ライフサイエンスコーパス: M. abscessus

1 cterium avium complex (MAC) and 69 (36%) for M. abscessus.

2 s observed in M. marinum and the smallest in M. abscessus.

3 f mycobacteria including M. tuberculosis and M. abscessus.

4 isotopic shifts from incorporation of 15N in M. abscessus.

5 nogenum varied from those of M. chelonae and M. abscessus.

6 5 isolates of M. chelonae and 25 isolates of M. abscessus.

7 not distinguish Mycobacterium chelonae from M. abscessus.

8 gene sequencing to identify M. chelonae and M. abscessus.

9 rentiate M. immunogenum from M. chelonae and M. abscessus.

10 gesting that this clone is a subgroup within M. abscessus.

11 acterial species Mycobacterium fortuitum and M. abscessus.

12 The isolates were later identified as M. abscessus.

13 presence of global transmission networks of M. abscessus.

14 BA, to detect and localize infections due to M. abscessus.

15 can reliably identify cross-transmission in M. abscessus.

16 lturing of the explanted lung did not detect M. abscessus.

17 ne transporter required for pathogenicity in M. abscessus.

18 ty of a series of indolecarboxamides against M. abscessus.

19 PL, occur during chronic lung infection with M. abscessus.

20 combination works synergistically to inhibit M. abscessus.

21 the erm(41) genotype is a useful adjunct for M. abscessus.

22 suitable to test antibiotic activity against M. abscessus.

23 ne showed promising in vivo activity against M. abscessus.

24 ne derivatives exhibit lower MIC(90) values (M. abscessus: 0.78 muM), and the sulfoxides show higher

25 ical isolates identified 2 clonal strains of M. abscessus; 1 clone was isolated from water sources at

26 haracterized clinical isolates comprising 29 M. abscessus, 15 M. massiliense, and 2 M. bolletii isola

27 are complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%).

28 M. abscessus (34%) and M. avium complex (83%) were the m

29 ) for rapidly growing mycobacteria (98% were M. abscessus), 78% (29 of 37) for M. kansasii, and 26% (

30 dividuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leadi

31 nt the 2.9- angstrom resolution structure of M. abscessus AftD, determined by single-particle cryo-el

32 nce strain, independent clinical isolates of M. abscessus also readily establish infection and prolif

33 ggests that person-to-person transmission of M. abscessus among CF patients is indeed rare and reinfo

34 A total of 82 isolates (58 M. abscessus and 24 M. chelonae isolates) were tested bl

35 methods, 46 of the isolates were found to be M. abscessus and 29 were identified as M. chelonae.

36 erm(41) sequencing of 285 M. abscessus and 45 M. chelonae isolates was compared to

37 tial sequencing) is required for division of M. abscessus and closely related species.

38 s previously identified as being M. chelonae/M. abscessus and identified M. massiliense from isolates

39 ting of M. fortuitum against clarithromycin; M. abscessus and M. chelonae against the aminoglycosides

40 hould be able to easily identify isolates of M. abscessus and M. chelonae.

41 nt may be helpful for distinguishing between M. abscessus and M. chelonae.

42 uberculosis as well as against intracellular M. abscessus and M. leprae, indicating their potential a

43 ) genome, regions that discriminated between M. abscessus and M. massiliense were identified through

44 and three pairs of closely related strains: M. abscessus and M. massiliense, M. mucogenicum and M. p

45 ompounds exhibit activity against planktonic M. abscessus and M. tuberculosis as well as against intr

46 an target DosS-mediated hypoxic signaling in M. abscessus and recapitulate the phenotypic effects of

47 or healthcare-associated transmission in two M. abscessus and two M. avium clusters.

48 engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most

49 nchoscopes and endoscopic cleaning machines (M. abscessus) and contaminated hospital water supplies (

50 large number of changes in the physiology of M. abscessus, and its interactions with innate immune ce

51 submitted as M. chelonae were identified as M. abscessus, and one isolate submitted as M. abscessus

52 ous mycobacteria (NTM), such as M. avium and M. abscessus, and several Gram-positive bacteria, includ

53 Two colony-variants of M. abscessus are routinely isolated from CF samples, smo

54 e cholesterol and 4-AD catabolic pathways of M. abscessus are unique in that they converge upstream o

55 ithmetic mean = 1.5% of hsp65 sequences) and M. abscessus (arithmetic mean = 0.006% of hsp65 sequence

56 s bactericidal activity (99% inactivation of M. abscessus at 12.5 muM), while they are not cytotoxic

57 ere introduced in the isogenic background of M. abscessus ATCC 19977 and the resulting strains probed

58 However, M. abscessus ATCC 19977 harbors two hsaD homologs elsewh

59 Based on the M. abscessus ATCC 19977(T) genome, regions that discrimi

60 ighly effective at preventing infection with M. abscessus because it is a ubiquitous environmental sa

61 how the direct competitive inhibition of the M. abscessus beta-lactamase, Bla(Mab), using a novel ass

62 iary and cough clearance, we identified that M. abscessus biofilms may be more resistant to mechanica

63 Thus, the mechanical properties of M. abscessus biofilms may contribute to the persistent n

64 or subcutaneously significantly reduced lung M. abscessus burden.

