ライフサイエンスコーパス: L. donovani

1 L. donovani catabolized glucose to CO(2), succinate, ace

2 L. donovani infection drastically reduced Lys 63-linked

3 L. donovani isolates separated into five groups that lar

4 L. donovani isolates were obtained from splenic aspirati

5 L. donovani mutants deficient in de novo pyrimidine bios

6 L. donovani-challenged IL-12p35 gene knockout (KO) mice

7 L. donovani-infected hamsters underwent xenodiagnoses wi

8 L. donovani-infected IL-13(-/-) mice also responded poor

9 compounds, 16, 17, and 22, were tested in a L. donovani/hamster model.

10 Additionally, L. donovani activates IDO/kynurenine/AHR signaling in BM

11 d polyamine auxotrophy in the Delta adometdc L. donovani.

12 c inflammation and granuloma formation after L. donovani infection.

13 failure of lymph node barrier function after L. donovani infection, which may be related to excessive

14 , and developed severe liver pathology after L. donovani infection that eventually resolved.

15 s, and in the spleen and liver tissues after L. donovani infection, concomitant with an increased exp

16 The action of IL-12 against L. donovani was TNF-alpha dependent and required the act

17 Five congeners were more active against L. donovani than pentamidine.

18 ss superior antileishmanial activity against L. donovani promastigotes whereas CYP51-selective inhibi

19 ht bisbenzofurans displayed activity against L. donovani superior to that of pentamidine.

20 on, it is not essential for immunity against L. donovani, unlike L. major.

21 which are associated with protection against L. donovani.

22 heir contribution to host resistance against L. donovani is not clear.

23 e of IL-17A rendering susceptibility against L. donovani by regulating the IFN-gamma response and pro

24 ere highly active with IC(50) values against L. donovani amastigotes of 0.5 +/- 0.2 and 2.3 +/- 0.8 m

25 ous tumor necrosis factor-alpha (TNF-alpha): L. donovani infection induced TNF-alpha mRNA expression

26 Our results suggest that, although L. donovani evades host immune response, at least in par

27 Previous efforts to generate an L. donovani strain deficient in both hypoxanthine-guanin

28 ntention of identifying cDNA sequences in an L. donovani amastigote cDNA library that collectively or

29 the Ufm1-mediated modifications, we made an L. donovani Ufm1 null mutant (Ufm1(-/-)).

30 played high activity against T. cruzi 14 and L. donovani 17, 19, 29.

31 nd 2.6 microM against cultured T. brucei and L. donovani amastigote-like forms, surpassing the activi

32 Leishmania (Leishmania mexicana complex and L. donovani) has been established.

33 inhibit sterol biosynthesis in T. cruzi and L. donovani by the inhibition of the enzyme sterol 24-me

34 ainst the intact parasites P. falciparum and L. donovani.

35 gainst T. b. rhodesiense, P. falciparum, and L. donovani combined with high antitrypanosomal efficacy

36 st T. brucei rhodesiense, P. falciparum, and L. donovani compared to pentamidine.

37 gainst T. b. rhodesiense, P. falciparum, and L. donovani.

38 Vector-transmitted L. infantum and L. donovani caused >/=5-fold increase in spleen weight c

39 y have implications for human S. mansoni and L. donovani co-infections and also demonstrate that gran

40 g activity against T. brucei rhodesiense and L. donovani.

41 confirming that Wnt5a signaling antagonizes L. donovani infection.

42 despite the development of a functional anti-L. donovani Th1 response that can mediate granuloma form

43 demonstrate the potential of live-attenuated L. donovani parasites as pan-Leishmania species vaccines

44 xicana infection, suggesting that attenuated L. donovani can provide protection against heterologous

45 Genetic analysis has authenticated L. donovani uracil phosphoribosyltransferase (LdUPRT), a

46 CYP5122A1 is essential for both L. donovani promastigotes in culture and intracellular a

47 cessary for the viability and growth of both L. donovani promastigotes and amastigotes and intimate t

48 their sterol from leucine; L. braziliensis, L. donovani and L. tropica apparently produced less ster

49 effective for the treatment of VL caused by L. donovani and mediates its antileishmanial activity by

50 ia and Kenya, where the disease is caused by L. donovani Here, we report the discovery and characteri

51 (70 mg/kg) for the treatment of VL caused by L. donovani.

