Explore the vast range of titles available.

Gram-negative bacteria are notoriously resistant to antibiotics, but the extent of the resistance varies broadly between species. We report that in significant human pathogens Acinetobacter baumannii , Pseudomonas aeruginosa , and Burkholderia spp., the differences in antibiotic resistance are largely defined by their penetration into the cell. For all tested antibiotics, the intracellular penetration was determined by a synergistic relationship between active efflux and the permeability barrier. We found that the outer membrane (OM) and efflux pumps select compounds on the basis of distinct properties and together universally protect bacteria from structurally diverse antibiotics. On the basis of their interactions with the permeability barriers, antibiotics can be divided into four clusters that occupy defined physicochemical spaces. Our results suggest that rules of intracellular penetration are intrinsic to these clusters. The identified specificities in the permeability barriers should help in the designing of successful therapeutic strategies against antibiotic-resistant pathogens. IMPORTANCE Multidrug-resistant strains of Gram-negative pathogens rapidly spread in clinics. Significant efforts worldwide are currently directed to finding the rules of permeation of antibiotics across two membrane envelopes of these bacteria. This study created the tools for analysis of and identified the major differences in antibacterial activities that distinguish the permeability barriers of P. aeruginosa , A. baumannii , Burkholderia thailandensis , and B. cepacia . We conclude that synergy between active efflux and the outer membrane barrier universally protects Gram-negative bacteria from antibiotics. We also found that the diversity of antibiotics affected by active efflux and outer membrane barriers is broader than previously thought and that antibiotics cluster according to specific biological determinants such as the requirement of specific porins in the OM, targeting of the OM, or specific recognition by efflux pumps. No universal rules of antibiotic permeation into Gram-negative bacteria apparently exist. Our results suggest that antibiotic clusters are defined by specific rules of permeation and that further studies could lead to their discovery. Multidrug-resistant strains of Gram-negative pathogens rapidly spread in clinics. Significant efforts worldwide are currently directed to finding the rules of permeation of antibiotics across two membrane envelopes of these bacteria. This study created the tools for analysis of and identified the major differences in antibacterial activities that distinguish the permeability barriers of P. aeruginosa , A. baumannii , Burkholderia thailandensis , and B. cepacia . We conclude that synergy between active efflux and the outer membrane barrier universally protects Gram-negative bacteria from antibiotics. We also found that the diversity of antibiotics affected by active efflux and outer membrane barriers is broader than previously thought and that antibiotics cluster according to specific biological determinants such as the requirement of specific porins in the OM, targeting of the OM, or specific recognition by efflux pumps. No universal rules of antibiotic permeation into Gram-negative bacteria apparently exist. Our results suggest that antibiotic clusters are defined by specific rules of permeation and that further studies could lead to their discovery.

Two membrane cell envelopes act as selective permeability barriers in Gram-negative bacteria, protecting cells against antibiotics and other small molecules. Significant efforts are being directed toward understanding how small molecules permeate these barriers. In this study, we developed an approach to analyze the permeation of compounds into Gram-negative bacteria and applied it to Pseudomonas aeruginosa , an important human pathogen notorious for resistance to multiple antibiotics. The approach uses mass spectrometric measurements of accumulation of a library of structurally diverse compounds in four isogenic strains of P. aeruginosa with varied permeability barriers. We further developed a machine learning algorithm that generates a deterministic classification model with minimal synonymity between the descriptors. This model predicted good permeators into P. aeruginosa with an accuracy of 89% and precision above 58%. The good permeators are broadly distributed in the property space and can be mapped to six distinct regions representing diverse chemical scaffolds. We posit that this approach can be used for more detailed mapping of the property space and for rational design of compounds with high Gram-negative permeability.

The impact of local climate conditions on air temperatures during a hot summer period over the United Kingdom in 2018 is studied using simple sensitivity experiments with a state‐of‐the‐art regional numerical weather prediction system. The experiments are designed to investigate the influence of sea surface temperature (SST) and soil moisture on the air temperatures over land. They involved applying changes to the analysed SST and soil moisture patterns with magnitudes consistent with the differences between forecast analysis and climatology. The results from daily 5‐day forecasts over an 11‐day period show that a 3°C reduction in SSTs reduces the simulated air temperatures averaged over all land points by just over 1°C. Moistening the soil while using the control SSTs reduces the temperatures by a little less than 1°C on average although this can be larger than 3°C locally. While the reduction in SST impacts the daily maximum and minimum temperatures to a similar extent, the increase in soil moisture had little impact on the daily minimum temperatures. Weather forecasting simulations are used to study the impact of local climate conditions on the 2018 UK heatwave. Focusing on an 11‐day period it is shown that changes in sea surface temperatures (SSTs) and soil moisture can change forecast temperatures by about 1°C. The impacts of soil moisture changes were more spatially variable than those of SSTs and predominantly influenced maximum temperatures.

Seedling establishment of Salicornia bigelovii was inhibited when seeds were sown in vermiculite watered with 0 ppt NaCl (control treatment) while the presence of 10 or 30 ppt NaCl had no inhibitory effect. During most of the experimental period the rate of water absorption in both cotyledons and embryo-axis of the salt treatments was at least twice that of the control. The organic material decreased in the cotyledons at the same time that it was increasing in the embryo-axis. Salinity did not show any apparent effect on reserve mobilization from the cotyledons to the embryo-axis. Ions accumulated with the increased salinity of the root environment in both the cotyledons and the embryo-axis. The former accumulated more than the latter except in the control treatment. After the 8th day from sowing the cotyledon ψ was —1⋅38, —1⋅95 and —2⋅74 MPa for the 0, 10 and 30 ppt treatments, respectively. The ψ gradients between external solution and the cotyledons were (0⋅80, 1⋅19 and 1⋅15 MPa for the 0, 10 and 30 ppt, respectively. The ψp of the control treatment was very low (0⋅02 MPa) when compared to the ones for the 10(0⋅53 MPa) and the 30 ppt (0⋅99 MPa) treatments. Glycinebetaine and soluble amino nitrogen accounted for over 90% of the organic component of the tissue osmolality with soluble sugars being responsible for the remainder. In the control the inorganic and organic components were of the same magnitude while in the 10 and 30 ppt treatments the inorganic was 8⋅6 and 14⋅1 fold greater than the organic component, respectively. Water movement into the control plants was apparently inhibited by the lack of inorganic solutes and as a consequence the cotyledons from these plants did not expand and seedling growth was severely reduced.