65 annot be used to infer cross-transmission in M. abscessus but does provide enough information to repl

66 red rifabutin to enhance its potency against M. abscessus by blocking intrabacterial inactivation and

67 ndistinguishable from Mycobacterium chelonae/M. abscessus by partial 16S rRNA gene sequencing.

68 This demonstrates that the inability to type M. abscessus by PFGE is associated with a single clone o

69 fit of using thiourea-containing buffer with M. abscessus by studying 69 isolates not previously type

70 val during infection with asparagine-limited M. abscessus can be attributed to alterations in unpaire

71 M. abscessus can transition between a noninvasive, biofi

72 cases (57%; odds ratio = 0.7, P < 0.05) and M. abscessus cases (51%; odds ratio = 0.5, P < 0.01) tha

73 peptidolipid in the outermost portion of the M. abscessus cell wall masks underlying cell wall lipids

74 rodrug with narrow-spectrum activity against M. abscessus-chelonae complex species.

75 ccurs through TPP loss by mutation, and some M. abscessus clinical isolates are naturally phage-insen

76 icacy of this combination against a panel of M. abscessus clinical isolates, revealing the therapeuti

77 or antibacterial activity against a panel of M. abscessus clinical isolates, were highly bactericidal

78 l viability and showed enhanced effects on a M. abscessus clinical strain when combined with amikacin

79 One M. abscessus cluster possibly had common acquisition ari

80 Individuals comprising one M. abscessus cluster, with no plausible healthcare-assoc

81 this provides an explanation whereby initial M. abscessus colonization of abnormal lung airways escap

82 e sequencing (26 isolates of the M. chelonae-M. abscessus complex and 64 remaining isolates, includin

83 erol and 4-AD catabolic gene clusters of the M. abscessus complex lack genes encoding HsaD, the meta-

84 methods differentiate between members of the M. abscessus complex.

85 However, after two months, M. abscessus counts increased as the patient mounted a r

86 susceptibility by overexpressing Bla(Mab) in M. abscessus, demonstrating relebactam-Bla(Mab) target e

87 lebactam, in combination with the front line M. abscessus drug imipenem.

88 neutrophils treated with azithromycin killed M. abscessus equally as well as untreated neutrophils fr

89 The DeltahsaD mutant of M. abscessus excreted cholesterol metabolites with a ful

90 drug susceptibility testing, all isolates of M. abscessus exhibited resistance to tobramycin (MIC of

91 M. abscessus exists as either a glycopeptidolipid (GPL)

92 Conversely, M. abscessus expressing GPL does not stimulate expressio

93 Blood cultures grew M. abscessus for all patients, and admission peripheral

94 The release of M. abscessus from apoptotic macrophages initiated the fo

95 ory-confirmed colonization or infection with M. abscessus from January 2013 through December 2015.

96 Isolates of M. abscessus from sputum do not always reflect the entir

97 on is facilitated by biofilm formation, with M. abscessus glycopeptidolipids playing an important rol

98 Consistent with this prediction, M. abscessus grew on both steroids.

99 rates efficiently, and a DeltahsaD mutant of M. abscessus grew on neither steroid.

100 the M. avium complex (MAC), the M. chelonae-M. abscessus group (MCAG), the M. fortuitum group (MFG),

101 m abscessus (M. abscessus sensu lato, or the M. abscessus group) comprises three closely related taxa

102 ification within 24 h after isolation of the M. abscessus group.

103 Biotin cofactor synthesis was required for M. abscessus growth due to increased intracellular bioti

104 , including M. immunogenum, M. chelonae, and M. abscessus, have been associated with nosocomial infec

105 which is a major virulence factor that makes M. abscessus highly cytotoxic to mouse macrophages, and

106 between the smooth and rough morphotypes of M. abscessus However, in cystic fibrosis neutrophils, wo

107 cent evidence of within-patient subclones of M. abscessus in adults with CF suggests the possibility

108 d markers of a successful phage treatment of M. abscessus in advanced lung disease.

