Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

Transport time scales in soil erosion modelling

Unlike sediment transport in rivers, erosion of agricultural soil must overcome its cohesive strength to move soil particles into suspension. Soil particle size variability also leads to fall velocities covering many orders of magnitude, and hence to different suspended travel distances in overland flow. Consequently, there is a large range of inherent time scales involved in transport of eroded soil. For conditions where there is a constant rainfall rate and detachment is the dominant erosion mechanism, we use the Hairsine-Rose (HR) model to analyze these timescales, to determine their magnitude (bounds) and to provide simple approximations for them. We show that each particle size produces both fast and slow timescales. The fast timescale controls the rapid adjustment away from experimental initial conditions – this happens so quickly that it cannot be measured in practice. The slow time scales control the subsequent transition to steady state and are so large that true steady state is rarely achieved in laboratory experiments. Both the fastest and slowest time scales are governed by the largest particle size class. Physically, these correspond to the rate of vertical movement between suspension and the soil bed, and the time to achieve steady state, respectively. For typical distributions of size classes, we also find that there is often a single dominant time scale that governs the growth in the total mass of sediment in the non-cohesive deposited layer. This finding allows a considerable simplification of the HR model leading to analytical expressions for the evolution of suspended and deposited layer concentrations

Solute and sediment transport at laboratory and field scale: Contributions of J.-Y. Parlange

We explore selected aspects of J.-Y. Parlange’s contributions to hydrological transport of solutes and sediments, including both the laboratory and field scales. At the laboratory scale, he provided numerous approximations for solute transport accounting for effects of boundary conditions, linear and nonlinear reactions, and means to determine relevant parameters. Theory was extended to the field scale with, on the one hand, the effect of varying surface boundary conditions and, on the other, effects of soil structure heterogeneity. Soil erosion modeling, focusing on the Hairsine-Rose model, was considered in several papers. His main results, which provide highly usable approximations for grain-size class dependent sediment transport and deposition, are described. The connection between solute in the soil and that in overland flow was also investigated by Parlange. His theory on exchange of solutes between these two compartments, and subsequent movement, is presented. Both deterministic and stochastic approaches were considered, with application to microbial transport. Beyond contaminant transport, Parlange’s fundamental contributions to the movement of solutes in hypersaline natural environments provided accurate predictions of vapor and liquid movement in desert, agricultural, and anthropogenic fresh-saline interfaces in porous media, providing the foundation for this area of research.This is the publisher’s final pdf. The article is copyrighted by the American Geophysical Union and can be found at: http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1944-7973.Keywords: modeling, surface water quality, infiltration, erosion, groundwater quality, soil moisture, vadose zone, sediment transport, groundwater transpor

Technical note: Image processing for continuous river turbidity monitoring – full-scale tests and potential applications

The development of continuous river turbidity monitoring systems is essential since this is a critical water quality metric linked to the presence of organic and inorganic suspended matter. Current monitoring practices are mainly limited by low spatial and temporal resolutions and costs. This results in the huge challenge of providing extensive and timely water quality monitoring at the global scale. In this work, we propose an image analysis procedure for river turbidity assessment using different camera systems (i.e. fixed-trap camera, camera on board an uncrewed aerial vehicle and a multispectral camera). We explored multiple types of camera installation setups during a river turbidity event artificially re-created on site. The outcomes prove that processed digital-camera data can properly represent the turbidity trends. Specifically, the experimental activities revealed that single-band values were the most reliable proxy for turbidity monitoring in the short term, more so than band ratios and indexes. The best camera positioning, orientation and lens sensitivity, as well as daily and seasonal changes in lightning and river flow conditions, may affect the accuracy of the results. The reliability of this application will be tested under different hydrological and environmental conditions during our next field experiments. The final goal of the work is the implementation of this camera system to support existing techniques and to help in finding innovative solutions to water resource monitoring.</p

Transport time scales in soil erosion modelling

Unlike sediment transport in rivers, erosion of agricultural soil must overcome its cohesive strength to move soil particles into suspension. Soil particle size variability also leads to fall velocities covering many orders of magnitude, and hence to different suspended travel distances in overland flow. Consequently, there is a large range of inherent time scales involved in transport of eroded soil. For conditions where there is a constant rainfall rate and detachment is the dominant erosion mechanism, we use the Hairsine-Rose (HR) model to analyze these timescales, to determine their magnitude (bounds) and to provide simple approximations for them. We show that each particle size produces both fast and slow timescales. The fast timescale controls the rapid adjustment away from experimental initial conditions – this happens so quickly that it cannot be measured in practice. The slow time scales control the subsequent transition to steady state and are so large that true steady state is rarely achieved in laboratory experiments. Both the fastest and slowest time scales are governed by the largest particle size class. Physically, these correspond to the rate of vertical movement between suspension and the soil bed, and the time to achieve steady state, respectively. For typical distributions of size classes, we also find that there is often a single dominant time scale that governs the growth in the total mass of sediment in the non-cohesive deposited layer. This finding allows a considerable simplification of the HR model leading to analytical expressions for the evolution of suspended and deposited layer concentrations

Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in Toxoplasma gondii

Expression of a bacterial transporter protein in Toxoplasma gondii results in parasite susceptibility to Formidomycin, a drug targeting isoprenoid precursor synthesis

Fosmidomycin Uptake into Plasmodium and Babesia-Infected Erythrocytes Is Facilitated by Parasite-Induced New Permeability Pathways

., a mouse malaria parasite. and related parasites. Our data provide further evidence that parasite-induced new permeability pathways may be exploited as routes for drug delivery