Conflicting interests in the pathogen-host tug of war : fungal micronutrient scavenging versus mammalian nutritional immunity

Funding: The authors are supported by the European Research Council (STRIFE project funded on grant number ERC-2009-AdG-249793, http://erc.europa.eu). AJPB is also supported by the Wellcome Trust (grant numbers 080088, 097377, www.wellcome.ac.uk) and the UK Biotechnology and Biological Sciences Research Council (grant number BB/F00513X/1, www.bbsrc.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1

Author Summary Dectin-1 is a pattern recognition receptor recognising the fungal cell-wall component, β-glucan, and plays an essential role in controlling C. albicans infections in both mouse and man. Candida albicans is part of the normal human microflora, yet is capable of causing superficial mucosal infections as well as life-threatening invasive diseases, particularly in patients whose immune function is compromised. Here we found that the contribution of Dectin-1 is limited to specific strains of C. albicans ; effects which are due to the differential adaptation of these pathogens during infection. Importantly, C. albicans strains showed variations in both the composition and nature of their cell walls, and it was these differences which influenced the role of Dectin-1. Crucially, we found that we could alter the fungal cell wall, and subsequent interactions with the host, using antifungal drugs. These findings have substantial implications for our understanding of the factors contributing to human susceptibility to infections with C. albicans , but also treatment strategies

Stress adaptation in a pathogenic fungus

Funding We are grateful to our funding bodies for their support. This work was supported by the European Commission [FINSysB, PITN-GA-2008-214004; STRIFE, ERC-2009-AdG-249793], by the UK Biotechnology and Biological Research Council [grant numbers BBS/B/06679; BB/C510391/1; BB/D009308/1; BB/F000111/1; BB/F010826/1; BB/F00513X/1], and by the Wellcome Trust [grant numbers 080088, 097377]. M.D.L. was also supported by a Carnegie/Caledonian Scholarship and a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust [grant number 096072]. Deposited in PMC for immediate release.Peer reviewedPublisher PD

Correction: Differential Adaptation of Candida albicans In Vivo Modulates Immune Recognition by Dectin-1

The b -glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found to play an essential role in controlling infections with Candida albicans , a normally commensal fungus in man which can cause superficial mucocutaneous infections as well as life-threatening invasive diseases. Here, using in vivo models of infection, we show that the requirement for Dectin-1 in the control of systemic Candida albicans infections is fungal strain-specific; a phenotype that only becomes apparent during infection and cannot be recapitulated in vitro . Transcript analysis revealed that this differential requirement for Dectin-1 is due to variable adaptation of C. albicans strains in vivo , and that this results in substantial differences in the composition and nature of their cell walls. In particular, we established that differences in the levels of cell-wall chitin influence the role of Dectin-1, and that these effects can be modulated by antifungal drug treatment. Our results therefore provide substantial new insights into the interaction between C. albicans and the immune system and have significant implications for our understanding of susceptibility and treatment of human infections with this pathogen

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

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Antibiotic resistance and plasmid-encoded resistance determinants

The increasing antibiotic resistance of bacterial pathogens is an alarming phenomenon of worldwide prevalence. The feasibility with which microorganisms obtain the resistance genes and express novel resistance mechanisms is becoming a serious problem in treatment of many infectious diseases. Selective pressure exerted by the abuse of antibiotics in and outside of human and veterinary medicine, their wide employment in animal husbandry and farming, is one of the main factors driving the dissemination and maintenance of resistance. This article briefly reviews the epidemiology of resistance as well as molecular mechanisms underlying the resistance. Significance of the phenomenon from the clinical point of view is considered. Types of mechanisms that have evolved for evasion of antimicrobial agent action are characterized. The spread of genetic determinants in the microbial community is described, with special emphasis on plasmid-encoded genes. The ways whereby plasmids capture the resistance genes, whether in the form of gene cassettes, integrons or transposons, and the modes of their transfer, as well as their importance from an epidemiological standpoint are presented. Lastly, this review focuses on various means of circumventing the antibiotic resistance problem

Purification and characterisation of ferritin from the Baltic blue mussel <i>Mytilus trossulus</i>