109 As the pathogenic mechanisms of M. abscessus in the context of the lung are not well-und

110 The mutants further differed from wild-type M. abscessus in their ability to replicate and induce in

111 potent inhibitors and adjunct inhibitors of M. abscessus in vivo offers repurposing opportunities th

112 The incidence rate of M. abscessus increased from 0.7 cases per 10000 patient-

113 Azithromycin did not affect M. abscessus-induced neutrophil reactive oxygen species

114 phosphate (ABL/PI5P) were tested in vitro in M. abscessus-infected macrophages from PWCF as potential

115 of cording in the in vivo physiopathology of M. abscessus infection and emphasizes cording as a mecha

116 We developed a mouse model of pulmonary M. abscessus infection using the aerosolized route of in

117 es from nine non-CF patients with persistent M. abscessus infection were characterized by colony morp

118 he 3 drugs usually combined for treatment of M. abscessus infection, cefoxitin was the most active be

119 Alternative routes of acquisition of M. abscessus infection, in particular the environment, r

120 ) demonstrated efficacy in a murine model of M. abscessus infection.

121 provide therapeutic targets for treatment of M. abscessus infection.

122 rt a prospective advance in the treatment of M. abscessus infection; increasing the susceptibility of

123 unity, but the transplants did not clear the M. abscessus infections and both patients died as a resu

124 nical isolates, we show that the majority of M. abscessus infections are acquired through transmissio

125 acteria-specific diagnostic to differentiate M. abscessus infections from underlying pulmonary diseas

126 Conventional imaging cannot distinguish M. abscessus infections from underlying pulmonary diseas

127 nd effective adjunct for managing refractory M. abscessus infections in immunocompromised individuals

128 ited chemical structure class active against M. abscessus infections with promising translational dev

129 The same has been observed for M. abscessus infections, which are very difficult to tre

130 h immunomodulatory effects, is used to treat M. abscessus infections.

131 here is still conflicting evidence as to how M. abscessus is acquired and whether cross-transmission

132 ng direct patient-to-patient transmission of M. abscessus is critically important in directing an inf

133 he differentiation of these two species from M. abscessus is difficult and relies on the sequencing o

134 ggests healthcare-associated transmission of M. abscessus is rare and includes a report of potential

135 It appears that M. abscessus is transported to the CNS within macrophage

136 of 1,279 (143-134) SNVs between all Ontario M. abscessus isolates and 2,908 (21-3,204) single nucleo

137 ng activity in vitro against a wide panel of M. abscessus isolates and in infected macrophages.

138 ormed whole-genome sequencing of 11 clinical M. abscessus isolates derived from eight U.S. patients w

139 ole-genome sequencing data demonstrated that M. abscessus isolates from 16 patients were unrelated, d

140 pectively sequenced the whole genomes of 145 M. abscessus isolates from 62 patients, seen at 4 hospit

141 The M. abscessus isolates from case patients and the supplem

142 Whole-genome sequencing was applied to 27 M. abscessus isolates from the 20 patients in this cohor

143 M. abscessus isolates pre and post-phage treatment demon

144 Previous population studies of clinical M. abscessus isolates utilized multilocus sequence typin

145 ins and 145 clinical isolates (58 MAC and 87 M. abscessus isolates), including 54 clarithromycin- and

146 led to the unambiguous identification of 26 M. abscessus isolates, 7 M. massiliense isolates, and 2

147 at variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage iden

148 ity testing by Etest of four carbapenems for M. abscessus isolates.

149 limited by a lack of WGS from environmental M. abscessus isolates.

150 accurate erm(41) genotype results for all 87 M. abscessus isolates.

151 gordonae, and 5 M. chelonae group (all were M. abscessus) isolates.

152 d and mitigated a 2-phase clonal outbreak of M. abscessus linked to hospital tap water.

153 berculosis treatment, their efficacy against M. abscessus lung disease is severely compromised by int

154 e four-drug combination in a murine model of M. abscessus lung infection.

155 a rough, wild-type human clinical isolate of M. abscessus (M. abscessus-R) and a smooth, attenuated m

156 n M. tuberculosis, the opportunistic strains M. abscessus, M. marinum and M. avium, and the nonpathog

157 1) PCR for straightforward identification of M. abscessus, M. massiliense, and M. bolletii and the as

158 cation and typing of 42 clinical isolates of M. abscessus, M. massiliense, and M. bolletii from patie

159 ve PCR-based method for distinguishing among M. abscessus, M. massiliense, and M. bolletii.

160 solates with ambiguous species identities as M. abscessus-M. massiliense by rpoB, hsp65, and secA seq

161 d overscores resistance and that isolates of M. abscessus/M. chelonae from CF patients are more likel

162 incidence of pulmonary infections caused by M. abscessus (MAB) is on rise globally.

