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- Ciolfi, L., et al.
(författare)
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The Shannon Portal Installation: An Example of Interaction Design for Public Places
- 2007
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Ingår i: IEEE Computer Society. - : IEEE Communications Society. - 1051-4651. ; , s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- The portal dolmen project at Ireland's Shannon airport tackled the challenges of a public exhibition and revealed the importance of focusing on situated activities as well as the crucial need for incorporating physical and aesthetic concerns into the design.
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- Campbell, Christopher, et al.
(författare)
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Accumulation of succinyl coenzyme a perturbs the methicillin-resistant staphylococcus aureus (Mrsa) succinylome and is associated with increased susceptibility to beta-lactam antibiotics
- 2021
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Penicillin binding protein 2a (PBP2a)-dependent resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) is regulated by the activity of the tricarboxylic acid (TCA) cycle via a poorly understood mechanism. We report that mutations in sucC and sucD, but not other TCA cycle enzymes, negatively impact β-lactam resistance without changing PBP2a expression. Increased intracellular levels of succinyl coenzyme A (succinyl-CoA) in the sucC mutant significantly perturbed lysine succinylation in the MRSA proteome. Suppressor mutations in sucA or sucB, responsible for succinyl-CoA biosynthesis, reversed sucC mutant phenotypes. The major autolysin (Atl) was the most succinylated protein in the proteome, and increased Atl succinylation in the sucC mutant was associated with loss of autolytic activity. Although PBP2a and PBP2 were also among the most succinylated proteins in the MRSA proteome, peptidoglycan architecture and cross-linking were unchanged in the sucC mutant. These data reveal that perturbation of the MRSA succinylome impacts two interconnected cell wall phenotypes, leading to repression of autolytic activity and increased susceptibility to β-lactam antibiotics.
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- Ciolfi, L., et al.
(författare)
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The Shannon Portal Installation : Interaction Design for public spaces
- 2007
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Ingår i: IEEE Computer Society. - : IEEE Computer Society. - 1051-4651. ; 40:7, s. 64-71
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Tidskriftsartikel (refereegranskat)abstract
- The portal dolmen project at Ireland's Shannon airport tackled the challenges of a public exhibition and revealed the importance of focusing on situated activities as well as the crucial need for incorporating physical and aesthetic concerns into the design.
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- Gallagher, Laura A., et al.
(författare)
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Impaired Alanine Transport or Exposure to D-Cycloserine Increases the Susceptibility of MRSA to beta-lactam Antibiotics
- 2020
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Ingår i: Journal of Infectious Diseases. - : OXFORD UNIV PRESS INC. - 0022-1899 .- 1537-6613. ; 221:6, s. 1006-1016
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Tidskriftsartikel (refereegranskat)abstract
- Prolonging the clinical effectiveness of beta-lactams, which remain first-line antibiotics for many infections, is an important part of efforts to address antimicrobial resistance. We report here that inactivation of the predicted D-cycloserine (DCS) transporter gene cycA resensitized methicillin-resistant Staphylococcus aureus (MRSA) to beta-lactam antibiotics. The cycA mutation also resulted in hypersusceptibility to DCS, an alanine analogue antibiotic that inhibits alanine racemase and D-alanine ligase required for D-alanine incorporation into cell wall peptidoglycan. Alanine transport was impaired in the cycA mutant, and this correlated with increased susceptibility to oxacillin and DCS. The cycA mutation or exposure to DCS were both associated with the accumulation of muropeptides with tripeptide stems lacking the terminal D-ala-D-ala and reduced peptidoglycan cross-linking, prompting us to investigate synergism between beta-lactams and DCS. DCS resensitized MRSA to beta-lactams in vitro and significantly enhanced MRSA eradication by oxacillin in a mouse bacteremia model. These findings reveal alanine transport as a new therapeutic target to enhance the susceptibility of MRSA to beta-lactam antibiotics.
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- Kylander, Malin E., 1977-, et al.
