ライフサイエンスコーパス: M. leprae

1 M. leprae infection success was also dependent of the gl

2 M. leprae invasion of Schwann cells leads to the neurolo

3 M. leprae OxyR was overproduced and purified, and its bi

4 M. leprae recovered from recipient mice fed control diet

5 M. leprae recovered from target Mphi incubated with norm

6 M. leprae recovered from target Mphi possessed high meta

7 M. leprae retained 56% viability in Schwann cells for 3

8 M. leprae sigE was found to be capable of complementing

9 M. leprae was detected in crude cell lysates of skin bio

10 M. leprae-mediated OASL expression was dependent on cyto

11 M. leprae-sonicate-induced IFN-gamma was similar for all

12 The HD-DDS-ML assay detected as few as 100 M. leprae organisms present in homogenates of human skin

13 Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins s

14 erent VNTR loci and examined a battery of 12 M. leprae strains derived from patients in different reg

15 ercome and has allowed the genotyping of 475 M. leprae strains from six different countries.

16 nase inhibitor PKI-166 effectively abrogates M. leprae-induced myelin damage in in vitro and in vivo

17 In addition, M. leprae-infected granuloma macrophages (Mphi) from EFA

18 ma to trigger antimicrobial activity against M. leprae in infected monocytes.

19 R2/1-mediated antimicrobial activity against M. leprae.

20 Antibodies directed against M. leprae PGL-I represent a useful biomarker for detecti

21 antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30.

22 BCG30 induced significant protection against M. leprae challenge.

23 d significantly augmented protection against M. leprae challenge.

24 3/GLA-SE may confer cross-protection against M. leprae infection.

25 berculosis, induces cross-protection against M. leprae that is comparable or potentially superior to

26 response during leprosy we have developed an M. leprae ear infection model.

27 assay relies on the PCR amplification of an M. leprae-specific 231-bp fragment of folP1 containing c

28 The ability of IFN-beta and M. leprae to induce IL-10 was diminished by IL-27 knockd

29 sis complex, the BCG strain of M. bovis, and M. leprae.

30 r 1 month of incubation at 33 degrees C, and M. leprae retained 53% viability.

31 rabinomannan from M. tuberculosis Erdman and M. leprae mycolylarabinogalactan peptidoglycan were the

32 sults thus indicate that M. lepromatosis and M. leprae diverged approximately 10 million years ago.

33 ibed above indicate that M. lepromatosis and M. leprae diverged from a common ancestor after the mass

34 ncestor (MRCA), and both M. lepromatosis and M. leprae have since accumulated new pseudogenes or acqu

35 nt of these genes placed M. lepromatosis and M. leprae in a tight cluster with long terminal branches

36 els from England, Ireland, and Scotland, and M. leprae in squirrels from Brownsea Island, England.

37 M. tuberculosis, M. avium, M. smegmatis, and M. leprae.

38 rative genomic analysis of these strains and M. leprae strains from Asia and Brazil identified 51 sin

39 ht-binding inhibitors of M. tuberculosis and M. leprae InhA.

40 ed nanomolar Kis against M. tuberculosis and M. leprae InhA.

41 ilar pumps in Mycobacterium tuberculosis and M. leprae may play a comparable role.

42 ps gene clusters in both M. tuberculosis and M. leprae, it should be possible to test the postulated

43 heat shock chaperone, of M. tuberculosis and M. leprae, while that of Ndk shows significant identity

44 rtant pathogens, such as M. tuberculosis and M. leprae.

45 Anti-M. leprae ESAT-6 polyclonal and monoclonal antibodies an

46 rIL-18 augmented M. leprae-induced IFN-gamma in tuberculoid patients, but

47 In contrast with Mtb and BCG, M. leprae did not induce DC activation/maturation as mea

48 al nerve may involve adhesion events between M. leprae (or M. leprae-parasitized macrophages) and the

49 have examined the early interactions between M. leprae and monocytes from healthy human donors.

50 d in areas where exposure to armadillo-borne M. leprae was possible.