52 rast, IL-12p40 expression is not elicited by L. donovani, the etiological agent of deadly visceral le

53 on phagocytosis or on cytokines released by L. donovani-infected macrophages, such as interleukin-1b

54 mount importance of AAH to purine salvage by L. donovani.

55 sphatase activity constitutively secreted by L. donovani promastigotes is composed of two (histidine)

56 -2 were shown to be actively transcribed by L. donovani promastigotes by reverse transcription (RT)

57 Cht1 was shown to be actively transcribed by L. donovani promastigotes using reverse transcription an

58 funneled to hypoxanthine and/or xanthine by L. donovani, and that the purine sources within the macr

59 R-TS gene knockouts derived from L. chagasi, L. donovani, or L. major did not protect against L. chag

60 a deleterious role in the outcome of chronic L. donovani infection.

61 rasites of the Leishmania donovani complex - L. donovani and L. infantum - cause the fatal disease vi

62 In contrast, L. donovani and Leishmania major mutants deficient solel

63 lished S. mansoni infections fail to control L. donovani growth in the liver and spleen.

64 iating liver immunopathology and controlling L. donovani growth in TCCR-/- mice.

65 -screening these compounds against T. cruzi, L. donovani, and S. mansoni.

66 In cultured L. donovani and T. brucei, treatment with 5 and 0.5 micr

67 Studies with nucleoside transport-deficient L. donovani indicate that this phenomenon is mediated by

68 ed by a live attenuated centrin gene-deleted L. donovani (LdCen(-/-) ) parasite vaccine.

69 ether a live attenuated centrin gene-deleted L. donovani (LdCen1(-/-)) parasite can persist and be bo

70 lated in Deltahgprt and Deltahgprt/Deltaaprt L. donovani mutants.

71 cently, we have demonstrated that a Deltaodc L. donovani null mutant lacking ornithine decarboxylase

72 The Deltaodc L. donovani exhibited an auxotrophy for polyamines that

73 ia species responsible for visceral disease (L. donovani), as well as species associated with persist

74 trafficking and hepatic inflammation during L. donovani infection, it is not essential for immunity

75 y recruited into the spleen and liver during L. donovani infection and they are preferential targets

76 ruitment of Ly6C(hi) iMOs into organs during L. donovani infection, and adaptive transfer of wild typ

77 6C(hi) iMOs into the liver and spleen during L. donovani infection using a CCR2 antagonist reduces th

78 risingly, a group of five cDNAs that encoded L. donovani histone proteins.

79 omomycin selectively inhibits the eukaryotic L. donovani, but not human, ribosome.

80 t protective manner to animals with existing L. donovani infection.

81 Thus, in experimental L. donovani infection in the liver, TLR4 signaling upreg

82 del using a transgenic luciferase-expressing L. donovani parasite and longitudinally quantified the i

83 Finally, L. donovani induces PPAR-gamma binding on the 11betaHSD1

84 esis is an essential nutritional pathway for L. donovani promastigotes.

85 etoplastida a gene encoding for centrin from L. donovani.

86 etoplastid species, putative stem-loops from L. donovani and Trypanosoma brucei nucleobase transporte

87 ry acid phosphatase (SAcP) was purified from L. donovani culture supernatants and amino-acid sequence

88 nvestigation revealed a key mechanism of how L. donovani exploits TCTP to establish infection within

89 t catalyses beta-oxidation of fatty acids in L. donovani.

90 hway in Leishmania, has not been analyzed in L. donovani To test ARG function in intact parasites, we

91 Consequently, in L. donovani infected BALB/c mice, IL-13 promotes hepatic

92 chemical and biological role of CYP5122A1 in L. donovani and provide an important foundation for deve

93 Expression of ISP2 was not detected in L. donovani, and a transgenic line constitutively expres

94 phosphatases, thioredoxin, SOCS, and Egr1 in L. donovani-infected macrophages was found to be unaffec

95 t version of the Trypanosoma cruzi enzyme in L. donovani resulted in the formation of inactive cross-

96 ated/inactive form of the parasite enzyme in L. donovani significantly reduced their release of secre

97 ADOMETDC establishes that it is essential in L. donovani promastigotes and a potential target for the

98 icate that it is constitutively expressed in L. donovani promastigotes.

