ライフサイエンスコーパス: C. difficile

1 icile, and therefore prevented the growth of C. difficile.

2 ngal infections, Pseudomonas infections, and C. difficile.

3 ategies to target the most severe strains of C. difficile.

4 drugs set V library (114 compounds), against C. difficile.

5 her screened against 20 clinical isolates of C. difficile.

6 .4% of ICU patients asymptomatically carried C. difficile.

7 ical tools for studying the pathogenicity of C. difficile.

8 om 3 to 800 muM against clinical isolates of C. difficile.

9 ts with underlying IBD who test positive for C. difficile.

10 impacts the proportion of CmrRST-expressing C. difficile.

11 an effective component in a vaccine against C. difficile.

12 ents who are asymptomatically colonized with C. difficile.

13 get upregulated in response to hypervirulent C. difficile.

14 icity of PPEP-1 from the common gut pathogen C. difficile.

15 damage and fermentation products produced by C. difficile.

16 the loss of colonization resistance against C. difficile.

17 for both) and outpatients (norovirus: 10.7%; C. difficile: 10.5%).

18 etected among inpatients (cases vs controls: C. difficile, 18.8% vs 8.4%; norovirus, 5.1% vs 1.5%; p<

19 on was highest among outpatients (AGE: 2715; C. difficile: 285; norovirus: 291) and inpatients >=65 y

20 as9 was used to sequentially remove from the C. difficile 630 reference strain (NCTC 13307) two ermB

21 91) and inpatients >=65 years old (AGE: 459; C. difficile: 91; norovirus: 26).

22 and experienced highly variable patterns of C. difficile abundance, where increased shedding over sh

23 Species protecting against hospital-related C. difficile acquisition included Gemmiger spp., Odoriba

24 cci were associated with a decreased risk of C. difficile acquisition.

25 ICU MRSA and C. difficile acquisitions per 1000 patients decreased be

26 nd 2016 (MRSA acquisitions, 25.4 to 4.1; and C. difficile acquisitions, 11.1 to 3.5), whereas VRE acq

27 Moreover, it maintained its anti-C. difficile activity after being exposed to SGF and SIF

28 WPs) were identified that were implicated in C. difficile adhesion and colonization.

29 ICU MRSA & C. difficile admissions & acquisitions per 1000 patients

30 sions 38.8 to 13.1; acquisitions 25.4 to 4.1;C. difficile admissions 10.6 to 4.2; acquisitions 11.1 t

31 logen substitutions, which afforded new anti-C. difficile agents with ultrapotent activities [MICs as

32 s and 2% died; 3 deaths were associated with C. difficile and 1 with norovirus.

33 t the activity of aryl-alkyl-lysines against C. difficile and associated pathogens.

34 shown to elicit protective immunity against C. difficile and is under consideration as a possible va

35 nderstanding of its genome, the epigenome of C. difficile and its functional impact has not been syst

36 resistant bacteria with a virulent strain of C. difficile and monitored colonization and pathogenesis

37 C. difficile and norovirus were detected year-round with

38 C. difficile and norovirus were leading AGE pathogens in

39 wn about the host humoral immune response to C. difficile and TcdB during primary and recurrent infec

40 gh level of peptidoglycan N-deacetylation in C. difficile and the consequent resistance to lysozyme.

41 hicillin-resistant S. aureus, P. aeruginosa, C. difficile, and fungal infections all had high prevale

42 compared with well-characterised strains of C. difficile, and loss of the phage protection protein C

43 nate, a crucial metabolite for the growth of C. difficile, and therefore prevented the growth of C. d

44 rk for development of a mechanistic class of C. difficile antitoxins.

45 ectively collected data on colonization with C. difficile are largely unavailable.

46 ing active CDI from asymptomatic carriage of C. difficile are not well understood.

47 ve study, we evaluated the FDA-cleared Aries C. difficile assay and compared its performance and work

48 he cobas Cdiff assay compared with the Xpert C. difficile assay was 98.0% (100/102; 95% confidence in

49 tion test (NAAT; BD MAX Cdiff assay or Xpert C. difficile assay) and Singulex Clarity C. diff toxins

50 robiota interactions in the manifestation of C. difficile-associated disease.

