92 research outputs found
PsrA controls the synthesis of the Pseudomonas aeruginosa quinolone signal via repression of the FadE homolog, PA0506
Pseudomonas aeruginosa is a ubiquitous, Gram-negative opportunistic pathogen that can cause disease in various sites within the human body. This bacterium is a major source of nosocomial infections that are often difficult to treat due to high intrinsic antibiotic resistance and coordinated virulence factor production. P. aeruginosa utilizes three cell-to-cell signal- ing systems to regulate numerous genes in response to cell density. One of these systems utilizes the small molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal [PQS]) as a signal that acts as a co-inducer for the transcriptional regulator PqsR. Quinolone signaling is required for virulence in multiple infection models, and PQS is produced during human infections, making this system an attractive target for potential drug development. In this study we have examined the role of a TetR-type transcriptional regulator, PsrA, in the regulation of PQS production by P. aeruginosa. Previous studies showed that PsrA regu- lates genes of the fatty acid β-oxidation pathway, including PA0506, which encodes a FadE homolog. In this report, we show that deletion of psrA resulted in a large decrease in PQS production and that co-deletion of PA0506 allowed PQS production to be restored to a wild type level. We also found that PQS production could be restored to the psrA mutant by the addition of oleic or octanoic acid. Taken together, our data suggest that psrA positively affects PQS production by repressing the transcription of PA0506, which leads to a decrease in the conversion of acyl-CoA compounds to enoyl-CoA compounds, thereby allowing some octanoyl-CoA to escape the ß-oxidation pathway and serve as a PQS precursor
The Transcriptional Regulator Np20 Is the Zinc Uptake Regulator in
Zinc is essential for all bacteria, but excess amounts of the metal can have toxic effects. To address this, bacteria have developed tightly regulated zinc uptake systems, such as the ZnuABC zinc transporter which is regulated by the Fur-like zinc uptake regulator (Zur). In Pseudomonas aeruginosa, a Zur protein has yet to be identified experimentally, however, sequence alignment revealed that the zinc-responsive transcriptional regulator Np20, encoded by np20 (PA5499), shares high sequence identity with Zur found in other bacteria. In this study, we set out to determine whether Np20 was functioning as Zur in P. aeruginosa. Using RT-PCR, we determined that np20 (hereafter known as zur) formed a polycistronic operon with znuC and znuB. Mutant strains, lacking the putative znuA, znuB, or znuC genes were found to grow poorly in zinc deplete conditions as compared to wild-type strain PAO1. Intracellular zinc concentrations in strain PAO-Zur (Δzur) were found to be higher than those for strain PAO1, further implicating the zur as the zinc uptake regulator. Reporter gene fusions and real time RT-PCR revealed that transcription of znuA was repressed in a zinc-dependent manner in strain PAO1, however zinc-dependent transcriptional repression was alleviated in strain PAO-Zur, suggesting that the P. aeruginosa Zur homolog (ZurPA) directly regulates expression of znuA. Electrophoretic mobility shift assays also revealed that recombinant ZurPA specifically binds to the promoter region of znuA and does not bind in the presence of the zinc chelator N,N′,N-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN). Taken together, these data support the notion that Np20 is the P. aeruginosa Zur, which regulates the transcription of the genes encoding the high affinity ZnuABC zinc transport system
Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa
Numerous species of bacteria use an elegant
regulatory mechanism known as quorum sensing to control
the expression of specific genes in a cell-density dependent
manner. In Gram-negative bacteria, quorum sensing systems
function through a cell-to-cell signal molecule (autoinducer)
that consists of a homoserine lactone with a fatty acid side
chain. Such is the case in the opportunistic human pathogen
Pseudomonas aeruginosa, which contains two quorum sensing
systems (las and rhl) that operate via the autoinducers,
N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-Lhomoserine
lactone. The study of these signal molecules has
shown that they bind to and activate transcriptional activator
proteins that specifically induce numerous P. aeruginosa
virulence genes. We report here that P. aeruginosa produces
another signal molecule, 2-heptyl-3-hydroxy-4-quinolone,
which has been designated as the Pseudomonas quinolone
signal. It was found that this unique cell-to-cell signal controlled
the expression of lasB, which encodes for the major
virulence factor, LasB elastase. We also show that the synthesis
and bioactivity of Pseudomonas quinolone signal were
mediated by the P. aeruginosa las and rhl quorum sensing
systems, respectively. The demonstration that 2-heptyl-3-
hydroxy-4-quinolone can function as an intercellular signal
sheds light on the role of secondary metabolites and shows
that P. aeruginosa cell-to-cell signaling is not restricted to
acyl-homoserine lactones. Originally published Proc. Natl. Acad. Sci, Vol. 96, No. 20, Sep. 199
Acinetobacter baumannii Regulates Its Stress Responses via the BfmRS Two-Component Regulatory System
