Effector ExoU from the type III secretion system is an important modulator of gene expression in lung epithelial cells in response to Pseudomonas aeruginosa infection

Pseudomonas aeruginosa is an important pathogen in immunocompromised patients and secretes a diverse set of virulence factors that aid colonization and influence host cell defenses. An important early step in the establishment of infection is the production of type III-secreted effectors translocated into host cells by the bacteria. We used cDNA microarrays to compare the transcriptomic response of lung epithelial cells to P. aeruginosa mutants defective in type IV pili, the type III secretion apparatus, or in the production of specific type III-secreted effectors. Of the 18,000 cDNA clones analyzed, 55 were induced or repressed after 4 It of infection and could be classified into four different expression patterns. These include (i) host genes that are induced or repressed in a type III secretion-independent manner (32 clones), (ii) host genes induced specifically by ExoU (20 clones), and (iii) host genes induced in an ExoU-independent but type III secretion dependent manner (3 clones). In particular, ExoU was essential for the expression of immediate-early response genes, including the transcription factor c-Fos. ExoU-dependent gene expression was mediated in part by early and transient activation of the AN transcription factor complex. In conclusion, the present study provides a detailed insight into the response of epithelial cells to infection and indicates the significant role played by the type III virulence mechanism in the initial host response.

Simulating quantum interference in a three-level system with perpendicular transition dipole moments

We consider a three-level V-type atomic system with the ground state coupled by a laser field to only one of the excited states, and with the two excited states coupled together by a dc field. Although the dipole moments of the two dipole-allowed transitions are assumed perpendicular, we demonstrate that this system emulates to a large degree a three-level system with parallel dipole moments-the latter being a system that exhibits quantum interference and displays a number of interesting features. As examples, we show that the system can produce extremely large values for the intensity-intensity correlation function, and that its resonance fluorescence spectrum can display ultranarrow lines. The dressed states for this system are identified, and the spectral features are interpreted in terms of transitions among these dressed states. We also show that this system is capable of exhibiting considerable squeezing.

An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination

Several pathogenic strains of Escherichia coli exploit type III secretion to inject effector proteins into human cells, which then subvert eukaryotic cell biology to the bacterium's advantage. We have exploited bioinformatics and experimental approaches to establish that the effector repertoire in the Sakai strain of enterohemorrhagic E. coli (EHEC) O157:H7 is much larger than previously thought. Homology searches led to the identification of > 60 putative effector genes. Thirteen of these were judged to be likely pseudogenes, whereas 49 were judged to be potentially functional. In total, 39 proteins were confirmed experimentally as effectors: 31 through proteomics and 28 through translocation assays. At the protein level, the EHEC effector sequences fall into > 20 families. The largest family, the NleG family, contains 14 members in the Sakai strain alone. EHEC also harbors functional homologs of effectors from plant pathogens (HopPtoH, HopW, AvrA) and from Shigella (OspD, OspE, OspG), and two additional members of the Map/IpgB family. Genes encoding proven or predicted effectors occur in > 20 exchangeable effector loci scattered throughout the chromosome. Crucially, the majority of functional effector genes are encoded by nine exchangeable effector loci that lie within lambdoid prophages. Thus, type III secretion in E. coli is linked to a vast phage metagenome, acting as a crucible for the evolution of pathogenicity.

Type III secretion contact-dependent model for the intracellular development of Chlamydia

The medically significant genus Chlamydia is a class of obligate intracellular bacterial pathogens that replicate within vacuoles in host eukaryotic cells termed inclusions. Chlamydia's developmental cycle involves two forms; an infectious extracellular form, known as an elementary body (EB), and a non-infectious form, known as the reticulate body (RB), that replicates inside the vacuoles of the host cells. The RB surface is covered in projections that are in intimate contact with the inclusion membrane. Late in the developmental cycle, these reticulate bodies differentiate into the elementary body form. In this paper, we present a hypothesis for the modulation of these developmental events involving the contact-dependent type III secretion (TTS) system. TTS surface projections mediate intimate contact between the RB and the inclusion membrane. Below a certain number of projections, detachment of the RB provides a signal for late differentiation of RB into EB. We use data and develop a mathematical model investigating this hypothesis. If the hypothesis proves to be accurate, then we have shown that increasing the number of inclusions per host cell will increase the number of infectious progeny EB until some optimal number of inclusions. For more inclusions than this optimum, the infectious yield is reduced because of spatial restrictions. We also predict that a reduction in the number of projections on the surface of the RB (and as early as possible during development) will significantly reduce the burst size of infectious EB particles. Many of the results predicted by the model can be tested experimentally and may lead to the identification of potential targets for drug design. © Society for Mathematical Biology 2006.