163 Insight into the immune control of M. abscessus may provide novel targets of therapy.

164 stitutions in their tail spike proteins, and M. abscessus mutants resistant to TPP-independent phages

165 mutations on the physiology and virulence of M. abscessus, mutations were introduced in the isogenic

166 gs were characterized in a MIC assay against M. abscessus, Mycobacterium intracellulare, Mycobacteriu

167 were used to identify 75 isolates as either M. abscessus or M. chelonae that were originally submitt

168 e to Mycobacterium avium, M. intracellulare, M. abscessus, or M. massiliense and three healthy contro

169 erculosis, is completely ineffective against M. abscessus, partially due to the presence of an ADP-ri

170 Overall, M. abscessus phenotype changes overtime influenced by mu

171 nsiderable time on the same wards with other M. abscessus-positive patients.

172 We studied 118 strains of M. abscessus previously studied by PFGE by randomly ampl

173 is demonstrates that asparagine transport in M. abscessus prior to infection is not required for repl

174 aphy (PET) was performed in a mouse model of M. abscessus pulmonary infection and in a patient with m

175 lows for initial proliferation and sustained M. abscessus pulmonary infection and permits evaluation

176 Dynamic (11)C-PABA PET in a mouse model of M. abscessus pulmonary infection rapidly distinguished i

177 tic fibrosis and microbiologically confirmed M. abscessus pulmonary infection was safe and demonstrat

178 n a patient with microbiologically confirmed M. abscessus pulmonary infection.

179 observed that the increased virulence of the M. abscessus R variant compared with the S variant corre

180 oblast-mycobacterium microcolony assay, with M. abscessus-R exhibiting growth characteristics similar

181 ear phagocyte aggregates develop at sites of M. abscessus-R infection, but are absent with M. abscess

182 We have found that M. abscessus-R is able to persist and multiply in a muri

183 M. abscessus-R is able to persist and multiply in human

184 M. abscessus-R resides in a phagosome typical for pathog

185 type human clinical isolate of M. abscessus (M. abscessus-R) and a smooth, attenuated mutant (M. absc

186 the metabolism and accumulation of PABA into M. abscessus reference and clinical isolates.

187 Recently, two new M. abscessus-related species, M. massiliense and M. boll

188 FF-NH(2) leverages intrinsic M. abscessus resistance conferred by the transcription f

189 The M. abscessus rough (R) variant, devoid of cell-surface g

190 ly reported for virulent M. tuberculosis and M. abscessus-S exhibiting growth characteristics similar

191 . abscessus-R infection, but are absent with M. abscessus-S infection.

192 rsist and multiply in human monocytes, while M. abscessus-S is deficient in this ability.

193 In contrast, M. abscessus-S resides in a "loose" phagosome with the p

194 conclude that a mutation has occurred in the M. abscessus-S variant which has altered the ability of

195 bscessus-R) and a smooth, attenuated mutant (M. abscessus-S) which spontaneously dissociated from the

196 ine pulmonary infection model in contrast to M. abscessus-S, which is rapidly cleared.

197 Mycobacterium abscessus (M. abscessus sensu lato, or the M. abscessus group) comp

198 taxonomic statuses are under revision, i.e., M. abscessus sensu stricto, Mycobacterium bolletii, and

199 Mycobacterium immunogenum, M. chelonae, and M. abscessus, showed various susceptibilities to the glu

200 nous administration was safe and reduced the M. abscessus sputum load tenfold within one month.

201 ium abscessus subspecies (ssp.) abscessus, 1 M. abscessus ssp.

202 study we demonstrate that rough variants of M. abscessus stimulate the human macrophage innate immun

203 ts to the lung environment, pure colonies of M. abscessus strain 19,977 were grown in 7H9 broth with

204 e report herein the draft genome sequence of M. abscessus strain 47J26.

205 vatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering

206 We found that patients acquired unique M. abscessus strains even after spending considerable ti

207 y explores the genomic diversity of clinical M. abscessus strains from multiple continents and provid

208 PD-PCR can be used for genetic comparison of M. abscessus strains, including strains which cannot be

209 We tested 100 M. abscessus strains, synthetic mixes with different sus

210 accurate approach for discriminating MAC and M. abscessus (sub)species and for detecting clarithromyc

211 The accuracies of MAC and M. abscessus (sub)species identification were 92.1% (35/

212 from a large hospital-associated outbreak of M. abscessus subsp.

213 onmental acquisition of outbreak isolates of M. abscessus subsp.

