Bacterial biofilm formation is linked to several infections and foodborne disease outbreaks. To address this challenge, there is an unmet need to develop rechargeable antimicrobial materials that can provide continuous sanitation of contact surfaces, especially in the food industry. This study was aimed at evaluating a novel rechargeable antimicrobial polymer formed using poly(vinyl alcohol-co-ethylene) (PVA-co-PE) with halamine functionality to prevent biofilm formation with repeated exposure to high loads of bacteria and organic content and also to aid in inactivation of preformed biofilms upon contact with this novel material. The antibiofilm activity of this rechargeable antimicrobial material was evaluated using a combination of fluorescence and scanning electron microscopy techniques and biofilm metabolic activity analyses. The results determined on the basis of imaging and metabolic activity measurements demonstrated that halamine-functionalized polymer films significantly reduced Listeria innocua and Escherichia coli O157:H7 biofilm formation. This novel polymeric material maintained its antibiofilm activity with repeated cycles of extended exposure to high levels of bacterial load. These polymeric films were recharged using bleach and cleaned using mechanical sonication after each cycle of extended incubation with bacteria. Halamine-functionalized polymeric material also exhibited significant antibacterial activity against preformed biofilms on a model surface. In summary, our results demonstrate the potential of this antimicrobial material to provide continuous sanitation of surfaces and applications for inactivating preformed biofilms without extensive use of resources, including water and heat. This polymeric material may be used as a replacement for existing polymeric materials or as a coating on diverse materials.IMPORTANCE Conventional sanitizers can have limited efficacy in inactivating biofilms in areas with limited accessibility and buildup of organic biomass. Furthermore, none of the current approaches provide continuous sanitation of surfaces. There is a significant unmet need to develop and validate materials that can prevent biofilm formation as well as inactivate preformed biofilms. In this study, the efficacy of a copolymer film containing N-halamine against biofilms of L. innocua and E. coli O157:H7 was evaluated. The polymer film showed strong inhibitory activity against pregrown biofilm or prevented the growth of a new biofilm. The polymer film also maintained its antibiofilm activity after multiple cycles of exposure to high titers of bacterial load with recharging of the polymer film using bleach at intermediate steps between the cycles. Overall, the results demonstrate the potential of a novel antimicrobial material to inhibit and treat biofilms in food industry applications.

Enzyme-linked immunoassay (ELISA) is highly specific and selective towards target molecules and is convenient for on-site detection. However, in many cases, lack of high sensitivity makes it hard to reveal a significant colorimetric signal for detecting a trace amount of target molecules. Thus, analytical instruments are required for detection, which limits the application of ELISA for on-site detection. In the present study, a highly sensitive and naked-eyed detectable colorimetric biosensor for chloramphenicol (CAP) was prepared by incorporating ELISA onto surfaces of microporous and nanofibrous membranes. The high specific surface areas of the nanofibers significantly increased the number of antibodies covalently linked onto the fiber surfaces and binding capacity of the sensor with antigens present in a sample. With such an integration, the sensitivity of the ELISA sensor was dramatically increased, and a trace number of targets could reveal a naked-eye detectable color. The immunoassay sensor exhibited a significant naked-eye distinguishable color to chloramphenicol (CAP) at 0.3 ng/mL. The successful design and fabrication of the nanofibrous membrane immunoassay sensor provide new paths towards the development of on-site inspection sensors without the assistance from any instrument.

Emerging infectious diseases (EIDs) are a significant burden on global economies and public health. Most present personal protective equipment used to prevent EID transmission and infections is typically devoid of antimicrobial activity. We report on green bioprotective nanofibrous membranes (RNMs) with rechargeable antibacterial and antiviral activities that can effectively produce biocidal reactive oxygen species (ROS) solely driven by the daylight. The premise of the design is that the photoactive RNMs can store the biocidal activity under light irradiation and readily release ROS under dim light or dark conditions, making the biocidal function "always online." The resulting RNMs exhibit integrated properties of fast ROS production, ease of activity storing, long-term durability, robust breathability, interception of fine particles (>99%), and high bactericidal (>99.9999%) and virucidal (>99.999%) efficacy, which enabled to serve as a scalable biocidal layer for protective equipment by providing contact killing against pathogens either in aerosol or in liquid forms. The successful synthesis of these fascinating materials may provide new insights into the development of protection materials in a sustainable, self-recharging, and structurally adaptive form.