Acinetobacter baumannii is a common nosocomial pathogen that utilizes numerous mechanisms to aid its survival in both the environment and the host. Coordination of such mechanisms requires an intricate regulatory network. We report here that A. baumannii can directly regulate several stress-related pathways via the two-component regulatory system BfmRS. Similar to previous studies, results from transcriptomic analysis showed that mutation of the BfmR response regulator causes dysregulation of genes required for the oxidative stress response, the osmotic stress response, the misfolded protein/heat shock response, Csu pilus/fimbria production, and capsular polysaccharide biosynthesis. We also found that the BfmRS system is involved in controlling siderophore biosynthesis and transport, and type IV pili production. We provide evidence that BfmR binds to various stress-related promoter regions and show that BfmR alone can directly activate transcription of some stress-related genes. Additionally, we show that the BfmS sensor kinase acts as a BfmR phosphatase to negatively regulate BfmR activity. This work highlights the importance of the BfmRS system in promoting survival of A. baumannii. IMPORTANCE Acinetobacter baumannii is a nosocomial pathogen that has extremely high rates of multidrug resistance. This organism’s ability to endure stressful conditions is a key part of its ability to spread in the hospital environment and cause infections. Unlike other members of the gammaproteobacteria, A. baumannii does not encode a homolog of the RpoS sigma factor to coordinate its stress response. Here, we demonstrate that the BfmRS two-component system directly controls the expression of multiple stress resistance genes. Our findings suggest that BfmRS is central to a unique scheme of general stress response regulation by A. baumannii
Search for lepton-flavor violation at HERA
A search for lepton-flavor-violating interactions and has been performed with the ZEUS detector using the entire HERA I
data sample, corresponding to an integrated luminosity of 130 pb^{-1}. The data
were taken at center-of-mass energies, , of 300 and 318 GeV. No
evidence of lepton-flavor violation was found, and constraints were derived on
leptoquarks (LQs) that could mediate such interactions. For LQ masses below
, limits were set on , where
is the coupling of the LQ to an electron and a
first-generation quark , and is the branching ratio of
the LQ to the final-state lepton ( or ) and a quark . For
LQ masses much larger than , limits were set on the four-fermion
interaction term for LQs that couple to an electron and a quark
and to a lepton and a quark , where and are
quark generation indices. Some of the limits are also applicable to
lepton-flavor-violating processes mediated by squarks in -Parity-violating
supersymmetric models. In some cases, especially when a higher-generation quark
is involved and for the process , the ZEUS limits are the most
stringent to date.Comment: 37 pages, 10 figures, Accepted by EPJC. References and 1 figure (Fig.
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The dependence of dijet production on photon virtuality in ep collisions at HERA
The dependence of dijet production on the virtuality of the exchanged photon,
Q^2, has been studied by measuring dijet cross sections in the range 0 < Q^2 <
2000 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of
38.6 pb^-1.
Dijet cross sections were measured for jets with transverse energy E_T^jet >
7.5 and 6.5 GeV and pseudorapidities in the photon-proton centre-of-mass frame
in the range -3 < eta^jet <0. The variable xg^obs, a measure of the photon
momentum entering the hard process, was used to enhance the sensitivity of the
measurement to the photon structure. The Q^2 dependence of the ratio of low- to
high-xg^obs events was measured.
Next-to-leading-order QCD predictions were found to generally underestimate
the low-xg^obs contribution relative to that at high xg^obs. Monte Carlo models
based on leading-logarithmic parton-showers, using a partonic structure for the
photon which falls smoothly with increasing Q^2, provide a qualitative
description of the data.Comment: 35 pages, 6 eps figures, submitted to Eur.Phys.J.
Multijet production in neutral current deep inelastic scattering at HERA and determination of alpha_s
Multijet production rates in neutral current deep inelastic scattering have
been measured in the range of exchanged boson virtualities 10 < Q2 < 5000 GeV2.
The data were taken at the ep collider HERA with centre-of-mass energy sqrt(s)
= 318 GeV using the ZEUS detector and correspond to an integrated luminosity of
82.2 pb-1. Jets were identified in the Breit frame using the k_T cluster
algorithm in the longitudinally invariant inclusive mode. Measurements of
differential dijet and trijet cross sections are presented as functions of jet
transverse energy E_{T,B}{jet}, pseudorapidity eta_{LAB}{jet} and Q2 with
E_{T,B}{jet} > 5 GeV and -1 < eta_{LAB}{jet} < 2.5. Next-to-leading-order QCD
calculations describe the data well. The value of the strong coupling constant
alpha_s(M_Z), determined from the ratio of the trijet to dijet cross sections,
is alpha_s(M_Z) = 0.1179 pm 0.0013(stat.) {+0.0028}_{-0.0046}(exp.)
{+0.0064}_{-0.0046}(th.)Comment: 22 pages, 5 figure
Search for a narrow charmed baryonic state decaying to D^*+/- p^-/+ in ep collisions at HERA
A resonance search has been made in the D^*+/- p^-/+ invariant-mass spectrum
with the ZEUS detector at HERA using an integrated luminosity of 126 pb^-1. The
decay channels D^*+ -> D^0 pi^+_s -> (K^- pi^+) pi^+_s and D^*+ -> D^0 pi^+_s
-> (K^- pi^+ pi^+ pi^-) pi^+_s (and the corresponding antiparticle decays) were
used to identify D^*+/- mesons. No resonance structure was observed in the
D^*+/- p^-/+ mass spectrum from more than 60000 reconstructed D^*+/- mesons.
The results are not compatible with a report of the H1 Collaboration of a
charmed pentaquark, Theta^0_c.Comment: 22 pages, 7 figures, 1 table; minor text revisions; 2 references
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