51 We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disrupt

52 ease analysis (REA) BI and non-BI strains of C. difficile at study entry.

53 To detect the phenotype of germinated C. difficile bacteria, we utilize its characteristically

54 s of laxatives, more individuals experienced C. difficile blooms.

55 e, and 234 (77.5%) samples were negative for C. difficile by all three testing methods.

56 a modified cell cytotoxicity assay, isolated C. difficile by anaerobic culture, and performed PCR rib

57 Although C. difficile can be an asymptomatic colonizer, its patho

58 We identified asymptomatic C. difficile carriage among 1897 ICU patients, using rec

59 thm, the samples were tested with PCR (Xpert C. difficile; Cepheid), and chart review was performed.

60 1 was not found in its entirety in any other C. difficile clade, or indeed, in any other microbial ge

61 surpassed the activity of vancomycin against C. difficile clinical isolates.

62 clinically observed resistance of infants to C. difficile colitis.

63 WGS using an Illumina MiSeq instrument on 8 C. difficile colonies randomly selected from each cultur

64 ata of the human gut microbiome, we detected C. difficile colonization and blooms in people recoverin

65 Serological sequelae of infant C. difficile colonization are poorly understood.

66 tinal disturbances, but this relationship to C. difficile colonization has never been tested directly

67 Asymptomatic C. difficile colonization is believed to predispose to s

68 o distinguish clinical CDI from asymptomatic C. difficile colonization.

69 ealthcare settings, and higher prevalence of C. difficile colonization.

70 rom those with non-C. difficile diarrhea and C. difficile colonization.

71 abolic pathway in patients who later acquire C. difficile colonization.

72 diarrhoeal events trigger susceptibility to C. difficile colonization.

73 Because a single C. difficile colony is selected from culture for WGS, si

74 The mechanisms underlying C. difficile community formation and inter-bacterial int

75 ve differential functions or requirements in C. difficile compared to other spore formers.

76 In order to understand if LuxS mediates C. difficile crosstalk with other gut species, C. diffic

77 hough uncommon for transcription regulators, C. difficile DdlR is essential, as the ddlR null mutant

78 cal stool specimens for detection of tcdB in C. difficile, demonstrated acceptable sensitivity and sp

79 nguish patients with CDI from those with non-C. difficile diarrhea and C. difficile colonization.

80 ble to distinguish between patients with non-C. difficile diarrhea and C. difficile infection, and to

81 The most common non-C. difficile diarrheal pathogens in the post-GI PCR coho

82 The most common non-C. difficile diarrheal pathogens in the post-GI PCR coho

83 zing antibody response and protected against C. difficile disease in a mouse model.

84 Here, we used a murine model of C. difficile disease recurrence to demonstrate that an i

85 egatively impacts sporulation, a key step in C. difficile disease transmission, and these results are

86 In a hamster model of acute C. difficile disease, the CmrRST system is required for

87 izing TcdB toxin, the primary determinant of C. difficile disease.

88 Investigation of the C. difficile DNA sequence revealed the presence of cell

89 ical practice of testing for the presence of C. difficile during acute IBD exacerbations.

90 Our findings indicate that C. difficile employs phase variation of the CmrRST signa

91 d to compare clinical characteristics, Xpert C. difficile/Epi (PCR) cycle threshold (C(T) ), and Sing

92 stics to those of the BD Max Cdiff and Xpert C. difficile/Epi assays.

93 urine, a covalent conjugate of a distinctive C. difficile fermentation product (isocaproate) and an a

94 owth of commensal bacteria that compete with C. difficile for the nutritional niche.

95 rsus that of spore aggregates and non-viable C. difficile forms, which causes a distinctive high-freq

96 C. difficile genome analysis showed that 12 genes potent

97 t and in all of the approximately 300 global C. difficile genomes examined.

