Iron Acquisition Mechanisms and Their Role in the Virulence of Burkholderia Species

Burkholderia is a genus within the β-Proteobacteriaceae that contains at least 90 validly named species which can be found in a diverse range of environments. A number of pathogenic species occur within the genus. These include Burkholderia cenocepacia and Burkholderia multivorans, opportunistic pathogens that can infect the lungs of patients with cystic fibrosis, and are members of the Burkholderia cepacia complex (Bcc). Burkholderia pseudomallei is also an opportunistic pathogen, but in contrast to Bcc species it causes the tropical human disease melioidosis, while its close relative Burkholderia mallei is the causative agent of glanders in horses. For these pathogens to survive within a host and cause disease they must be able to acquire iron. This chemical element is essential for nearly all living organisms due to its important role in many enzymes and metabolic processes. In the mammalian host, the amount of accessible free iron is negligible due to the low solubility of the metal ion in its higher oxidation state and the tight binding of this element by host proteins such as ferritin and lactoferrin. As with other pathogenic bacteria, Burkholderia species have evolved an array of iron acquisition mechanisms with which to capture iron from the host environment. These mechanisms include the production and utilization of siderophores and the possession of a haem uptake system. Here, we summarize the known mechanisms of iron acquisition in pathogenic Burkholderia species and discuss the evidence for their importance in the context of virulence and the establishment of infection in the host. We have also carried out an extensive bioinformatic analysis to identify which siderophores are produced by each Burkholderia species that is pathogenic to humans

The LIM and SH3 domain protein family: structural proteins or signal transducers or both?

LIM and SH3 Protein 1 (LASP-1) was initially identified from a cDNA library of metastatic axillary lymph nodes (MLN) more than a decade ago. It was found to be overexpressed in human breast and ovarian cancer and became the first member of a newly defined LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. LASP2, a novel LASP1-related gene was first identified and characterized in silico. Subsequently it proved to be a splice variant of the Nebulin gene and therefore was also termed LIM/nebulette. LASP-1 and -2 are highly conserved in their LIM, nebulin-like and SH3 domains but differ significantly at their linker regions. Both proteins are ubiquitously expressed and involved in cytoskeletal architecture, especially in the organization of focal adhesions. Here we present the first systematic review to summarize all relevant data concerning their domain organization, expression profiles, regulating factors and function. We compile evidence that both, LASP-1 and LASP-2, are important during early embryo- and fetogenesis and are highly expressed in the central nervous system of the adult. However, only LASP-1 seems to participate significantly in neuronal differentiation and plays an important functional role in migration and proliferation of certain cancer cells while the role of LASP-2 is more structural. The increased expression of LASP-1 in breast tumours correlates with high rates of nodal-metastasis and refers to a possible relevance as a prognostic marker

Supernova remnants and gamma-ray sources

A review of the possible relationship between gamma-ray sources and supernova remnants (SNRs) is presented. Particular emphasis is given to the analysis of the observational status of the problem of cosmic ray acceleration at SNR shock fronts. All positional coincidences between SNRs and unidentified gamma-ray sources listed in the Third EGRET Catalog at low Galactic latitudes are discussed on a case by case basis. For several coincidences of particular interest, new CO(J=1-0) and radio continuum maps are shown, and the mass content of the SNR surroundings is determined. The contribution to the gamma-ray flux observed that might come from cosmic ray particles (particularly nuclei) locally accelerated at the SNR shock fronts is evaluated. We discuss the prospects for future research in this field and remark on the possibilities for observations with forthcoming gamma-ray instruments.Comment: Final version of a review article, to appear in the Physics Reports (82 pages, 31 figures). Figures requiring high quality are just too large and too many to be included here. Please download them from http://www.angelfire.com/id/dtorres/down3.htm

Reducing GHGs from UK households ‐ an examination of local authority‐level data

As the threat of irreversible climate change has increased over time, the UK has focused on reducing its carbon emission levels. International treaties such as the Kyoto Protocol have informed national targets, directing the UK in reducing its climate impact. In order to achieve this an understanding of the factors that affect carbon emission reductions is vital. Identifying what dictates the success of UK local authorities in reducing their carbon emissions addresses this problem. The research uses secondary data regarding local authorities’ carbon emissions and regression analyses to explore the key factors affecting domestic emission levels over time. The research goes into further detail than existing literature through exploring sources of emissions across different sectors and analysing emissions reductions specifically between 2005‐2016. Substantial and relatively consistent domestic emissions reductions were achieved in this time frame, exceeding the reductions provided by decarbonisation of the electricity grid. Standard deviations of 3% were observed in this sector, compared with 12% from Industrial & Commercial emissions. While population density demonstrated a statistically significant correlation with domestic GHG reductions, gross disposable household income was not found to be significant; however, it is a relevant indicator of total emissions levels in 2016. Through identifying these factors, suggestions to local government are made such as the implementation of region‐specific strategies, tailoring these to the exact characteristics of a local authority. Furthermore, consideration of population density in conjunction with domestic and urban planning will allow for future emissions reductions to occur across the UK