99 In fact, in L. donovani promastigotes, we verified for 7 a decrease

100 hydrolase was localized to specific foci in L. donovani promastigotes by immunofluorescent assays.

101 is suggests that it is a single copy gene in L. donovani, and its homologues are present in members r

102 genetically that ODC is an essential gene in L. donovani, define the polyamine requirements of the pa

103 Low or absent expression of parasite ISP2 in L. donovani is necessary to preserve the activation of t

104 ogenous IL-10 primarily regulates killing in L. donovani infection by suppressing production of and r

105 on of the adaptation of energy metabolism in L. donovani and other species suggests that the energy m

106 sites, we generated Deltaarg null mutants in L. donovani and evaluated their ability to proliferate i

107 Similar results were noted in L. donovani-infected wild type mice after transient miR-

108 Significantly, MZMs were preserved in L. donovani-infected B6.TNF-alpha(-/-) mice or mice that

109 ding this large (> 358 kDa) motor protein in L. donovani.

110 cription factor was significantly reduced in L. donovani-infected macrophages and required de novo tr

111 e show that the enhanced early resistance in L. donovani-infected mice is entirely due to the activit

112 mutations in antimony clinical resistance in L. donovani.

113 ucing organ parasite burden significantly in L. donovani-infected BALB/c mice.

114 gg granulomas may thus explain the increased L. donovani burden in the liver and spleen.

115 terized the lipophosphoglycan from an Indian L. donovani isolate.

116 aling, revamping Wnt5a signaling can inhibit L. donovani infection, irrespective of drug sensitivity

117 onally, four compounds were found to inhibit L. donovani cysteine protease.

118 mpounds 14, 15, and 25 selectively inhibited L. donovani at nanomolar concentrations and showed much

119 Interestingly, L. donovani-infected TCCR-/- mice controlled the parasit

120 -gamma in host defense against intracellular L. donovani, the efficacy of IFN-gamma delivered by gene

121 y in BALB/c mice which control intracellular L. donovani via an IL-12- and interferon-gamma (IFN-gamm

122 s required early on to control intracellular L. donovani, support granuloma development, and mediate

123 Sb inhibited but did not kill intracellular L. donovani (2% killing versus 76% in controls).

124 to restrict the replication of intracellular L. donovani.

125 to emerge and control residual intracellular L. donovani infection.

126 L-12 in acquired resistance to intracellular L. donovani and suggest that IL-12 is active in the cell

127 induce a cross-reactive Th2 response to live L. donovani.

128 d multi-copy genes in L. mexicana, L. major, L. donovani, and L. infantum, we demonstrate how this to

129 was significant uptake of L. tropica by MCs, L. donovani was not phagocytosed.

130 The surprising ability of mutant L. donovani lacking HGPRT, APRT, and/or AK to incorporat

131 erum also immunoprecipitated both the native L. donovani 50-kDa Cht1 protein and the native chitinase

132 Furthermore, antisera to native L. donovani SAcP immunoprecipitated in vitro transcripti

133 Our data revealed that L. major, but not L. donovani, induces expression of IRF2, IRF7, and IFIT5

134 entification of the gene encoding this novel L. donovani enzyme.

135 nd characterization of two new biomarkers of L. donovani (Ld-mao1 and Ld-ppi1) present in the urine o

136 Our results reveal the complexity of L. donovani evolution in the ISC in response to drug tre

137 nd that miR155 contributes to the control of L. donovani but is not essential for infection resolutio

138 sitic mechanisms were involved in control of L. donovani infection in miR155KO mice.

139 ishmaniasis (VL) by monitoring the course of L. donovani infection in TCCR-deficient C57BL/6 (TCCR-/-

140 n the lymph node barrier to dissemination of L. donovani is related to insufficient numbers of lymph

141 ion and increased the early dissemination of L. donovani.

142 s to track the evolution and epidemiology of L. donovani from the ISC.

143 Expression of L. donovani hgprt constructs in Escherichia coli indicat

144 ling of L. tropica and to a lesser extent of L. donovani.

145 l for the growth of the promastigote form of L. donovani in culture, that all uracil and pyrimidine n

146 wth of the intracellular amastigote forms of L. donovani and T. cruzi, respectively, at a concentrati

147 The open reading frame of L. donovani NMT has been amplified and used to overprodu

148 lso highlights the non-canonical function of L. donovani tyrosyl-tRNA synthetase.