98 review summarises advances in understanding C. difficile germination and outlines current models of

99 Divergent C. difficile germination models have been proposed to ex

100 periodical monitoring included evaluation of C. difficile growth and activity of toxins TcdA and TcdB

101 We demonstrate that C. difficile growth is significantly reduced when co-cul

102 The molecular epidemiology of C. difficile has shifted, and this may have implications

103 in mediating colonization resistance against C. difficile have associated CDI with specific microbial

104 Here, we identify the C. difficile heme-sensing membrane protein system (HsmRA

105 ice infected with a high-virulence strain of C. difficile; however, significant deficits in intestina

106 nd excluding patients from stool testing for C. difficile if they have received laxatives within the

107 gainst CDI later in life afforded by natural C. difficile immunization events require further investi

108 e we present findings demonstrating that the C. difficile immunogenic lipoprotein CD0873 plays a crit

109 cile infection (stool specimens positive for C. difficile in a person >=1 year of age with no positiv

110 Efforts to reduce the spread of C. difficile in hospitals have led to the development of

111 ptomatic carriers are an active reservoir of C. difficile in the nosocomial environment.

112 hibits the life cycles of various strains of C. difficile in vitro, suggesting that the FDA-approved

113 e to restore colonization resistance against C. difficile in vivo However, the mechanism(s) by which

114 Clostridium difficile (C. difficile) incidence has tripled over the past 15 yea

115 C. difficile-induced tissue inflammation and mortality w

116 ations in stool do not differentiate between C. difficile infection (CDI) and asymptomatic carriage.

117 ences in the gut microbiota, the severity of C. difficile infection (CDI) and mortality did not diffe

118 offer an accurate, stand-alone solution for C. difficile infection (CDI) diagnostics, and further pr

119 Much of the focus on immunity during C. difficile infection (CDI) has been on type 3 immunity

120 cidence, severity, and costs associated with C. difficile infection (CDI) have increased dramatically

121 C. difficile infection (CDI) is largely caused by two vi

122 idioides difficile are at risk of developing C. difficile infection (CDI), but the factors associated

123 micin, are FDA-approved for the treatment of C. difficile infection (CDI), but these therapies still

124 s now a preferred treatment for all cases of C. difficile infection (CDI), regardless of disease seve

125 tion with an inactive TcdB fragment prevents C. difficile infection (CDI)-associated pathology.

126 to the increasing incidence and severity of C. difficile infection (CDI).

127 tion is believed to predispose to subsequent C. difficile infection (CDI).

128 iotic use (RR, 1.33; 95% CI, 1.28-1.38), and C. difficile infection (incidence rate ratio, 1.18; 95%

129 (OR, 1.62; 95% CI, 1.01-2.61; P = .046) and C. difficile infection (OR, 4.01; 95% CI, 2.21-7.59; P <

130 s (OR, 1.62; 95% CI, 1.01-2.61; p=0.046) and C. difficile infection (OR, 4.01; 95% CI, 2.21-7.59; p<0

131 ile toxins may protect against recurrence of C. difficile infection (rCDI).

132 rging Infections Program identified cases of C. difficile infection (stool specimens positive for C.

133 from 10 children (8 children diagnosed with C. difficile infection and 2 children with asymptomatic

134 The estimated national burden of C. difficile infection and associated hospitalizations d

135 es for inhibiting these processes to prevent C. difficile infection and disease recurrence.

136 tment to address the unmet needs in treating C. difficile infection and preventing its recurrence.

137 une events that follow primary and recurrent C. difficile infection and provide a compelling inverse

138 This higher incidence of C. difficile infection and recurrence is believed to be

139 emokine responses are associated with severe C. difficile infection and support a key role for intest

140 The symptoms of C. difficile infection are caused by the activity of thr

141 and protective host immune mediators against C. difficile infection are not fully understood, with da

142 timate of the burden of hospitalizations for C. difficile infection decreased by 24% (95% CI, 0 to 48

143 the adjusted estimate of the total burden of C. difficile infection decreased by 24% (95% CI, 6 to 36

144 he national burden of health care-associated C. difficile infection decreased by 36% (95% CI, 24 to 5

145 ial factors, the host immune response during C. difficile infection greatly influences disease severi

146 ng to clade 5, and are often associated with C. difficile infection in both humans and animals.

147 s suggest that CDT increases the severity of C. difficile infection in some of the most problematic c

148 The number of cases of C. difficile infection in the 10 U.S. sites was 15,461 i

149 C. difficile infection is dependent on the secretion of

150 efforts are reducing the national burden of C. difficile infection is unclear.