Did Egret Detect Distant Supernova Remnants?

It might be thought that supernova remnants (SNRs) more distant than a few kiloparsec from Earth could not have been detected by the EGRET experiment. This work analyzes the observational status of this statement in the light of new CO studies of SNRs.Comment: Accepted for publication in Advances in Space Research, in High Energy Studies of Supernova Remnants and Neutron Stars, eds. W. Becker and W. Hermsen (2003

Supernova-Remnant Origin of Cosmic Rays?

It is thought that Galactic cosmic ray (CR) nuclei are gradually accelerated to high energies (up to ~300 TeV/nucleon, where 1TeV=10^12eV) in the expanding shock-waves connected with the remnants of powerful supernova explosions. However, this conjecture has eluded direct observational confirmation^1,2 since it was first proposed in 1953 (ref. 3). Enomoto et al.^4 claim to have finally found definitive evidence that corroborates this model, proposing that the very-high-energy, TeV-range, gamma-rays from the supernova remnant (SNR) RX J1713.7-3946 are due to the interactions of energetic nuclei in this region. Here we argue that their claim is not supported by the existing multiwavelength spectrum of this source. The search for the origin(s) of Galactic cosmic ray nuclei may be closing in on the long-suspected supernova-remnant sources, but it is not yet over.Comment: 4 pages, 1 Figur

Mechanisms of Bacterial Extracellular Electron Exchange.

The biochemical mechanisms by which microbes interact with extracellular soluble metal ions and insoluble redox-active minerals have been the focus of intense research over the last three decades. The process presents two challenges to the microorganism; firstly electrons have to be transported at the cell surface, which in Gram negative bacteria presents an additional problem of electron transfer across the ~ 6 nm of the outer membrane. Secondly the electrons must be transferred to or from the terminal electron acceptors or donors. This review covers the known mechanisms that bacteria use to transport electrons across the cell envelope to external electron donors/acceptors. In Gram negative bacteria electron transfer across the outer membrane involves the use of an outer membrane β-barrel and cytochrome. These can be in the form of a porin-cytochrome protein, such as Cyc2 of Acidothiobacillus ferrioxydans, or a multiprotein porin-cytochrome complex like MtrCAB of Shewanella oneidensis MR-1. For mineral respiring organisms there is the additional challenge of transferring the electrons from the cell to mineral surface. For the strict anaerobe Geobacter sulfurreducens this requires electron transfer through conductive pili to associated cytochrome OmcS that directly reduces Fe(III)oxides, while the facultative anaerobe S. oneidensis MR-1 accomplishes mineral reduction through direct membrane contact, contact through filamentous extentions and soluble flavin shuttles, all of which require the outer membrane cytochromes MtrC and OmcA in addition to secreted flavin

The Crystal Structure of the Extracellular 11-heme Cytochrome UndA Reveals a Conserved 10-heme Motif and Defined Binding Site for Soluble Iron Chelates

Members of the genus Shewanella translocate deca- or undeca-heme cytochromes to the external cell surface thus enabling respiration using extracellular minerals and polynuclear Fe(III) chelates. The high resolution structure of the first undeca-heme outer membrane cytochrome, UndA, reveals a crossed heme chain with four potential electron ingress/egress sites arranged within four domains. Sequence and structural alignment of UndA and the deca-heme MtrF reveals the extra heme of UndA is inserted between MtrF hemes 6 and 7. The remaining UndA hemes can be superposed over the heme chain of the decaheme MtrF, suggesting that a ten heme core is conserved between outer membrane cytochromes. The UndA structure has also been crystallographically resolved in complex with substrates, an Fe(III)-nitrilotriacetate dimer or an Fe(III)-citrate trimer. The structural resolution of these UndA-Fe(III)-chelate complexes provides a rationale for previous kinetic measurements on UndA and other outer membrane cytochromes