ライフサイエンスコーパス: M. marinum

1 xclusively at the actin-polymerizing pole of M. marinum.

2 coronin support intracellular replication of M. marinum.

3 d the fruit fly Drosophila melanogaster with M. marinum.

4 o infection of J774 macrophage-like cells by M. marinum.

5 Cultures of a biopsy of the lesion grew M. marinum.

6 s identified immediately upstream of katG in M. marinum.

7 ubstrates in ESX-1 function and secretion in M. marinum.

8 en iron uptake and PDIM and PGL synthesis in M. marinum.

9 .7 and human THP-1 macrophages infected with M. marinum.

10 hat are important for bacterial virulence of M. marinum.

11 logical medium, correlates with virulence in M. marinum.

12 ant colony-forming units in aged cultures of M. marinum.

13 g units from frogs chronically infected with M. marinum.

14 loma where they are productively infected by M. marinum.

15 virulence of Mycobacterium tuberculosis and M. marinum.

16 or the virulence of both M. tuberculosis and M. marinum.

17 s that oxyR is not critical for virulence in M. marinum.

18 54.46 degrees C (53.69 to 55.23 degrees C); M. marinum, 58.91 degrees C (58.28 to 59.55 degrees C);

19 forty-two slowly growing NTM, including 7/7 M. marinum, 7/7 M. kansasii, and 7/11 of other less comm

20 xhibited granulomas and tolerated persistent M. marinum accumulation.

21 teracting protein, and Cdc42 does not affect M. marinum actin tail formation, excluding the participa

22 ate-binding basic motif in N-WASP eliminates M. marinum actin tail formation.

23 e identification and characterization of the M. marinum actin-based motility factor designated mycoba

24 M. marinum AhpC levels detected by immunoblotting, were

25 In the environment, M. marinum also interacts with amoebae, which may serve

26 o bind to the oxyR-ahpC promoter region from M. marinum and additional mycobacterial species.

27 id constructs between MycP(1) and MycP(5) in M. marinum and analyzed their effect on ESX-1 and ESX-5

28 sis, the opportunistic strains M. abscessus, M. marinum and M. avium, and the nonpathogenic strain M.

29 A recent publication in PNAS reported that M. marinum and M. bovis bacillus Calmette-Guerin produce

30 bacteriostatic/bactericidal activity against M. marinum and M. tuberculosis in vitro.

31 y of mariner-based transposon mutagenesis of M. marinum and that M. marinum can be used to study the

32 Interestingly, mel(2) is unique to M. marinum and the M. tuberculosis complex and not prese

33 The largest regulon is observed in M. marinum and the smallest in M. abscessus.

34 ycobacterial models, including M. bovis BCG, M. marinum, and M. smegmatis have significantly contribu

35 trate that the levels of ESX-1 substrates in M. marinum are fine-tuned by negative feedback control,

36 an Xenopus laevis to study host responses to M. marinum at two distinct life stages, tadpole and adul

37 n ESX-5a deletion mutant in the model system M. marinum background was deficient in the secretion of

38 Intracellular M. marinum blocked vacuolar acidification and failed to

39 genetic loci required for ESX-1 secretion in M. marinum but also provide an explanation for the obser

40 o these genes in M. bovis, M. bovis BCG, and M. marinum but not in several other Mycobacterium specie

41 role in the virulence of M. tuberculosis and M. marinum, but the precise molecular and cellular mecha

42 hether LOS composition affects the uptake of M. marinum by professional phagocytes.

43 lar level, M. ulcerans is distinguished from M. marinum by the presence of a virulence plasmid which

44 ransposon mutagenesis of M. marinum and that M. marinum can be used to study the function of M. tuber

45 These findings show that M. marinum can escape into the cytoplasm of infected mac

46 M. marinum causes a chronic granulomatous, nonlethal dis

47 M. marinum causes systemic disease in fish but produces

48 beled substrates indicated that M. bovis and M. marinum cell extracts contain PLC and PLD activities,

49 oscope, we found that the majority of viable M. marinum cells were in nonacidic vacuoles that did not

50 This method has enabled us to isolate 12 M. marinum clones that contain promoter constructs diffe

51 agents against 60 recent clinical strains of M. marinum collected from 10 geographic sites within the

52 However, we were also able to show that M. marinum contains an even larger set of host-specific

53 Therefore, M. marinum contains different sets of virulence factors

54 arinum by heterologous complementation of an M. marinum cosmid library in the nonchromogen Mycobacter

55 atively control esx-1 gene expression in the M. marinum cytoplasm through the conserved WhiB6 transcr

56 e M. marinum wild-type (WT) strain or by the M. marinum DeltaesxBA complemented strain, M. marinum De

57 s, and found that the esxBA-knockout strain (M. marinum DeltaesxBA) upregulated miR-147 to a level th

58 e M. marinum DeltaesxBA complemented strain, M. marinum DeltaesxBA/pesxBA, suggesting that the ESX-1

59 We confirm the previous finding that M. marinum DeltaRD1 mutants are attenuated in adult zebr

60 Here we show that M. marinum DeltasecA2 was attenuated for virulence in bo

61 M. marinum DeltasecA2 was more sensitive to SDS and had

62 Inactivation of oxyR in M. marinum did not affect either virulence in a fish inf

63 e, we describe a laboratory animal model for M. marinum disease in the leopard frog (Rana pipiens), a

64 phage infection, we conducted a screen of an M. marinum DNA library that provides 2.6-fold coverage o

65 Interestingly, M. marinum enters fish monocytes at a 40- to 60-fold-hig

66 nclude that ESX-1 plays an essential role in M. marinum escape from the MCV.