151 atients and results in over 400,000 cases of C. difficile infection per year.

152 c impact of aging on immune responses during C. difficile infection remains to be well described.

153 Fecal extracts from children with C. difficile infection showed increased IL-17A and T cel

154 ggest that Cwp22 is an attractive target for C. difficile infection therapeutics and prophylactics.

155 The estimated national burden of C. difficile infection was 476,400 cases (95% confidence

156 nulocyte response in aged mice during severe C. difficile infection was accompanied by a simultaneous

157 the national burden of community-associated C. difficile infection was unchanged.

158 28 months old) were rendered susceptible to C. difficile infection with the antibiotic cefoperazone

159 We leverage mechanistic modeling of C. difficile infection, a major HAI disease, to simulate

160 patients with non-C. difficile diarrhea and C. difficile infection, and to some degree, patients who

161 g weights to estimate the national burden of C. difficile infection, first recurrences, hospitalizati

162 ised patients experience a high incidence of C. difficile infection, ranging from 6% to 33% in the he

163 oised for IL-17 production were resistant to C. difficile infection, whereas elimination of gammadelt

164 y gammadelta T cells in host defense against C. difficile infection.

165 ated mouse model to assess susceptibility to C. difficile infection.

166 n attractive therapeutic target for managing C. difficile infection.

167 ellular and cytokine immune responses during C. difficile infection.

168 the development of effective agents against C. difficile infection.

169 ction, and advanced age is a risk factor for C. difficile infection.

170 non-antibiotic agent for the alleviation of C. difficile infection.

171 , were associated with reduced recurrence of C. difficile infection.

172 tyrosine import system, an amino acid key in C. difficile infection.

173 disruption of the colonic epithelium during C. difficile infection.

174 fers a very rapid alternative for diagnosing C. difficile infection.

175 increased disease severity during subsequent C. difficile infection.

176 n responsible for many of the pathologies of C. difficile infection.

177 ated with higher antibiotic use and rates of C. difficile infection.

178 ibute to host susceptibility and severity of C. difficile infection.

179 ion persistence in a murine model of relapse C. difficile infection.

180 as in the case of Clostridioides difficile (C. difficile) infection.

181 ve pyuria was associated with post-operative C. difficile infections (aOR 1.7; 1.2-2.4); risk was hig

182 ive pyuria was associated with postoperative C. difficile infections (aOR, 1.7; 95% CI, 1.2-2.4); ris

183 Recurrence of C. difficile infections among immunocompromised patients

184 Given the clinical overlap between C. difficile infections and acute IBD exacerbations (ie,

185 C. difficile infections have mortality rates of 6 to 30%

186 abdominal pain), it is hard to differentiate C. difficile infections versus colonizations in patients

187 ts (2%) diagnosed with healthcare-associated C. difficile infections, 3 (27%) had genetically related

188 ive surgical (SSI), urinary tract (UTI), and C. difficile infections.

189 that may play an important role in recurrent C. difficile infections.

190 The effects of increased C. difficile inoculum, and pre-exposure to simulated gas

191 While the knowledge on gut microbiota - C. difficile interactions has improved over the years, t

192 difficile crosstalk with other gut species, C. difficile interactions with a common gut bacterium, B

193 C. difficile is a genetically diverse species that can b

194 The S-layer in C. difficile is constructed mainly of S-layer protein A

195 l disturbances, our results help explain why C. difficile is frequently detected as a co-infecting pa

196 genic bacteria, a lack of N-deacetylation in C. difficile is not linked to a decrease in virulence.

197 Spore germination in C. difficile is regulated by the detection of bile salt

198 examined within-host genetic diversity among C. difficile isolates collected from children.

199 ults highlight the regional differences that C. difficile isolates display, being in this case the CO

200 C. difficile isolates from VRE swabs, and from C. diffic

201 d not result in a consistent decrease in the C. difficile life cycle in vivo, it was able to attenuat

202 Interestingly, the absence of C. difficile LuxS alleviates the B. fragilis-mediated gr

203 ole for intestinal eosinophils in mitigating C. difficile-mediated disease severity.

204 cholerae and the hydrosulphide channel from C. difficile, molecular dynamics studies showed that the

205 nized with toxigenic (TCD) and non-toxigenic C. difficile (NTCD), respectively.