51 Transcription of plasmid-borne M. leprae oxyR and ahpC was investigated in M. smegmatis

52 ed levels of Mphi-generated PGE2, induced by M. leprae or its constituents, could act as an endogenou

53 e determined cytokines/chemokines induced by M. leprae proteins in blood of leprosy patients and ende

54 axonal damage are not directly initiated by M. leprae but by infected macrophages that patrol axons;

55 kin-10 (IL-10), were induced in monocytes by M. leprae in vitro and preferentially expressed in disse

56 CD40 ligation, nor was CD40L up-regulated by M. leprae.

57 ta suggest that T cell activation in situ by M. leprae in tuberculoid leprosy leads to local up-regul

58 ed by real-time PCR after the stimulation by M. leprae antigens in the PBMC (peripheral blood mononuc

59 of the granulomatous response during chronic M. leprae infection.

60 differential PCR revealed that 221 contained M. leprae whereas only six, all from Mexico, harbored M.

61 ith SNP type 3I-1, ancestral to contemporary M. leprae isolates found in southern states of America a

62 In contrast, M. leprae from recipient mice fed the EFA-deficient (EFA

63 In contrast, M. leprae-induced IL-12 production by PBMC from lepromat

64 e possess compensatory mechanisms to control M. leprae growth and feature elements resembling mid-bor

65 gh in itself a weak stimulator of cytokines, M. leprae primed the cells for increased production of t

66 Based on these mutations, a heteroduplex DDS M. leprae (HD-DDS-ML) assay was developed for the simult

67 ermine their suitability for differentiating M. leprae, we developed PCR systems to amplify 5 differe

68 claimed that their macrophages cannot digest M. leprae in vitro; such a defect could explain both lep

69 isms can be used effectively to discriminate M. leprae strains.

70 During M. leprae-induced demyelination, Schwann cells prolifera

71 over a promycobacterial role for OASL during M. leprae infection that directs the host immune respons

72 understanding of the immune response during M. leprae infection and the identification or testing of

73 ouse T-cell hybridomas raised against either M. leprae or M. tuberculosis CFP-10 displayed a cross-re

74 distinct patterns of recognition for either M. leprae or M. tuberculosis CFP-10 peptides.

75 may greatly increase the risk of endoneurial M. leprae bacteremia, and also enhance the risk of ische

76 IL-18 enhanced M. leprae-induced IFN-gamma production rapidly (24 h) by

77 amino acid mismatches between the equivalent M. leprae and M. tuberculosis sequences; of these, eight

78 -gamma was similar for all groups, excluding M. leprae/IFN-gamma as a diagnostic readout.

79 e to provide protection against experimental M. leprae infection.

80 t limit local inflammation upon experimental M. leprae infection.

81 This study explored M. leprae infection in mice deficient in inducible nitri

82 revealed differences at one or more loci for M. leprae present in nerves.

83 thereby securing the intracellular niche for M. leprae.

84 inactivation event described previously for M. leprae.

85 Armadillos are a large natural reservoir for M. leprae, and leprosy may be a zoonosis in the region.

86 The assay was specific for M. leprae in a comparison with results obtained from 14

87 unit serves as an initial neural target for M. leprae.

88 0.862 muM) that was 20-fold greater than for M. leprae ManLAM (KD = 18.69 muM).

89 S values were 14 to 28% of the dS values for M. leprae and Mycobacterium tuberculosis, a more diverge

90 genates from eight leprosy patients and from M. leprae-infected mouse or armadillo tissues infected w

91 In vitro, donor cells from M. leprae-primed mice secreted elevated levels of gamma

92 use the reductase portion of the enzyme from M. leprae shows significant primary structure similarity

93 ide further fine structural data on LAM from M. leprae (LepLAM) and a tuberculosis clinical isolate,

94 cterium leprae infection, which results from M. leprae invasion of the Schwann cell of the peripheral

95 these regions and homologous sequences from M. leprae FAP inhibit fibronectin binding by both M. avi

96 Furthermore, M. leprae hsp treatment significantly suppressed OVA-spe

97 v (RvLAM), LepLAM derived from in vivo grown M. leprae is apparently simpler in its arabinan architec

98 However, M. leprae surface molecules that mediate bacterial invas

99 MLVA identified M. leprae genotype associations for patients with known

100 This study identifies M. leprae-unique Ags, particularly ML2478, as biomarker

101 Conversely, knockdown of hsa-mir-21 in M. leprae-infected monocytes enhanced expression of CAMP

102 ced Stat4 phosphorylation and DNA binding in M. leprae-activated T cells from tuberculoid but not fro

103 e concluded that the massive genome decay in M. leprae does not markedly affect the peptidoglycan bio

104 The protein is expressed in M. leprae and appears in the cell wall fraction.

105 nflammatory infiltration with an increase in M. leprae growth throughout infection.

