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 were obtained from splenic aspirati

4 L. donovani mutants deficient in de novo pyrimidine bios

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

6 L. donovani-infected hamsters underwent xenodiagnoses wi

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

36 confirming that Wnt5a signaling antagonizes L. donovani infection.

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

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

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

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

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

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

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

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

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

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

47 -2 were shown to be actively transcribed by L. donovani promastigotes by reverse transcription (RT)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

65 6C(hi) iMOs into the liver and spleen during L. donovani infection using a CCR2 antagonist reduces th

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

102 to restrict the replication of intracellular L. donovani.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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