206 efore stool collection) and a positive stool C. difficile nucleic acid amplification test (NAAT) were

207 efore stool collection) and a positive stool C. difficile nucleic acid amplification test were enroll

208 rocesses, factors that are conserved only in C. difficile or the related Peptostreptococcaceae family

209 t our strategy detects up to 95% of "future" C. difficile outbreaks.

210 toxin B (TcdB) and FZD receptors and perturb C. difficile pathogenesis in epithelial cells.

211 ugs, and pathogen-microbiota interactions in C. difficile pathogenesis, as well as the impact of host

212 ition to suggesting a role for bile acids in C. difficile pathogenesis, these findings provide a fram

213 Colonization of the gut is critical for C. difficile pathogenesis.

214 atients were included if they had a positive C. difficile PCR performed on an unformed stool and rece

215 010-2013, we evaluate stool toxin levels and C. difficile PCR ribotypes.

216 The C. difficile peptidoglycan is largely N-deacetylated on

217 atients were included if they had a positive C. difficile polymerase chain reaction (PCR) performed o

218 difficile isolates from VRE swabs, and from C. difficile-positive stool samples, were genome sequenc

219 Infection with BI strains of C. difficile predicted poor outcomes in the MODIFY I/II

220 This signature suggested that C. difficile preferentially catabolizes branched chain a

221 C. difficile produces AI-2, a quorum sensing molecule th

222 Functional validation shows that the new C. difficile produces spores that are more resistant and

223 Here, we confirmed that ursodiol inhibits C. difficile R20291 spore germination and outgrowth, gro

224 and characterized Cwp22 (CDR20291_2601) from C. difficile R20291 to be involved in bacterial adhesion

225 e to restore colonization resistance against C. difficile remains unknown.

226 de 3, predominantly PCR ribotype (RT)023, of C. difficile revealed distinctive surface architecture c

227 We show that C. difficile reversibly differentiates into rough and sm

228 Modulated communities were inoculated with C. difficile (ribotype 027).

229 istent with trends across the United States, C. difficile RT106 was the second-most prevalent molecul

230 d N-acetylglucosamine utilizers that impedes C. difficile's access to these mucosal sugars and impair

231 C. difficile screening can be implemented within existin

232 pathology of CDI stems primarily from the 2 C. difficile-secreted exotoxins-toxin A (TcdA) and toxin

233 onization model, a CD0873-positive strain of C. difficile significantly outcompeted a CD0873-negative

234 rial virulence has been long recognized, and C. difficile sortase B (Cd-SrtB) has become an attractiv

235 Thus, we report the formation of an emerging C. difficile species, selected for metabolizing simple d

236 The C. difficile spore assembly pathway also exhibits notabl

237 understanding of the mechanisms controlling C. difficile spore formation and germination and describ

238 Assessment of C. difficile spore germination typically requires measur

239 As mice exposed to avirulent C. difficile spores ingested increasing quantities of la

240 The recalcitrance of C. difficile spores to currently available treatments an

241 C. difficile status was assessed by GDH EIA and real-tim

242 In contrast, 96% of C. difficile stool isolates were toxin-encoding.

243 observe that the host age and the infecting C. difficile strain influenced the severity of disease a

244 Using isogenic mutants of C. difficile strain NAPI/BI/027 deficient in TcdA (A-B+)

245 the transfer of 023_CTn3 to a non-toxigenic C. difficile strain, which may have implications for the

246 brary of 67 compounds against two pathogenic C. difficile strains (ATCC BAA 1870 and ATCC 43255), whi

247 ve implications for the use of non-toxigenic C. difficile strains as live attenuated vaccines.

248 as to assess bezlotoxumab's efficacy against C. difficile strains associated with increased rates of

249 y infection with TcdA- and/or TcdB-producing C. difficile strains but not with a TcdA(-)TcdB(-) isoge

250 One reason for this is that hypervirulent C. difficile strains often have a binary toxin termed th

251 tibiotic cefoperazone and then infected with C. difficile strains with varied disease-causing potenti

252 Indeed, against certain C. difficile strains, NCK-10 was more active than vancom

253 6 mug/ml), exhibited potent activity against C. difficile strains.

