Differential development of antibiotic resistance and virulence between Acinetobacter species.

The two species that account for most cases of Acinetobacter-associated bacteremia in the United Kingdom are Acinetobacter lwoffii, often a commensal but also an emerging pathogen, and Acinetobacter baumannii, a well-known antibiotic-resistant species. While these species both cause similar types of human infection and occupy the same niche, A. lwoffii (unlike A. baumannii) has thus far remained susceptible to antibiotics. Comparatively little is known about the biology of A. lwoffii, and this is the largest study on it conducted to date, providing valuable insights into its behaviour and potential threat to human health. This study aimed to explain the antibiotic susceptibility, virulence, and fundamental biological differences between these two species. The relative susceptibility of A. lwoffii was explained as it encoded fewer antibiotic resistance and efflux pump genes than A. baumannii (9 and 30, respectively). While both species had markers of horizontal gene transfer, A. lwoffii encoded more DNA defense systems and harbored a far more restricted range of plasmids. Furthermore, A. lwoffii displayed a reduced ability to select for antibiotic resistance mutations, form biofilm, and infect both in vivo and in in vitro models of infection. This study suggests that the emerging pathogen A. lwoffii has remained susceptible to antibiotics because mechanisms exist to make it highly selective about the DNA it acquires, and we hypothesize that the fact that it only harbors a single RND system restricts the ability to select for resistance mutations. This provides valuable insights into how development of resistance can be constrained in Gram-negative bacteria. IMPORTANCE: Acinetobacter lwoffii is often a harmless commensal but is also an emerging pathogen and is the most common cause of Acinetobacter-derived bloodstream infections in England and Wales. In contrast to the well-studied and often highly drug-resistant A. baumannii, A. lwoffii has remained susceptible to antibiotics. This study explains why this organism has not evolved resistance to antibiotics. These new insights are important to understand why and how some species develop antibiotic resistance, while others do not, and could inform future novel treatment strategies.

Entanglements via Slip Springs with Soft, Coarse-Grained Models for Systems Having Explicit Liquid-Vapor Interfaces.

Recent advances in nano-rheology require that new techniques and models be developed to precisely describe the equilibrium and non-equilibrium characteristics of entangled polymeric materials and their interfaces at a molecular level. In this study, a slip-spring (SLSP) model is proposed to capture the dynamics of entangled polymers at interfaces, including those between liquids, liquids and vapors, and liquids and solids. The SLSP model employs a highly coarse-grained approach, which allows for comprehensive simulations of entire nano-rheological characterization systems using a particle-level description. The model relies on many-body dissipative particle dynamics (MDPD) non-bonded interactions, which permit explicit description of liquid-vapor interfaces; a compensating potential is introduced to ensure an unbiased representation of the shape of the liquid-vapor interface within the SLSP model. The usefulness of the proposed MDPD + SLSP approach is illustrated by simulating a capillary breakup rheometer (CaBR) experiment, in which a liquid droplet splits into two segments under the influence of capillary forces. We find that the predictions of the MDPD + SLSP model are consistent with experimental measurements and theoretical predictions. The proposed model is also verified by comparison to the results of explicit molecular dynamics simulations of an entangled polymer melt using a Kremer-Grest chain representation, both at equilibrium and far from equilibrium. Taken together, the model and methods presented in this study provide a reliable framework for molecular-level interpretation of high-polymer dynamics in the presence of interfaces.

Community Resource for Innovation in Polymer Technology (CRIPT): A Scalable Polymer Material Data Structure.

The Community Resource for Innovation in Polymer Technology (CRIPT) data model is designed to address the high complexity in defining a polymer structure and the intricacies involved with characterizing material properties.

Effect of Slip-Spring Parameters on the Dynamics and Rheology of Soft, Coarse-Grained Polymer Models.