214 Environmental M. abscessus subsp.

215 nalyzed the core and accessory genomes of 26 M. abscessus subsp.

216 ial species that comprises three subspecies: M. abscessus subsp.

217 al B-lactam combinations in the treatment of M. abscessus subsp.

218 We conclude that successful investigation of M. abscessus subsp.

219 acterium abscessus subsp. bolletii (n = 24), M. abscessus subsp. abscessus (n = 6), Mycobacterium for

220 he tedizolid MIC90 values for 81 isolates of M. abscessus subsp. abscessus and 12 isolates of M. absc

221 icated the presence of two clonal groups for M. abscessus subsp. abscessus and five clonal groups for

222 larithromycin susceptibility breakpoints for M. abscessus subsp. abscessus be changed from </=2 to </

223 on the usefulness of macrolides for treating M. abscessus subsp. abscessus infections.

224 scessus subsp. massiliense and 15% to 20% of M. abscessus subsp. abscessus isolates renders these spe

225 of closely related U.S. and Western European M. abscessus subsp. abscessus isolates that are genetica

226 Sequencing of the erm gene of M. abscessus subsp. abscessus will predict inducible mac

227 eating approximately 20% of U.S. isolates of M. abscessus subsp. abscessus.

228 . peregrinum and a nonfunctional erm gene in M. abscessus subsp. massiliense and 15% to 20% of M. abs

229 obacterium abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates identified by w

230 bscessus subsp. abscessus and 12 isolates of M. abscessus subsp. massiliense were 8 mug/ml and 4 mug/

231 All 50 isolates were typed as M. abscessus subspecies abscessus and were clonally rela

232 oped invasive, extrapulmonary infection from M. abscessus subspecies abscessus in an outbreak setting

233 7 patients with VAD developed extrapulmonary M. abscessus subspecies abscessus infection.

234 d highly accurate method to both distinguish M. abscessus subspecies and to determine which strains a

235 have limited diagnostic tools to distinguish M. abscessus subspecies, and the testing for macrolide r

236 ncreased cell envelope fluidity and promoted M. abscessus survival in the alkaline lung environment.

237 patients with genetically related strains of M. abscessus that had been previously typed by variable-

238 le-genome sequencing (WGS) on 32 isolates of M. abscessus that were taken from multiple body sites of

239 of patients in this study have not acquired M. abscessus through direct patient-to-patient transmiss

240 nce and spread of the environmental organism M. abscessus through the global cystic fibrosis populati

241 11)C-PABA was intracellularly metabolized by M. abscessus to (11)C-7,8-dihydropteroate.

242 ms in embC may be a rapid, one-step, way for M. abscessus to generate broad-spectrum diversity benefi

243 isruption of dosRS impairs the adaptation of M. abscessus to hypoxia, resulting in decreased bacteria

244 The intrinsic resistance of M. abscessus to most commonly available antibiotics seri

245 Using RNA-seq, we show that exposure of M. abscessus to sublethal doses of RIF and Rifabutin (RB

246 g evolutionary pressure during adaptation of M. abscessus to the human lung is embC which encodes an

247 th smear patterns were identical to those of M. abscessus type strain ATCC 19977, which had a nonsmea

248 Both M. abscessus variants also have distinctive growth patte

249 that respiratory epithelial cells respond to M. abscessus variants lacking GPL with expression of IL-

250 These studies increase our understanding of M. abscessus virulence and of neutrophil mycobactericida

251 ur findings and discover clinically relevant M. abscessus virulence factors including a secretion sys

252 s M. abscessus, and one isolate submitted as M. abscessus was found to be M. chelonae.

253 Overall, the genetic diversity of M. abscessus was large, with a median pairwise distance

254 Previously, M. abscessus was thought to be independently acquired by

255 only in M. chelonae), and cefoxitin (only in M. abscessus) was shown.

256 Mycobacterium abscessus (M. abscessus) was the species most likely to cause clini

257 utes a significant resistance determinant in M. abscessus We demonstrate that mycobacterial HflX asso

258 er Mycobacterium species -- M. smegmatis and M. abscessus -- we demonstrate a striking conservation o

259 h incident NTM infections from either MAC or M. abscessus were less likely to have had chronic azithr

260 Several bacterial species, including M. abscessus, were cultured from an opened multidose sup

261 Five outbreaks due to M. abscessus which gave broken DNA by PFGE gave evaluabl

262 onvolute and quantitate mixed populations of M. abscessus with different clarithromycin resistance tr

263 ell as co-occurrence of mixed populations of M. abscessus with different susceptibility profiles.

264 have not demonstrated cross-transmission of M. abscessus within our hospital, except between 1 sibli