic structuration into six congruent monophyletic groups with SNPs (Imamura et al, 2016). The clonet feature does not invalidate population genetics tests based on MLEE and microsatellite polymorphisms.…”

Section: Identical Multilocus Genotypes Are a Relative Notion: Implicmentioning

confidence: 99%

“…It exhibits a clear microclustering (RD pattern), although the most recent common ancestor is estimated to be dated to the year 1959 only (Wong et al, 2015). This shows that 'measurably evolving pathogens' (Biek et al, 2015), that is, pathogens whose epidemiology can be followed up through WGS and time-serial samplings, are not only limited to fastevolving viruses but also concern bacteria (Wong et al, 2015) and even parasitic protozoa (Imamura et al, 2016).…”

Section: Bacteriamentioning

confidence: 99%

“…In the same species, high-resolution typing by WGS/SNP of 204 clinical isolates from Nepal and India (Imamura et al, 2016) reveals a remarkable case of RD pattern. The strains are split into three distinct genetic lines.…”

Section: Parasitic Protozoamentioning

confidence: 99%

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Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

Tibayrenc

Ayala

2017

Advances in Parasitology

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Section: A Debate In the Debate: Unisex/selfing/ Inbreeding Versus 'Smentioning

confidence: 98%

Section: Identical Multilocus Genotypes Are a Relative Notion: Implicmentioning

confidence: 99%

Section: Bacteriamentioning

confidence: 99%

Section: Parasitic Protozoamentioning

confidence: 99%

See 2 more Smart Citations

Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

Tibayrenc

Ayala

2017

Advances in Parasitology

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“…Although the use of amphotericin B and miltefosine has shown limited success in the treatment of kala-azar, with prolonged medication these cases become resistant or unresponsive to treatment. Subsequent transmission of drug resistance by the sandfly contributes to the development of a more severe and endemic disease (7)(8)(9).…”

mentioning

confidence: 99%

Wnt5a Signaling Promotes Host Defense against Leishmania donovani Infection

Chakraborty

Kurati

Mahata

et al. 2017

The Journal of Immunology

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Leishmania donovani infects macrophages, disrupting immune homeostasis. The underlying mechanism that sustains infection remains unresolved. In view of the potential of Wnt5a signaling to support immune homeostasis, we evaluated the interrelationship of Wnt5a signaling and Leishmania donovani infection. Upon infecting macrophages separately with antimony drug–sensitive and –resistant L. donovani, we noted disruption in the steady-state level of Wnt5a. Moreover, inhibition of Wnt5a signaling by small interfering RNA transfection in vitro or by use of inhibitor of Wnt production in vivo led to an increase in cellular parasite load. In contrast, treatment of macrophages with recombinant Wnt5a caused a decrease in the load of antimony-sensitive and -resistant parasites, thus confirming that Wnt5a signaling antagonizes L. donovani infection. Using inhibitors of the Wnt5a signaling intermediates Rac1 and Rho kinase, we demonstrated that Wnt5a-mediated inhibition of parasite infection in macrophages is Rac1/Rho dependent. Furthermore, phalloidin staining and reactive oxygen species estimation of Wnt5a-treated macrophages suggested that a Wnt5a-Rac/Rho–mediated decrease in parasite load is associated with an increase in F- actin assembly and NADPH oxidase activity. Moreover, live microscopy of L. donovani–infected macrophages treated with Wnt5a demonstrated increased endosomal/lysosomal fusions with parasite-containing vacuoles (parasitophorous vacuoles [PV]). An increase in PV–endosomal/lysosomal fusion accompanied by augmented PV degradation in Wnt5a-treated macrophages was also apparent from transmission electron microscopy of infected cells. Our results suggest that, although L. donovani evades host immune response, at least in part through inhibition of Wnt5a signaling, revamping Wnt5a signaling can inhibit L. donovani infection, irrespective of drug sensitivity or resistance.

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Leishmaniases

Chang¹

2021

Encyclopedia of Life Sciences

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Leishmaniases are neglected tropical diseases. The causative agents, Leishmania spp., are transmitted by the blood‐sucking female sand flies. The diseases are largely a zoonosis of canines, rodents and edentates. Humans are accidental dead‐end hosts, except in some places where human–human transmission is indicated by the absence of animal reservoirs. The diseases are present in >100 countries, mainly in tropical and subtropical areas, putting one billion world population at risk with an annual caseload of ∼one million and death in the tens of thousands. Leishmaniases are marked by a spectrum of clinical manifestations, ranging from self‐healing cutaneous lesions to facial mucocutaneous disfiguration to visceralisation with fatal consequence. Clinical managements of visceral leishmaniases rely on several toxic drugs with decreasing efficacy due to the development of drug resistance. Intraphagolysosomal parasitism of macrophages by these parasites is a key feature for considering molecular mechanisms of their virulence relevant to developing effective drugs and vaccines needed. Key Concepts The trypanosomatid protozoa in the genus of Leishmania cause leishmaniases. The diseases are neglected, but very widespread mainly in tropical and subtropical countries. The parasites live briefly in blood‐sucking sand flies and develop into infective promastigotes in the gut lumen. Infected sand flies transmit the parasites among animals, e.g. canines, rodents and edentates. Humans acquire leishmaniases from sand fly bites as a zoonosis with infected wild and domestic animals as the reservoirs. Human leishmaniasis is referred to as anthroponotic where reservoir animals have not been identified. The parasites live in the acidic endosomes/lysosomes of macrophages as amastigotes in the mammalian hosts. There are cutaneous, mucocutaneous and visceral leishmaniases. The spectrum of clinical manifestations results from immunopathology of different host‐parasite interactions. Life‐long immunity to leishmaniases often develops in patients cured of these diseases. Chemotherapy of leishmaniases relies on toxic drugs and loses its effectiveness to drug‐resistance. Visceral leishmaniasis has been brought under control in some endemic countries. Control programs include diagnosis of patients for treatments, surveillance of reservoirs and vectors for elimination. Lack of incentives for drug and vaccine development accounts for the persistence of leishmaniases.

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Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent

Cited by 148 publications

References 78 publications

Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

Wnt5a Signaling Promotes Host Defense against Leishmania donovani Infection

Leishmaniases

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