67 oducing pores in MCV membranes, facilitating M. marinum escape from the vacuole and cell-to-cell spre

68 hese results suggest that ESAT-6 secreted by M. marinum ESX-1 could play a direct role in producing p

69 In this study, we have examined nine M. marinum ESX-1 mutants and the wild type by using fluo

70 se on macrophages: macrophages infected with M. marinum-expressing PGL-1 also damage axons.

71 nal similarities between M. tuberculosis and M. marinum genes in this region that we designate extRD1

72 ructed a library of 200-1000 bp fragments of M. marinum genomic DNA inserted upstream of a promoterle

73 ed by other methods, 9 were PCR positive for M. marinum group species, 8 were IHC positive, and 3 wer

74 We demonstrate here that M. marinum grows within Dictyostelium discoideum cells,

75 M. marinum has become an important model system for the

76 An unusual clade of M. marinum has been reported from fish in the Red and Me

77 M. marinum hemolysis is a proxy for phagolytic activity.

78 vo regulation of M. tuberculosis genes whose M. marinum homologs are induced in chronically infected

79 Disruption of the M. marinum homologue of Rv3881c, not previously implicat

80 owever, our results show that, although anti-M. marinum immune responses between tadpoles and adults

81 LOS pattern and that the LOS pathway used by M. marinum in macrophages is conserved during infection

82 5 displayed synergism with isoniazid against M. marinum in murine macrophages, whereas # 5175552 sign

83 Solna, Sweden) to susceptibility testing of M. marinum in order to assess the activities of eight an

84 hat ESX-5a is important for the virulence of M. marinum in the zebrafish model.

85 se cells as well as the effects on growth of M. marinum in these cells.

86 ning M. avium, M. fortuitum, M. gordonae, or M. marinum incubated with various concentrations of cipr

87 ty for the large-scale longitudinal study of M. marinum-induced tuberculosis in adult zebrafish where

88 We provide evidence that M. marinum induces membrane pores approximately 4.5 nm i

89 ed that metabolism is profoundly affected in M. marinum-infected flies.

90 of zebrafish embryos to image the events of M. marinum infection in vivo.

91 We previously developed a zebrafish embryo-M. marinum infection model to study host-pathogen intera

92 Consequently, M. marinum infection of mammals is restricted largely to

93 We examined organs of frogs with chronic M. marinum infection using transmission electron microsc

94 ag1 mutant zebrafish are hypersusceptible to M. marinum infection, demonstrating that the control of

95 aining protein, IipA, in the pathogenesis of M. marinum infection.

96 ation is systemically reduced as a result of M. marinum infection.

97 the empiric drug selection for contemporary M. marinum infections and also provide evidence that the

98 zebrafish embryo infection model that allows M. marinum infections to be visualized in real-time, com

99 was used to identify cases in an outbreak of M. marinum infections.

100 We also found that M. marinum inhibits lysosomal fusion in fish monocytes,

101 M. marinum initially proliferated inside the phagocytes

102 are different, tadpoles are as resistant to M. marinum inoculation as adult frogs.

103 M. marinum inoculation triggered a robust proinflammator

104 The co-dependent secretion is required for M. marinum intracellular growth in macrophages, where th

105 fects of the mimics of their counterparts on M. marinum intracellular survival.

106 of IL-6 and IL-10 and significantly reduced M. marinum intracellular survival.

107 ed increase in transcript levels of the anti-M. marinum invariant TCR rearrangement (iValpha45-Jalpha

108 Virulent M. marinum is able to escape from the Mycobacterium-cont

109 By reconstituting these cells, we find that M. marinum is able to use either WASP or N-WASP to induc

110 M. marinum is closely related to M. tuberculosis, which

111 M. marinum is closely related to the Mycobacterium tuber

112 In fibroblasts lacking both WASP and N-WASP, M. marinum is incapable of efficient actin polymerizatio

113 Actin tail formation by M. marinum is markedly reduced in macrophages deficient

114 and cathepsin D comparable to those for the M. marinum isolate.

115 emonstrate the best in vitro potency against M. marinum isolates to be as follows (rank order): trime

116 A population of vesicles that contained live M. marinum labeled with the lysosomal glycoprotein LAMP-

117 M. marinum lacking the mag24 gene were less virulent, as

118 We conclude that M. marinum, like M. tuberculosis, can circumvent the hos

119 d were associated with significantly reduced M. marinum loads.

