111 research outputs found
MrkH, a Novel c-di-GMP-Dependent Transcriptional Activator, Controls Klebsiella pneumoniae Biofilm Formation by Regulating Type 3 Fimbriae Expression
Klebsiella pneumoniae causes significant morbidity and mortality worldwide, particularly amongst hospitalized individuals. The principle mechanism for pathogenesis in hospital environments involves the formation of biofilms, primarily on implanted medical devices. In this study, we constructed a transposon mutant library in a clinical isolate, K. pneumoniae AJ218, to identify the genes and pathways implicated in biofilm formation. Three mutants severely defective in biofilm formation contained insertions within the mrkABCDF genes encoding the main structural subunit and assembly machinery for type 3 fimbriae. Two other mutants carried insertions within the yfiN and mrkJ genes, which encode GGDEF domain- and EAL domain-containing c-di-GMP turnover enzymes, respectively. The remaining two isolates contained insertions that inactivated the mrkH and mrkI genes, which encode for novel proteins with a c-di-GMP-binding PilZ domain and a LuxR-type transcriptional regulator, respectively. Biochemical and functional assays indicated that the effects of these factors on biofilm formation accompany concomitant changes in type 3 fimbriae expression. We mapped the transcriptional start site of mrkA, demonstrated that MrkH directly activates transcription of the mrkA promoter and showed that MrkH binds strongly to the mrkA regulatory region only in the presence of c-di-GMP. Furthermore, a point mutation in the putative c-di-GMP-binding domain of MrkH completely abolished its function as a transcriptional activator. In vivo analysis of the yfiN and mrkJ genes strongly indicated their c-di-GMP-specific function as diguanylate cyclase and phosphodiesterase, respectively. In addition, in vitro assays showed that purified MrkJ protein has strong c-di-GMP phosphodiesterase activity. These results demonstrate for the first time that c-di-GMP can function as an effector to stimulate the activity of a transcriptional activator, and explain how type 3 fimbriae expression is coordinated with other gene expression programs in K. pneumoniae to promote biofilm formation to implanted medical devices
Enhancement strategies for transdermal drug delivery systems: current trends and applications
Observation of B(s)0→J/ψpp¯ decays and precision measurements of the B(s)0 masses
The first observation of the decays
B
0
(
s
)
→
J
/
ψ
p
¯
p
is reported, using proton-proton collision data corresponding to an integrated luminosity of
5.2
fb
−
1
, collected with the LHCb detector. These decays are suppressed due to limited available phase space, as well as due to Okubo-Zweig-Iizuka or Cabibbo suppression. The measured branching fractions are
B
(
B
0
→
J
/
ψ
p
¯
p
)
=
[
4.51
±
0.40
(
stat
)
±
0.44
(
syst
)
]
×
10
−
7
,
B
(
B
0
s
→
J
/
ψ
p
¯
p
)
=
[
3.58
±
0.19
(
stat
)
±
0.39
(
syst
)
]
×
10
−
6
. For the
B
0
s
meson, the result is much higher than the expected value of
O
(
10
−
9
)
. The small available phase space in these decays also allows for the most precise single measurement of both the
B
0
mass as
5279.74
±
0.30
(
stat
)
±
0.10
(
syst
)
MeV
and the
B
0
s
mass as
5366.85
±
0.19
(
stat
)
±
0.13
(
syst
)
MeV
Observation of Two New Excited Ξb0 States Decaying to Λb0 K-π+
Two narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]<2.20(2.56) and Γ[Ξb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances
Observation of the decay Λ <sub>b</sub> <sup>0</sup> → ψ(2S)pπ<sup>−</sup>
International audienceThe Cabibbo-suppressed decay Λ → ψ(2S)pπ is observed for the first time using a data sample collected by the LHCb experiment in proton-proton collisions corresponding to 1.0, 2.0 and 1.9 fb of integrated luminosity at centre-of-mass energies of 7, 8 and 13 TeV, respectively. The ψ(2S) mesons are reconstructed in the μμ final state. The branching fraction with respect to that of the Λ → ψ(2S)pK decay mode is measured to b
Search for CP violation in Λb0→pK− and Λb0→pπ− decays
A search for CP violation in Λb0→pK− and Λb0→pπ− decays is presented using a sample of pp collisions collected with the LHCb detector and corresponding to an integrated luminosity of 3.0fb−1. The CP -violating asymmetries are measured to be ACPpK−=−0.020±0.013±0.019 and ACPpπ−=−0.035±0.017±0.020, and their difference ACPpK−−ACPpπ−=0.014±0.022±0.010, where the first uncertainties are statistical and the second systematic. These are the most precise measurements of such asymmetries to date
Evidence for an nc(1S)ff- resonance in B0 yc(1S)K+ decays
A Dalitz plot analysis of B0→ηc(1S)K+π- decays is performed using data samples of pp collisions collected with the LHCb detector at centre-of-mass energies of s=7,8 and 13TeV , corresponding to a total integrated luminosity of 4.7fb-1 . A satisfactory description of the data is obtained when including a contribution representing an exotic ηc(1S)π- resonant state. The significance of this exotic resonance is more than three standard deviations, while its mass and width are 4096±20-22+18MeV and 152±58-35+60MeV , respectively. The spin-parity assignments JP=0+ and JP=1- are both consistent with the data. In addition, the first measurement of the B0→ηc(1S)K+π- branching fraction is performed and gives B(B0→ηc(1S)K+π-)=(5.73±0.24±0.13±0.66)×10-4, where the first uncertainty is statistical, the second systematic, and the third is due to limited knowledge of external branching fractions
Amplitude analysis of the B0 (s)! K0K0 decays and measurement of the branching fraction of the B0! K0K0 decay
The and decays are studied using proton-proton collision data
corresponding to an integrated luminosity of 3fb. An untagged and
time-integrated amplitude analysis of
decays in two-body invariant mass regions of 150 MeV around the
mass is performed. A stronger longitudinal polarisation fraction in the decay, , is observed as compared to in the decay. The ratio of branching fractions of the two decays
is measured and used to determine .Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2019-004.html (LHCb
public pages
Search for Lepton-Universality Violation in B^{+}→K^{+}ℓ^{+}ℓ^{-} Decays.
A measurement of the ratio of branching fractions of the decays B^{+}→K^{+}μ^{+}μ^{-} and B^{+}→K^{+}e^{+}e^{-} is presented. The proton-proton collision data used correspond to an integrated luminosity of 5.0 fb^{-1} recorded with the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. For the dilepton mass-squared range 1.1<q^{2}<6.0 GeV^{2}/c^{4} the ratio of branching fractions is measured to be R_{K}=0.846_{-0.054}^{+0.060}_{-0.014}^{+0.016}, where the first uncertainty is statistical and the second systematic. This is the most precise measurement of R_{K} to date and is compatible with the standard model at the level of 2.5 standard deviations
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