Wolbachia pipientis: intracellular infection and pathogenesis in Drosophila

Wolbachia pipientis is a vertically transmitted, obligate intracellular symbiont of arthropods. The bacterium is best known for its ability to manipulate host reproductive biology where it can induce cytoplasmic incompatibility, parthenogenesis, feminization and male-killing. In addition to the various reproductive phenotypes it generates through interaction with host reproductive tissue it is also known to infect somatic tissues. However, relatively little is known about the consequences of infection of these tissues with the exception that in some hosts Wolbachia acts as a classical mutualist and in others a pathogen, dramatically shortening adult insect lifespan. Manipulation experiments have demonstrated that the severity of Wolbachia-induced effects on the host is determined by a combination of host genotype, Wolbachia strain, host tissue localization, and interaction with the environment. The recent completion of the whole genome sequence of Wolbachia pipientis wMel strain indicates that it is likely to use a type IV secretion system to establish and maintain infection in its host. Moreover, an unusual abundance of genes encoding proteins with eukaryotic-like ankyrin repeat domains suggest a function in the various described phenotypic effects in hosts.

Pseudomonas aeruginosa fimL regulates multiple virulence functions by intersecting with Vfr-modulated pathways

Virulence of Pseudomonas aeruginosa involves the co-ordinate expression of a range of factors including type IV pili (tfp), the type III secretion system (TTSS) and quorum sensing. Tfp are required for twitching motility, efficient biofilm formation, and for adhesion and type III secretion (TTS)-mediated damage to mammalian cells. We describe a novel gene (fimL) that is required for tfp biogenesis and function, for TTS and for normal biofilm development in P. aeruginosa. The predicted product of fimL is homologous to the N-terminal domain of ChpA, except that its putative histidine and threonine phosphotransfer sites have been replaced with glutamine. fimL mutants resemble vfr mutants in many aspects including increased autolysis, reduced levels of surface-assembled tfp and diminished production of type III secreted effectors. Expression of vfr in trans can complement fimL mutants. vfr transcription and production is reduced in fimL mutants whereas cAMP levels are unaffected. Deletion and insertion mutants of fimL frequently revert to wild-type phenotypes suggesting that an extragenic suppressor mutation is able to overcome the loss of fimL. vfr transcription and production, as well as cAMP levels, are elevated in these revertants, while Pseudomonas quinolone signal (PQS) production is reduced. These results suggest that the site(s) of spontaneous mutation is in a gene(s) which lies upstream of vfr transcription, cAMP, production, and PQS synthesis. Our studies indicate that Vfr and FimL are components of intersecting pathways that control twitching motility, TTSS and autolysis in P. aeruginosa.

Effect of quantum interference on a three-level atom driven by two laser fields

We study the effect of quantum interference on the population distribution and absorptive properties of a V-type three-level atom driven by two lasers of unequal intensities and different angular frequencies. Three coupling configurations of the lasers to the atom are analysed: (a) both lasers coupled to the same atomic transition, (b) each laser coupled to different atomic transition and (c) each laser coupled to both atomic transitions. Dressed stales for the three coupling configurations are identified, and the population distribution and absorptive properties of the weaker field are interpreted in terms of transition dipole moments and transition frequencies among these dressed states. In particular, we find that in the first two cases there is no population inversion between the bare atomic states, but the population can be trapped in a superposition of the dressed states induced by quantum interference and the stronger held. We show that the trapping of the population, which results from the cancellation of transition dipole moments, does not prevent the weaker field to be coupled to the cancelled (dark) transitions. As a result, the weaker field can be strongly amplified on transparent transitions. In the case of each laser coupled to both atomic transitions the population can be trapped in a linear superposition of the excited bare atomic states leaving the ground state unpopulated in the steady state. Moreover, we find that the absorption rate of the weaker field depends on the detuning of the strong field from the atomic resonances and the splitting between the atomic excited states. When the strong held is resonant to one of the atomic transitions a quasi-trapping effect appears in one of the dressed states. In the quasi-trapping situation all the transition dipole moments are different from zero, which allows the weaker field to be amplified on the inverted transitions. When the strong field is tuned halfway between the atomic excited states, the population is completely trapped in one of the dressed states and no amplification is found for the weaker field.