149 plasma significantly enhanced the growth of L. donovani amastigotes in human macrophages.

150 We report poor intracellular growth of L. donovani in macrophages from knockout mice for NE (el

151 In summary, more than half of L. donovani associated CL wounds harboured biofilms and

152 ting IL-13 or TGF-beta enabled inhibition of L. donovani replication but little parasite killing; ant

153 isms by which resistant clinical isolates of L. donovani induce intracellular events relevant to drug

154 and 3) lower miltefosine-induced killing of L. donovani.

155 Heterozygous knockouts of L. donovani HSP78 (LdHSP78+/-) and Leishmania mexicana H

156 oni egg granuloma, consistent with a lack of L. donovani granuloma assembly in this tissue microenvir

157 ecies suggests that the energy metabolism of L. donovani is inefficient but is well suited to the env

158 Moreover, live microscopy of L. donovani-infected macrophages treated with Wnt5a demo

159 racterized a drug-resistant clonal mutant of L. donovani (TUBA5) that is deficient in LdNT1 transport

160 tional lethal Deltahgprt/Deltaxprt mutant of L. donovani that establishes that L. donovani salvages p

161 ic cells in the skin-draining lymph nodes of L. donovani-infected malnourished mice.

162 components of the purine salvage pathway of L. donovani, both ASL and ADSS are cytosolic enzymes.

163 ovel role for ceramide in the perspective of L. donovani infection and help formulate an antileishman

164 Although resolution of L. donovani infection requires iNOS, residual visceral i

165 Selenoproteins of L. donovani are not required for the growth of the proma

166 ococci are rapidly trapped in the spleens of L. donovani-infected mice.

167 ival and growth of the promastigote stage of L. donovani and intimate an important, if not crucial, r

168 purine salvage by both life cycle stages of L. donovani and authenticate ASL as a potential drug tar

169 T cell responses during the early stages of L. donovani infection.

170 AH is expressed in both life cycle stages of L. donovani, whereas subcellular fractionation and immun

171 , were tested against the Khartoum strain of L. donovani in a hamster model using chloralin (2) and G

172 gene replacement within a virulent strain of L. donovani.

173 ted sand flies favor the transmissibility of L. donovani by infected hosts, owing to a systemic effec

174 The transmission of L. donovani from sick hamsters to flies was surprisingly

175 On L. donovani infection, miR-21KO mice exhibited significa

176 vidence indicating (i) enhanced control over L. donovani after transfer of normal C57BL/6 spleen cell

177 In the first phase, L. donovani promastigotes induce activation of acid sphi

178 ivity against a range of clinically relevant L. donovani and L. infantum isolates.

179 with antimony drug-sensitive and -resistant L. donovani, we noted disruption in the steady-state lev

180 in the drug sensitive and antimony-resistant L. donovani clinical isolates.

181 The emergence of antimony-resistant L. donovani strains appears to be a cause of treatment f

182 ing genes in laboratory-maintained resistant L. donovani lines.

183 J774 and THP-1-derived macrophages restrains L. donovani-induced cortisol levels by inhibiting 11beta

184 s compared with ones with antimony-sensitive L. donovani (Sb(S)LD) infection.

185 The CL3 and CL179 qPCR could detect a single L. donovani-infected macrophage.

186 transfer of DCs pulsed ex vivo with soluble L. donovani Ags (SLDA) to naive mice induced the Ag-spec

187 uce protection against cutaneous or systemic L. donovani challenge.

188 to meet the polyamine requirement, and that L. donovani does not express the enzymatic machinery for

189 yte and macrophage immune functions and that L. donovani infection can suppress the gene as an immune

190 ies using in vitro approaches confirmed that L. donovani infection in macrophages suppresses AIF1 exp

191 Collectively, our findings demonstrate that L. donovani exploits specific histone lysine methyltrans

192 We further demonstrate that L. donovani infection leads to expansion of HSCs in a p1

193 In this work we demonstrate that L. donovani UMPS (LdUMPS) is an essential enzyme in prom

194 We discovered that L. donovani alpha-SNAP (Ldalpha-SNAP) genes are transcri

195 mutant of L. donovani that establishes that L. donovani salvages purines primarily through hypoxanth

196 Collectively, our results imply that L. donovani orchestrates different SOCS isoforms to impa

197 In this study, we observed that L. donovani induced the expression of histone lysine met

198 (BMM s) and CD4(+) T cells, we observed that L. donovani preferentially upregulates SOCS1 and SOCS3 e