106 MLVA in M. leprae was highly discriminatory in this population y

107 genes analyzed that were also pseudogenes in M. leprae showed nearly neutral evolution, and their rel

108 n with 10 variable-number tandem repeats, in M. leprae strains obtained from 33 wild armadillos from

109 nking these mutations with DDS resistance in M. leprae has been obtained.

110 pect of the defective heat shock response in M. leprae is the absence of a functional sigH.

111 identical, or almost identical, sequences in M. leprae and M. tuberculosis and would not be suitable

112 tion and was also shown to be upregulated in M. leprae-infected human macrophage cell lineages, prima

113 in other pathogenic mycobacteria, including M. leprae and M. bovis, suggesting that a core of basic

114 Anti-IL-12 partially inhibited M. leprae-induced release of IFN-gamma in the presence o

115 The crystal structures of the inhibited M. leprae and M. tuberculosis InhA complexes provide the

116 humanized ErbB2-specific antibody, inhibits M. leprae binding to and activation of ErbB2 and Erk1/2

117 ence and immunoelectron microscopy on intact M. leprae with mAbs against recombinant (r) ML-LBP21 rev

118 Interestingly, M. leprae-exposed MLR cells secreted increased Th2 cytok

119 yelinated Schwann cells harbor intracellular M. leprae in large numbers.

120 of leprosy, we identified that intracellular M. leprae activated Erk1/2 directly by lymphoid cell kin

121 acrophages infected with live and irradiated M. leprae, as a function of multiplicity of infection un

122 en macrophages were infected with irradiated M. leprae.

123 erodimers mediated cell activation by killed M. leprae, indicating the presence of triacylated lipopr

124 iffer in their ability to digest heat-killed M. leprae in vitro, or in their ability to sustain the v

125 ligate intracellular bacterial pathogen like M. leprae subverts nervous system signaling to propagate

126 acillary leprosy patients, a group who limit M. leprae growth and dissemination.

127 cells, murine macrophages infected with live M. leprae demonstrated little, if any, apoptosis, even w

128 ecause of the lack of a model that maintains M. leprae viability and mimics disease conditions.

129 t a subset of the presumptively mannosylated M. leprae glycoproteins act as ligands for langerin and

130 This brings the 2.8-Mb M. leprae genome sequence to approximately 66% completio

131 ularly ML2478, as biomarker tools to measure M. leprae exposure using IFN-gamma or IFN-inducible prot

132 mpetitively inhibited the laminin-2-mediated M. leprae binding to primary Schwann cells.

133 rLN-alpha2G mediated M. leprae binding to cell lines and to sciatic nerves of

134 rin antibody attenuated rLN-alpha2G-mediated M. leprae adherence, suggesting that M. leprae interacts

135 Similarly, human TLR2 mediated M. leprae-dependent activation of NF-kappaB in transfect

136 We found that, in naive monocytes, M. leprae induced high levels of the negative regulatory

137 Our results suggest that most M. leprae strains from a given country cluster together

138 s viruses and for the virulent mycobacterium M. leprae, may be a novel mechanism that this pathogen u

139 ze peptide Ags from M. tuberculosis, but not M. leprae.

140 The ability of M. leprae ligands to induce the apoptosis of Schwann cel

141 results suggest that the reduced ability of M. leprae to survive at elevated temperatures results fr

142 Therefore, the ability of M. leprae to upregulate hsa-mir-21 targets multiple gene

143 tis; the major site of early accumulation of M. leprae is epineurial.