254 f binary toxin (CDT)-producing hypervirulent C. difficile strains.

255 were tested for non-toxigenic and toxigenic C. difficile (TCD).

256 performance characteristics of the Revogene C. difficile test (Meridian Bioscience, Cincinnati, OH,

257 Overall, the Revogene C. difficile test demonstrated a sensitivity of 85.0% (9

258 A case was defined as a positive C. difficile test in a person >=1 year old with no posit

259 presence of the tcdB gene using the Revogene C. difficile test, and results were compared with those

260 The Revogene C. difficile test, using clinical stool specimens for de

261 tomatic patients that had been submitted for C. difficile testing were enrolled at 7 sites throughout

262 udy was to assess the performance of various C. difficile tests and to compare clinical characteristi

263 , and outcomes of IBD patients with positive C. difficile tests.

264 on of the toxin B (tcdB) gene from toxigenic C. difficile The Revogene instrument is a new molecular

265 opmental processes to the infection cycle of C. difficile, the molecular mechanisms underlying how th

266 tential clinical lead for the development of C. difficile therapeutics but also highlights dramatic d

267 From Monoclonal Antibodies for C. difficile Therapy II, no participants (n = 0/69) with

268 data from MODIFY (Monoclonal Antibodies for C. difficile Therapy) I and II (NCT01241552 and NCT01513

269 imperative to the successful transmission of C. difficile this study was undertaken to investigate ph

270 ed acetate promotes host innate responses to C. difficile through coordinate action on neutrophils an

271 ota and how they may relate to recovery from C. difficile through FMT therapy.

272 One of the key factors which enables C. difficile to be a successful, highly transmissible pa

273 can potentially target the cell membrane of C. difficile to minimize relapse in the recovering patie

274 hese results define a mechanism exploited by C. difficile to repurpose toxic heme within the inflamed

275 The repeating unit of the C. difficile Toxin A (rARU, also known as CROPS [combine

276 e new peptides block the interaction between C. difficile toxin B (TcdB) and FZD receptors and pertur

277 The C. difficile toxin has an enzymatic component, termed CD

278 strains often have a binary toxin termed the C. difficile toxin, in addition to the enterotoxins TsdA

279 cluded all patients with a positive test for C. difficile (toxin or toxin genes) within the VHA Corpo

280 mated, and ultrasensitive assay that detects C. difficile toxins A and B in stool.

281 olecule counting technology for detection of C. difficile toxins A and B.

282 While it is clear that C. difficile toxins cause damaging colonic inflammation,

283 Ultrasensitive assays for detection of C. difficile toxins provide measurements of disease-spec

284 um sporogenes decreased the activity of both C. difficile toxins TcdA and TcdB.

285 xins: toxin A (TcdA), toxin B (TcdB) and the C. difficile transferase toxin (CDT)(2).

286 n as toxin A (TcdA), toxin B (TcdB), and the C. difficile transferase toxin (CDT).

287 Work in the last decade has revealed that C. difficile uses a distinct mechanism for sensing and t

288 rm a comprehensive DNA methylome analysis of C. difficile using 36 human isolates and observe a high

289 shows a strategy for improved production of C. difficile vaccine candidate in E. coli by using restr

290 der US adults of an investigational bivalent C. difficile vaccine that contains equal dosages of gene

291 The C. difficile vaccine was safe, well tolerated, and immun

292 Data on MRSA, C. difficile, vancomycin-resistant Enterococcus (VRE), a

293 rt tested positive for a pathogen other than C. difficile versus 49 patients (27%) in the post-GI PCR

294 rt tested positive for a pathogen other than C. difficile, vs. 49 patients (27%) in the post-GI PCR c

295 From 2559 randomized participants, C. difficile was isolated from 1588 (67.2%) baseline sto

296 The successful growth of C. difficile was most significantly correlated with the

297 1-2 d interrupted week-long periods in which C. difficile was undetectable.

298 ecal samples of patients tested positive for C. difficile were analyzed by assessing alpha and beta d

299 In summary, we identified rare C. difficile within-host genetic diversity in children,

300 odulation of distinct metabolic pathways for C. difficile WT, luxS and B. fragilis upon co-culture, i