Baltic blue mussels <i>Mytilus trossulus</i> were collected from the Gulf of Gda&#X0144;sk (southern Baltic Sea) in order to isolate ferritin from its soft tissues, as well as to purify and characterise this protein.<br> &nbsp; &nbsp; Proteins were isolated from the inner organs of <i>M. trossulus</i> (hepatopancreas, gills and soft tissue residue) by thermal denaturation(70&deg;C) and acidification (pH 4.5) of the homogenates, followed by ammonium sulphate ((NH₄)₂SO₄) fractionation.The ferritin was then separated by ultracentrifugation (100 000 &times; g, 120 min.). The protein content in thepurified homogenates was determined by the Lowry method using bovine serum albumin(BSA) and horse spleen ferritin (HSF) as standards. PAGE-SDS and Western blotting analysis permitted identification of ferritinin the purified preparations. Additionally, the purified homogenates and mussel soft tissue were analysed for their heavy metal contents(especially cadmium and iron) in a Video 11 E atomic absorption spectrophotometer, following wet digestion of the samples (HNO₃/HClO₄).<br> &nbsp; &nbsp; The electrophoregrams showed that the inner organs of <i>M. trossulus</i> contained ferritin, which, like plant ferritin, is characterised by thepresence of subunits in the electrophoregram in the 26.6-28.0 kDa range. The highest ferritin content was recorded in the hepatopancreas,followed by the gills and the soft tissue residue. With regard to the sampling stations, the highest content of ferritin wasnoted in the animals sampled off Sopot (station D3), and in those collected by a diver off Jastarnia (W1) and Gdynia (W4). Ferritinisolated from the inner organs of mussels collected from these stations also contained the largest quantities of heavy metals(Cd and Fe). Ferritin isolated from the inner organs of mussels collected by a diver from wrecks - sites where the concentrationsof iron and other trace metals in the sea water are high - contained higher quantities of heavy metals (Cd and Fe) than the ferritinisolated from the inner organs of mussels collected with the drag. This confirms that ferritin is a protein able to store and transport not only iron, but also, though to a lesser extent, some otherheavy metals, including cadmium

Content and pattern of organic pollutants (PAHs, PCBs and DDT) in blue mussels Mytilus trossulus from the southern Baltic Sea

19 pages, 4 figures, 1 table.The objective of this work was to assess the contents and patterns of selected organic pollutants (polycyclic aromatic hydrocarbons - PAHs, polychlorinated biphenyls - PCBs, and chlorinated pesticides - DDT) in the southern part of the Baltic Sea proper, using blue mussels, Mytilus trossulus, as sentinel organisms. The mussels were collected from the Baltic Sea off Poland. The sampling programme focused on the mouths of the rivers Odra and Vistula, located respectively in the Pomeranian Bay and the Gulf of Gdansk, both known to be under anthropogenic pressure.This work was carried out within the framework of bilateral co-operation between the Institute of Oceanology, Sopot, Poland and the Institute of Chemical and Environmental Investigations (IIQAB/CID), Barcelona, Spain. It was also financially supported by the Institute of Oceanology statutory research project no. 2001/3.3.Peer reviewe

Identification of σE-Dependent Promoter Upstream of clpB from the Pathogenic Spirochaete Leptospira interrogans by Applying an E. coli Two-Plasmid System

There is limited information on gene expression in the pathogenic spirochaete Leptospira interrogans and genetic mechanisms controlling its virulence. Transcription is the first step in gene expression that is often determined by environmental effects, including infection-induced stresses. Alterations in the environment result in significant changes in the transcription of many genes, allowing effective adaptation of Leptospira to mammalian hosts. Thus, promoter and transcriptional start site identification are crucial for determining gene expression regulation and for the understanding of genetic regulatory mechanisms existing in Leptospira. Here, we characterized the promoter region of the L. interrogans clpB gene (clpBLi) encoding an AAA+ molecular chaperone ClpB essential for the survival of this spirochaete under thermal and oxidative stresses, and also during infection of the host. Primer extension analysis demonstrated that transcription of clpB in L. interrogans initiates at a cytidine located 41 bp upstream of the ATG initiation codon, and, to a lesser extent, at an adenine located 2 bp downstream of the identified site. Transcription of both transcripts was heat-inducible. Determination of clpBLi transcription start site, combined with promoter transcriptional activity assays using a modified two-plasmid system in E. coli, revealed that clpBLi transcription is controlled by the ECF &sigma;E factor. Of the ten L. interrogans ECF &sigma; factors, the factor encoded by LIC_12757 (LA0876) is most likely to be the key regulator of clpB gene expression in Leptospira cells, especially under thermal stress. Furthermore, clpB expression may be mediated by ppGpp in Leptospira