144 The addition of M. leprae DNA enhanced nonpathogenic Mycobacterium bovis

145 Administration of M. leprae hsp prevented both development of AHR as well

146 uctures of the AG were also found; the AG of M. leprae is smaller than that of M. tuberculosis, altho

147 ector Mphi was necessary for augmentation of M. leprae metabolism by normal effector Mphi as well as

148 d a long-term line, have a higher binding of M. leprae compared to CD209-negative Schwann cells.

149 e is attributable to the specific binding of M. leprae to the laminin-alpha2 (LN-alpha2) chain on Sch

150 n configuration of the peptide side chain of M. leprae did not affect recognition by NOD2 or cytokine

151 The un-cross-linked peptide side chains of M. leprae consist of tetra- and tripeptides, some of whi

152 , MLVA was applied to a global collection of M. leprae isolates derived from leprosy patients and pro

153 ponses accompanied by an apparent deficit of M. leprae-specific antibodies to strong humoral response

154 IFN-gamma could indicate distinct degrees of M. leprae exposure, and thereby the risk of infection an

155 a new tool for the simultaneous detection of M. leprae and of its susceptibility to DDS from a single

156 developed for the simultaneous detection of M. leprae and of its susceptibility to DDS.

157 d diagnostic test for the early detection of M. leprae infection and epidemiological surveys of the i

158 zation and challenge abolished the effect of M. leprae hsp treatment on AHR.

159 ibes a new model for studying the effects of M. leprae on Schwann cells.

160 urface adhesin that facilitates the entry of M. leprae into Schwann cells.

161 have begun to elucidate the early events of M. leprae infection of Schwann cells on a molecular leve

162 h larvae to visualize the earliest events of M. leprae-induced nerve damage.

163 ranuloma Mphi harvested from the footpads of M. leprae-infected athymic nu/nu mice, were cocultured w

164 d the glycosylation of a recombinant form of M. leprae SodC (rSodC) produced in Mycobacterium smegmat

165 Growth of M. leprae was contained for 6 months, but augmented late

166 sults demonstrate that the RuvA homologue of M. leprae is a functional branch-migration subunit.Where

167 cimens we corroborated the identification of M. leprae with detection of mycolic acids specific to th

168 l effector Mphi as well as for inhibition of M. leprae by ACT effector Mphi.

169 Intradermal inoculation of M. leprae into the ear supported not only infection but

170 ngerin and may facilitate the interaction of M. leprae with Langerhans cells.

171 Since the genome sequence of an isolate of M. leprae has become available, multiple-locus variable-

172 s greater discrimination between isolates of M. leprae and enhances the potential of this technique t

173 Two genetic loci in several isolates of M. leprae have previously been demonstrated to contain v

174 21, and 27 bp from four clinical isolates of M. leprae propagated in armadillo hosts were screened by

175 (UDP-N-acetyl-muramate:L-alanine ligase) of M. leprae showed K(m) and V(max) for L-alanine and glyci

176 , specific mechanisms in the localization of M. leprae to peripheral nerve may involve adhesion event

177 We found that the majority of M. leprae-reactive CD1-restricted T cell clones (92%) we

178 cobacterial species, whereas the majority of M. leprae-reactive MHC-restricted T cells were species s

179 Microsatellite mapping of M. leprae represents a useful tool for tracking short tr

180 he patterns of transmission and migration of M. leprae.

181 digan et al. (2017) use a zebrafish model of M. leprae infection to show that infected macrophages pa

182 (i.e., defective macrophage "processing" of M. leprae).

183 Cognate recognition of M. leprae Ag by a T cell clone derived from a tuberculoi

184 inding to the oxyR-ahpC intergenic region of M. leprae was demonstrated.

185 Whole-genome resequencing of M. leprae from one wild armadillo and three U.S. patient

186 d M. smegmatis, the muramic acid residues of M. leprae peptidoglycan are exclusively N acetylated.

187 A genome-wide scan of M. leprae detected 31 putative lipoproteins.

188 Immunohistochemical staining of sections of M. leprae-infected nude mouse footpads resulted in stron

189 Since the sigH of M. leprae is a pseudogene, these data support the conclu

190 States are infected with the same strain of M. leprae.

191 ent study, we have analyzed the structure of M. leprae peptidoglycan in detail by combined liquid chr

192 e exceedingly passive obligate life style of M. leprae with a degraded genome and host cell dependenc

193 nsion of multiple distinct subpopulations of M. leprae.