Porous nanofibrous membranes have ultrahigh specific surface areas and could be broadly employed in protein purification, enzyme immobilization, and biosensors with enhanced selectivity, sensitivity, and efficiency. However, large biomolecules, such as proteins, have hindered diffusion behavior in the micro-porous media, significantly reducing the benefits provided by the nanofibrous membranes. The study of protein diffusion in polyacrylonitrile (PAN) nanofibrous membranes produced under varied humidity and polymer concentration of electrospinning revealed that heterogeneous structures of the nanofibrous membranes possess much smaller effective pore sizes than the measured pore sizes, which significantly affects the diffusion of large molecules through the system though sizes of proteins and pH conditions also have great impacts. Only when the measured membrane pore size is at least 1000 times higher than the protein size, the diffusion behavior of the protein is predictable in the system. The results provide insights into the design and applications of proper nanofibrous materials for improved applications in protein purification and immobilizations.

Data-based detection and quantification of causation in complex, nonlinear dynamical systems is of paramount importance to science, engineering, and beyond. Inspired by the widely used methodology in recent years, the cross-map-based techniques, we develop a general framework to advance towards a comprehensive understanding of dynamical causal mechanisms, which is consistent with the natural interpretation of causality. In particular, instead of measuring the smoothness of the cross-map as conventionally implemented, we define causation through measuring the scaling law for the continuity of the investigated dynamical system directly. The uncovered scaling law enables accurate, reliable, and efficient detection of causation and assessment of its strength in general complex dynamical systems, outperforming those existing representative methods. The continuity scaling-based framework is rigorously established and demonstrated using datasets from model complex systems and the real world.

Enzyme-linked immunoassay (ELISA) is highly specific and selective towards target molecules and is convenient for on-site detection. However, in many cases, lack of high sensitivity makes it hard to reveal a significant colorimetric signal for detecting a trace amount of target molecules. Thus, analytical instruments are required for detection, which limits the application of ELISA for on-site detection. In the present study, a highly sensitive and naked-eyed detectable colorimetric biosensor for chloramphenicol (CAP) was prepared by incorporating ELISA onto surfaces of microporous and nanofibrous membranes. The high specific surface areas of the nanofibers significantly increased the number of antibodies covalently linked onto the fiber surfaces and binding capacity of the sensor with antigens present in a sample. With such an integration, the sensitivity of the ELISA sensor was dramatically increased, and a trace number of targets could reveal a naked-eye detectable color. The immunoassay sensor exhibited a significant naked-eye distinguishable color to chloramphenicol (CAP) at 0.3 ng/mL. The successful design and fabrication of the nanofibrous membrane immunoassay sensor provide new paths towards the development of on-site inspection sensors without the assistance from any instrument.

Background

Linezolid (LZD) is bactericidal against Mycobacterium tuberculosis, but it has treatment-limiting toxicities. A better understanding of exposure-response relationships governing LZD efficacy and toxicity will inform dosing strategies. Because in vitro monotherapy studies yielded conflicting results, we explored LZD pharmacokinetic/pharmacodynamic (PK/PD) relationships in vivo against actively and nonactively multiplying bacteria, including in combination with pretomanid.

Methods

Linezolid multidose pharmacokinetics were modeled in mice. Dose-fractionation studies were performed in acute (net bacterial growth) and chronic (no net growth) infection models. In acute models, LZD was administered alone or with bacteriostatic or bactericidal pretomanid doses. Correlations between PK/PD parameters and lung colony-forming units (CFUs) and complete blood counts were assessed.

Results

Overall, time above minimum inhibitory concentration (T>MIC) correlated best with CFU decline. However, in growth-constrained models (ie, chronic infection, coadministration with pretomanid 50 mg/kg per day), area under the concentration-time curve over MIC (AUC/MIC) had similar explanatory power. Red blood cell counts correlated strongly with LZD minimum concentration (Cmin).

Conclusions

Although T>MIC was the most consistent correlate of efficacy, AUC/MIC was equally predictive when bacterial multiplication was constrained by host immunity or pretomanid. In effective combination regimens, administering the same total LZD dose less frequently may be equally effective and cause less Cmin-dependent toxicity.