(författare)
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Storm chasing : Tracking Holocene storminess in southern Sweden using mineral proxies from inland and coastal peat bogs
- 2023
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 299, s. 107854-
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Tidskriftsartikel (refereegranskat)abstract
- Severe extratropical winter storms are a recurrent feature of the European climate and cause widespread socioeconomic losses. Due to insufficient long-term data, it remains unclear whether storminess has shown a notable response to changes in external forcing over the past millennia, which impacts our ability to project future storminess in a changing climate. Reconstructing past storm variability is essential to improving our understanding of storms on these longer, missing timescales. Peat sequences from coastal ombrotrophic bogs are increasingly used for this purpose, where greater quantities of coarser grained beach sand are deposited by strong winds during storm events. Moving inland however, storm intensity decreases, as does sand availability, muting potential paleostorm signals in bogs. We circumvent these issues by taking the innovative approach of using mid-infrared (MIR) spectral data, supported by elemental information, from the inorganic fraction of Store Mosse Dune South (SMDS), a 5000-year-old sequence from a large peatland located in southern Sweden. We infer past changes in mineral composition and thereby, the grain size of the deposited material. The record is dominated by quartz, whose coarse nature was confirmed through analyses of potential local source sediments. This was supported by further mineralogical and elemental proxies of atmospheric input. Comparison of SMDS with within-bog and regionally relevant records showed that there is a difference in proxy and site response to what should be similar timing in shifts in storminess over the-100 km transect considered. We suggest the construction of regional storm stacks, built here by applying changepoint modelling to four transect sites jointly. This modelling approach has the effect of reinforcing signals in common while reducing the influence of random noise. The resulting Southern Sweden-Storm Stack dates stormier periods to 4495-4290, 3880-3790, 2885-2855, 2300-2005, 1175-1065 and 715-425 cal yr BP. By comparing with a newly constructed Western Scotland-Storm Stack and proximal dune records, we argue that regional storm stacks allow us to better compare past storminess over wider areas, gauge storm track movements and by extension, increase our understanding of the drivers of storminess on centennial to millennial timescales.
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- Zeden, Merve S., et al.
(författare)
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Metabolic reprogramming and altered cell envelope characteristics in a pentose phosphate pathway mutant increases MRSA resistance to β-lactam antibiotics
- 2023
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 19:7
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Tidskriftsartikel (refereegranskat)abstract
- Central metabolic pathways control virulence and antibiotic resistance, and constitute potential targets for antibacterial drugs. In Staphylococcus aureus the role of the pentose phosphate pathway (PPP) remains largely unexplored. Mutation of the 6-phosphogluconolactonase gene pgl, which encodes the only non-essential enzyme in the oxidative phase of the PPP, significantly increased MRSA resistance to β-lactam antibiotics, particularly in chemically defined media with physiologically-relevant concentrations of glucose, and reduced oxacillin (OX)-induced lysis. Expression of the methicillin-resistance penicillin binding protein 2a and peptidoglycan architecture were unaffected. Carbon tracing and metabolomics revealed extensive metabolic reprogramming in the pgl mutant including increased flux to glycolysis, the TCA cycle, and several cell envelope precursors, which was consistent with increased β-lactam resistance. Morphologically, pgl mutant cells were smaller than wild-type with a thicker cell wall and ruffled surface when grown in OX. The pgl mutation reduced resistance to Congo Red, sulfamethoxazole and oxidative stress, and increased resistance to targocil, fosfomycin and vancomycin. Levels of lipoteichoic acids (LTAs) were significantly reduced in pgl, which may limit cell lysis, while the surface charge of pgl cells was significantly more positive. A vraG mutation in pgl reversed the increased OX resistance phenotype, and partially restored wild-type surface charge, but not LTA levels. Mutations in vraF or graRS from the VraFG/GraRS complex that regulates DltABCD-mediated d-alanylation of teichoic acids (which in turn controls β-lactam resistance and surface charge), also restored wild-type OX susceptibility. Collectively these data show that reduced levels of LTAs and OX-induced lysis combined with a VraFG/GraRS-dependent increase in cell surface positive charge are accompanied by significantly increased OX resistance in an MRSA pgl mutant.
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