194 d based on humoral reactivity to a subset of M. leprae protein antigens produced in recombinant form.

195 ling is identified as a downstream target of M. leprae-induced ErbB2 activation that mediates demyeli

196 ptor alpha-dystroglycan as neural targets of M. leprae has not only opened up a new area of scientifi

197 their relative ages were similar to those of M. leprae pseudogenes, suggesting that they were pseudog

198 ol diets, were given an adoptive transfer of M. leprae-primed, T-cell-enriched lymphocytes.

199 d to allow monitoring of the transmission of M. leprae in different countries where leprosy is endemi

200 sue macrophages and to mediate the uptake of M. leprae, was present on Schwann cells, colocalizing wi

201 in their ability to sustain the viability of M. leprae in tissue culture; that monocytes, macrophages

202 anuloma may markedly affect the viability of M. leprae residing in Mphi in the lepromatous lesion.

203 n was associated with decreased viability of M. leprae that was concomitant with upregulation of eith

204 f mycolic acids specific to the cell wall of M. leprae and persistent in the skeletal samples.

205 lly, it was determined that the cell wall of M. leprae contained significantly more mycolic acids att

206 ffinity to glycoproteins in the cell wall of M. leprae.

207 nvolve adhesion events between M. leprae (or M. leprae-parasitized macrophages) and the endothelial c

208 ion of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M.

209 Overall, M. leprae were found in endothelial cells in 40% of epin

210 quisition and uptake mechanism in pathogenic M. leprae, as the siderophores from this organism are ve

211 n efficiently transport iron into pathogenic M. leprae, which is responsible for leprosy, in addition

212 bined effect of IL-12 and IL-18 in promoting M. leprae-specific type 1 responses.

213 aised in mice or rabbits against recombinant M. leprae and M. tuberculosis CFP-10 proteins reacted on

214 f these patients also had rifampin-resistant M. leprae.

215 withstanding these discriminatory responses, M. leprae proteins did not distinguish patients from EC

216 Importantly, and in contrast to subcutaneous M. leprae footpad infection, systemic M. leprae-specific

217 aneous M. leprae footpad infection, systemic M. leprae-specific gamma interferon and antibody respons

218 indicate that M. lepromatosis is closer than M. leprae to the MRCA, and a Bayesian dating analysis su

219 d from 14 species of mycobacteria other than M. leprae and four bacterial species known to colonize h

220 stinctive properties among the hsp, and that M. leprae hsp may have a potential therapeutic role in t

221 We concluded that M. leprae could modulate host cell glucose metabolism to

222 In this study, we demonstrate that M. leprae-specific mouse T-cell lines recognize several

223 We determined that M. leprae lacks a protective heat shock response as a re

224 Here we provide evidence that M. leprae-induced demyelination is a result of direct ba

225 Previous reports have indicated that M. leprae is a poor activator of macrophages and dendrit

226 additional cytokines/chemokines showed that M. leprae and ML2478 induced significantly higher concen

227 Our data suggest that M. leprae does not induce and probably suppresses in vit

228 Taken together, our results suggest that M. leprae plays an active role to control the release of

229 These data suggest that M. leprae upregulates IL-1Ra by a TOLLIP-dependent mecha

230 ning in extracellular areas, suggesting that M. leprae CFP-10, like its homologue in M. tuberculosis,

231 ediated M. leprae adherence, suggesting that M. leprae interacts with cells by binding to beta4 integ

232 The M. leprae genotype of patients with foreign exposure gen

233 The M. leprae-specific recall response of CD4+ T cell clones

234 ant fragments of LN-alpha2 (rLN-alpha2), the M. leprae-binding site was localized to the G domain.

235 ine efficacy was assessed by enumerating the M. leprae bacteria per footpad.

236 osis were shown to be either absent from the M. leprae genome or were present as pseudogenes.

237 ides were synthesized based on data from the M. leprae genome, each peptide containing three or more

238 ns as a probe, a major 28-kDa protein in the M. leprae cell wall fraction that binds alpha2 laminins

239 PGL-1 is involved in the M. leprae invasion of Schwann cells through the basal la

240 superoxide dismutase C (SodC) protein of the M. leprae cell wall was identified as a langerin-reactiv

241 Unusual features of the M. leprae genome include large polyketide synthase (pks)

242 iously selected by in silico analyses of the M. leprae genome.