Highly coarse-grained (hCG) linear polymer models allow for accessing long time and length scales by dissipative particle dynamics (DPD). This top-down strategy exploits the universal equilibrium behavior of long, flexible macromolecules by accounting only for the relevant interactions, such as molecular connectivity, and by parametrizing their strength via coarse-grained invariants, such as the mean-squared end-to-end distance. The description of the dynamics of long, entangled polymers, however, poses a challenge because (i) the noncrossability of the molecular backbones is not enforced by the soft interactions of an hCG model and (ii) the rheology involves multiple time and length scales, such as the Rouse-like dynamics on short scales and the reptation dynamics on long scales. One popular technique to effectively mimic the effect of entanglements in linear polymer melts via hCG models is slip-springs, and quantitative agreement with simulations that explicitly account for the noncrossability of molecular contours, experiments, and theoretical predictions has been achieved by identifying the time, length, and energy scales of the hCG model and adjusting the number of slip-springs per macromolecule. In the present work, we study how the spatial extent and the mobility of slip-springs affect the dynamics and discuss their implications in the choice of the degree of coarse-graining in computationally efficient hCG models.

Molecular simulations and hydrodynamic theory of nonlocal shear-stress correlations in supercooled fluids.

A supercooled fluid close to the glass transition develops nonlocal shear-stress correlations that anticipate the emergence of elasticity. We performed molecular dynamics simulations of a binary Lennard-Jones mixture at different temperatures and investigated the spatiotemporal autocorrelation function of the shear stress for different wavevectors, q, from a locally measured and Fourier-transformed stress tensor. Anisotropic correlations are observed at non-zero wavevectors, exhibiting strongly damped oscillations with a characteristic frequency ω(q). A comparison with a recently developed hydrodynamic theory [Maier et al., Phys. Rev. Lett. 119, 265701 (2017)] shows a remarkably good quantitative agreement between particle-based simulations and theoretical predictions.

Symmetric Diblock Copolymers in Cylindrical Confinement: A Way to Chiral Morphologies?

We investigate the confinement-induced formation and stability of helix morphologies in lamella-forming AB diblock copolymers via large-scale, particle-based, single-chain-in-mean-field simulations. Such helix structures are rarely observed in bulk or thin films. Structure formation is induced by quenching incompatibility, χN, from a disordered morphology. If the surfaces of the cylindrical confinement do not prefer one component over the other, we observe that stacked lamellae, with their normals along the cylinder axis, are the preferred morphology. Kinetically, this morphology initially forms close to the cylinder surface, whereas the spontaneous, spinodal microphase separation in the cylinder's interior gives rise to a microemulsion-like morphology, riddled with defects and no directional order. Subsequently, the ordered morphology on the cylinder surface progresses inward, pervading the entire volume. In case that the cylindrical pore is only partially filled, the additional confinement along the cylinder axis generally gives rise to incommensurability between the equilibrium spacing of stacked lamellae and the cylinder height. To accommodate this mismatch, the lamella normals will tilt away from the cylinder axis and generate helices of lamellae on the surface of the cylinder. Again, this order progresses from the cylinder surface inward, generating a chiral morphology. Because the spacing between the internal AB interfaces decreases upon approaching the helix center, the concomitant stress results in a decrease in the number of lamellae and the formation of unique dislocation defects. This type of chiral defect morphology is reproducibly formed by the kinetics of structure formation in partly filled cylindrical pores with nonpreferential surfaces and may find applications in photonic applications.

A multi-chain polymer slip-spring model with fluctuating number of entanglements: Density fluctuations, confinement, and phase separation.

Coarse grained simulation approaches provide powerful tools for the prediction of the equilibrium properties of polymeric systems. Recent efforts have sought to develop coarse-graining strategies capable of predicting the non-equilibrium behavior of entangled polymeric materials. Slip-link and slip-spring models, in particular, have been shown to be capable of reproducing several key aspects of the linear response and rheology of polymer melts. In this work, we extend a previously proposed multi-chain slip-spring model in a way that correctly incorporates the effects of the fluctuating environment in which polymer segments are immersed. The model is used to obtain the equation of state associated with the slip-springs, and the results are compared to those of related numerical approaches and an approximate analytical expression. The model is also used to examine a polymer melt confined into a thin film, where an inhomogeneous distribution of polymer segments is observed, and the corresponding inhomogeneities associated with density fluctuations are reflected on the spatial slip-spring distribution.