120 We too find ESX-1 of M. tuberculosis and M. marinum lyses host cell membranes.

121 d in whole-cell extracts of M. tuberculosis, M. marinum, M. bovis, and M. bovis BCG, but this activit

122 M. fortuitum, M. marinum, M. scrofulaceum, M. avium, and M. chelonae g

123 These observations demonstrate that the M. marinum mel2 locus plays a role in resistance to ROS

124 Furthermore, the M. marinum melF mutant displays a defect at late stages

125 logical and infection assays showed that the M. marinum mimG mutant, an Rv3242c orthologue in a patho

126 In order to advance the utility of the M. marinum model, we have developed efficient transposon

127 We found that an M. marinum mutant with mutation of the first gene in the

128 M. marinum mutants in genes homologous to Rv3866-Rv3868

129 The M. marinum mutants showed decreased virulence in vivo an

130 s used to identify the loci responsible, and M. marinum mutants were constructed in the genes involve

131 M. marinum mutants with mutations in mel(1) and mel(2),

132 is homologues complemented the corresponding M. marinum mutants, emphasizing the functional similarit

133 In contrast to M. ulcerans and conventional M. marinum, mycolactone F-producing mycobacteria are inc

134 We have also determined the structure of M. marinum NAT in complex with CoA, shedding the first l

135 ingly, the principal CoA recognition site in M. marinum NAT is located some 30 A from the site of CoA

136 Depending on the dose of M. marinum organisms administered, an acute or chronic d

137 ly with doses between 10(2) and 10(9) CFU of M. marinum organisms.

138 identified genes expressed specifically when M. marinum persists within granulomas.

139 M. tuberculosis (and M. marinum) PGL promotes bacterial spread to growth-perm

140 onocytic cells from fish, a natural host for M. marinum, provide an extremely valuable model for the

141 ted in enhanced intracellular replication of M. marinum relative to the control wild-type strain.

142 e-like T (iT) cells in host defenses against M. marinum remain unclear.

143 with essential genes of M. tuberculosis and M. marinum, respectively.

144 Furthermore, adult anti-M. marinum responses induced active granuloma formation

145 dentified 22 gene products from the wildtype M. marinum secretome in a single CZE-tandem mass spectro

146 In this study, we have examined the M. marinum secretomes and identified four proteins speci

147 ish tank water, in which case infection with M. marinum should be considered.

148 kin biopsy can lead to improved diagnosis of M. marinum SSTIs compared to relying solely on mycobacte

149 An M. marinum strain bearing a transposon-insertion between

150 port an infection caused by a drug-resistant M. marinum strain in an otherwise healthy patient.

151 hat zebrafish are exquisitely susceptible to M. marinum strain M.

152 The DeltambtK M. marinum strain was attenuated in macrophage and Galle

153 We identified a noncytotoxic M. marinum strain with a transposon insertion in a predi

154 hat the loss of WhiB6 resulted in a virulent M. marinum strain with reduced ESX-1 secretion.

155 utant, an Rv3242c orthologue in a pathogenic M. marinum strain, was strongly attenuated in adult zebr

156 Mutation of two PE-PGRS genes produced M. marinum strains incapable of replication in macrophag

157 ere decreased, and WhiB6 was not detected in M. marinum strains lacking genes encoding ESX-1 componen

158 type and the complemented DeltamimG:Rv3242c M. marinum strains showed prominent pathological feature

159 ampin was only marginally active against the M. marinum strains tested (MIC90, at the National Commit

160 We generated M. marinum strains with deletions in conserved NAT genes

161 Characterizing a collection of M. marinum strains with in-frame deletions in each of th

162 Together, these data demonstrate that M. marinum subversion of host actin polymerization is mo

163 ing that this gene plays additional roles in M. marinum survival in the host.

164 In addition, M. marinum survives and replicates in fish monocytes whi

165 model for the three-dimensional structure of M. marinum TesA (TesAmm) and demonstrate that a Ser-to-A

166 ptible and elicit weaker immune responses to M. marinum than adults.

167 ic subset of proteins in M. tuberculosis and M. marinum that are important for bacterial virulence of

168 M. marinum that polymerized actin were free in the cytop

169 re results, 11 of 27 (41%) were positive for M. marinum; the remainder showed no growth.

170 and mel(2) are important for the ability of M. marinum to infect host cells.

171 entified two loci that affect the ability of M. marinum to infect macrophages, designated mel(1) and

172 developed an in vitro model for the study of M. marinum virulence mechanisms using the carp monocytic

173 erp-deficient M. marinum was growth attenuated in cultured macrophage

174 , a novel locus required for ESX-1 export in M. marinum was identified outside the RD1 locus.

175 M. marinum was isolated from his bone marrow.

176 vidence for cell-to-cell spread by wild-type M. marinum was obtained by microscopic detection in macr

177 Intracellular growth of M. marinum was shown to mimic the properties previously

178 erium tuberculosis and Mycobacterium leprae, M. marinum was shown to possess a closely linked and div

179 Four reference strains of M. marinum were tested on five occasions with eight drug

180 ignificantly higher than that induced by the M. marinum wild-type (WT) strain or by the M. marinum De

181 They also suggest that M. marinum will be useful as a model system for studying

182 may be involved in the early interactions of M. marinum with macrophages.