243 ion resulting from direct interaction of the M. leprae-specific phenolic glycolipid 1 (PGL-1) with my

244 The identification of the M. leprae-targeted Schwann cell receptor, dystroglycan,

245 nes, which were recently defined through the M. leprae genome project and which encode a putative sul

246 of this important class of transporters, the M. leprae Nramp was expressed in Escherichia coli.

247 ncestor around 27,000 years ago, whereas the M. leprae strain is closest to one that circulated in Me

248 eotide 3'-phosphodiesterase), along with the M. leprae antigen PGL-1 in the peripheral nerve biopsy s

249 ntigen 85B, which is 85% homologous with the M. leprae homolog (r30ML).

250 Deduced amino acid sequence of this M. leprae laminin-binding protein predicts a 21-kDa mole

251 Thus, M. leprae ESAT-6 shows promise as a specific diagnostic

252 Thus, M. leprae may use linkage between the extracellular matr

253 cells and subsequent Schwann cell binding to M. leprae, whereas Th1 cytokines did not induce CD209 ex

254 ers of adaptive immune responses, exposed to M. leprae, Mycobacterium tuberculosis (Mtb), and Mycobac

255 ich could be used to distinguish exposure to M. leprae from exposure to Mycobacterium tuberculosis or

256 and maturation markers following exposure to M. leprae.

257 hose induced during asymptomatic exposure to M. leprae.

258 Host immunity to M. leprae determines the diversity of clinical manifesta

259 rrelated directly with effective immunity to M. leprae, as assessed by the clinical course of infecti

260 licate the response of innate macrophages to M. leprae PGL-1 in initiating nerve damage in leprosy.

261 Myelinated Schwann cells were resistant to M. leprae invasion but undergo demyelination upon bacter

262 TLR2Arg(677)Trp was abolished in response to M. leprae and Mycobacterium tuberculosis.

263 ibited an elevated proliferative response to M. leprae antigen.

264 These data suggest that Th response to M. leprae determines IL-12Rbeta2 expression and function

265 In mice, TNF-alpha production in response to M. leprae was essentially absent in TLR2-deficient macro

266 , T cells did not proliferate in response to M. leprae-stimulated DC.

267 enic mycobacteria including M. tuberculosis, M. leprae, and M. avium but not by nonpathogenic mycobac

268 seases caused by Mycobacterium tuberculosis, M. leprae and M. avium, cause significant morbidity and

269 the treatment of Mycobacterium tuberculosis, M. leprae, and M. avium complex infections.

270 However, a unique M. leprae genotype (3I-2-v1) was found in 28 of the 33 w

271 hwann cells and macrophages bind and take up M. leprae, contributing to the pathogenesis of leprosy.

272 nged 2.5 months later by injection of viable M. leprae into each hind footpad.

273 A model was developed using viable M. leprae, rat Schwann cells, and Schwann cell-neuron co

274 After 2 weeks, M. leprae bacilli were harvested from the recipient mice

275 es required for amino acid synthesis whereas M. leprae has a defective heme pathway.

276 To understand whether M. leprae fails to elicit an optimal Th1 immune response

277 read to growth-permissive macrophages, while M. leprae PGL-1 induces macrophages to cause nerve demye

278 CD3-CD56+ (NK) subset, rIL-15 combined with M. leprae induced the expansion of CD3+CD56+ T cells.

279 nized mice were experimentally infected with M. leprae, both cellular infiltration into the local lym

280 se, finding that infection of monocytes with M. leprae induces IL-32 and DC differentiation in a NOD2

281 imulation of TOLLIP-deficient monocytes with M. leprae produced significantly less IL-1Ra (P < .001),

282 he level of matching of these sequences with M. leprae sequences was 90.9%, which substantiated the s

283 CE (caspase-1), in monocytes stimulated with M. leprae compared with Mycobacterium bovis BCG stimulat

284 Treatment with M. leprae hsp also resulted in suppression of IL-4 and I