Decoherence and coherent population transfer between two coupled systems

We show that an arbitrary system described by two dipole moments exhibits coherent superpositions of internal states that can be completely decoupled fi om the dissipative interactions (responsible for decoherence) and an external driving laser field. These superpositions, known as dark or trapping states, can he completely stable or can coherently interact with the remaining states. We examine the master equation describing the dissipative evolution of the system and identify conditions for population trapping and also classify processes that can transfer the population to these undriven and nondecaying states. It is shown that coherent transfers are possible only if the two systems are nonidentical, that is the transitions have different frequencies and/or decay rates. in particular, we find that the trapping conditions can involve both coherent and dissipative interactions, and depending on the energy level structure of the system, the population can be trapped in a linear superposition of two or more bare states, a dressed state corresponding to an eigenstate of the system plus external fields or, in some cases. in one of the excited states of the system. A comprehensive analysis is presented of the different processes that are responsible for population trapping, and we illustrate these ideas with three examples of two coupled systems: single V- and Lambda-type three-level atoms and two nonidentical tao-level atoms, which are known to exhibit dark states. We show that the effect of population trapping does not necessarily require decoupling of the antisymmetric superposition from the dissipative interactions. We also find that the vacuum-induced coherent coupling between the systems could be easily observed in Lambda-type atoms. Our analysis of the population trapping in two nonidentical atoms shows that the atoms can be driven into a maximally entangled state which is completely decoupled from the dissipative interaction.

Ultra-compact dwarf galaxies: a new class of compact stellar system discovered in the Fornax Cluster

We have used the 2dF spectrograph on the Anglo-Australian Telescope to obtain a complete spectroscopic sample of all objects in the magnitude range, 16.5 < bj < 19.8, regardless of morphology, in an area centred on the Fornax Cluster of galaxies. Among the unresolved targets are five objects which are members of the Fornax Cluster. They are extremely compact stellar systems with scale lengths less than 40 parsecs. These ultra-compact dwarfs are unlike any known type of stellar system, being more compact and significantly less luminous than other compact dwarf galaxies, yet much brighter than any globular cluster.

Greenberger-Horne-Zeilinger-type and W-type entangled coherent states: Generation and Bell-type inequality tests without photon counting

We study Greenberger-Horne-Zeilinger-type (GHZ-type) and W-type three-mode entangled coherent states. Both types of entangled coherent states violate Mermin's version of the Bell inequality with threshold photon detection (i.e., without photon counting). Such an experiment can be performed using linear optics elements and threshold detectors with significant Bell violations for GHZ-type entangled coherent states. However, to demonstrate Bell-type inequality violations for W-type entangled coherent states, additional nonlinear interactions are needed. We also propose an optical scheme to generate W-type entangled coherent states in free-traveling optical fields. The required resources for the generation are a single-photon source, a coherent state source, beam splitters, phase shifters, photodetectors, and Kerr nonlinearities. Our scheme does not necessarily require strong Kerr nonlinear interactions; i.e., weak nonlinearities can be used for the generation of the W-type entangled coherent states. Furthermore, it is also robust against inefficiencies of the single-photon source and the photon detectors.

Ultracompact dwarf galaxies in the Fornax Cluster

By utilizing the large multiplexing advantage of the Two-degree Field spectrograph on the Anglo-Australian Telescope, we have been able to obtain a complete spectroscopic sample of all objects in a predefined magnitude range, 16.5 < b(j) < 19.7 regardless of morphology, in an area toward the center of the Fornax Cluster of galaxies. Among the unresolved or marginally resolved targets, we have found five objects that are actually at the redshift of the Fornax Cluster; i.e., they are extremely compact dwarf galaxies or extremely large star clusters. All five have absorption-line spectra. With intrinsic sizes of less than 1.1 HWHM (corresponding to approximately 100 pc at the distance of the cluster), they are more compact and significantly less luminous than other known compact dwarf galaxies, yet much brighter than any globular cluster. In this paper we present new ground-based optical observations of these enigmatic objects. In addition to having extremely high central surface brightnesses, these objects show no evidence of any surrounding low surface brightness envelopes down to much fainter limits than is the case for, e.g., nucleated dwarf elliptical galaxies. Thus, if they are not merely the stripped remains of some other type of galaxy, then they appear to have properties unlike any previously known type of stellar system.

Zero-non-zero patterned vector error correction modeling for I(2) cointegrated time series with applications in testing PPP and stock market relationships

Vector error-correction models (VECMs) have become increasingly important in their application to financial markets. Standard full-order VECM models assume non-zero entries in all their coefficient matrices. However, applications of VECM models to financial market data have revealed that zero entries are often a necessary part of efficient modelling. In such cases, the use of full-order VECM models may lead to incorrect inferences. Specifically, if indirect causality or Granger non-causality exists among the variables, the use of over-parameterised full-order VECM models may weaken the power of statistical inference. In this paper, it is argued that the zero–non-zero (ZNZ) patterned VECM is a more straightforward and effective means of testing for both indirect causality and Granger non-causality. For a ZNZ patterned VECM framework for time series of integrated order two, we provide a new algorithm to select cointegrating and loading vectors that can contain zero entries. Two case studies are used to demonstrate the usefulness of the algorithm in tests of purchasing power parity and a three-variable system involving the stock market.