199 We propose that L. donovani utilizes the host NE-TLR machinery to induce

200 n immunoprecipitation analysis revealed that L. donovani facilitated H3K36 dimethylation at TNF-alpha

201 In vitro studies clearly show that L. donovani-infected HSCs induce CD4(+) T cells to becom

202 Collectively our results showed that L. donovani exploited the macrophage anti-apoptotic prot

203 Taken together, these results suggest that L. donovani may exploit SOCS for subverting macrophage a

204 These results suggest that L. donovani might exploit host A20 to inhibit the TLR2-m

205 Within the catalytic domain, the L. donovani SAcPs possess two conserved consensus sequen

206 ed a single copy ORF capable of encoding the L. donovani chitinase (Ld Cht1, 1374 bp).

207 eading frames (ORFs) capable of encoding the L. donovani SAcP (SAcP-1, 2052 bp and SAcP-2, 2124 bp).

208 r and biochemical level, a cDNA encoding the L. donovani XPRT was isolated by functional complementat

209 Together, the results for the L. donovani-infected livers of chemokine-deficient mice

210 nvestigate the impact of phosphosites in the L. donovani heat shock protein 90.

211 tivity catalyzed by the beta5 subunit of the L. donovani proteasome.

212 lesion in Escherichia coli implied that the L. donovani ASL could also recognize 5-aminoimidazole-(N

213 These data demonstrate that the L. donovani HGPRT is compartmentalized exclusively withi

214 croscopy were employed to establish that the L. donovani HGPRT is localized exclusively to the glycos

215 proximately 33% amino acid identity with the L. donovani hypoxanthine-guanine phosphoribosyltransfera

216 and substrate specificity data identify this L. donovani nucleoside hydrolase as a nonspecific nucleo

217 anced resistance of p110delta(D910A) mice to L. donovani infection is due in part to impaired expansi

218 cert to prevent acquisition of resistance to L. donovani, (b) reemphasize the capacity of IL-12 to re

219 but STAT1(-/-) mice were highly resistant to L. donovani and developed less immunopathology, whereas

220 acterize chemokine action in the response to L. donovani and also reemphasize that (i) recruited mono

221 t is involved in mediating susceptibility to L. donovani.

222 y monocytes, which mediate susceptibility to L. donovani.

223 Unlike wild type L. donovani, Deltaadss and Deltaasl parasites in culture

224 Unlike wild type L. donovani, the Deltahgprt/Deltaxprt knock-out cannot g

225 ine nucleobases and nucleosides as wild type L. donovani.

226 ibitor of ODC, inhibited growth of wild-type L. donovani amastigotes and effectively cured macrophage

227 results showed that compared with wild-type L. donovani infection, LdCen(-/-) parasites induce signi

228 These studies validate L. donovani NMT as a potential target for development of

229 everal IFN response genes in L. major versus L. donovani DC infections.

230 -targeted gene replacement within a virulent L. donovani background.

231 arget for therapeutic inhibition in visceral L. donovani infection.

232 t the failure of PE mice to resolve visceral L. donovani infection likely represents expression of mu

233 studies, these data support a model in which L. donovani amastigotes readily salvage ornithine and ha

234 e Syrian hamster (Mesocricetus auratus) with L. donovani reproduced the clinicopathological features

235 Following systemic challenge with L. donovani, mice immunized with 6 of these 15 sublibrar

236 so previously observed in mice infected with L. donovani, may thus account for the selective loss of

237 CS) genes in human macrophages infected with L. donovani.

238 (-/-) mice to control primary infection with L. donovani and to respond to chemotherapy.

239 Three days after infection with L. donovani promastigotes, the total extradermal (lymph

240 of these genes in response to infection with L. donovani, the cause of visceral leishmaniasis (VL), w

241 d not increase in response to infection with L. donovani.

242 VL caused by infection of C57BL/6 mice with L. donovani and identified an early suppressive role for

243 ecreted or nonsecreted chimeric protein with L. donovani 3' nucleotidase (NT-OVA).

244 YM1, Arg-1, and MRC-1 genes, compared to WT L. donovani-infected mice.

245 asites (compared to that with wild-type [WT] L. donovani parasites) induced significantly higher prod