Disinfection of Pseudomonas aeruginosa from N95 respirators with ozone: a pilot study.

INTRODUCTION: Personal protective equipment shortages require the reuse of N95 respirators. We sought the necessary conditions for ozone to disinfect N95 respirators for reuse and the effects of multiple cycles of exposure. METHODS: Portions of 3M 1870 N95 respirators were exposed to ozone at 400 ppm with 80% humidity for 2 hours to determine effectiveness of ozone on killing Pseudomonas aeruginosa. Entire 3M 1870 N95 respirators were exposed to five cycles of 400 ppm with 80% or higher humidity for 2 hours then evaluated for ozone's effects on airflow resistance, filtration efficiency, strap strength and quantitative fit. RESULTS: Ozone exposure disinfected 3M 1870 N95 respirators heavily inoculated with P. aeruginosa. Ozone exposure did not negatively affect the airflow resistance, filtration efficiency, strap strength or fit of the 3M 1870 N95 respirator. DISCUSSION: These results suggest that ozone is a feasible strategy to disinfect N95 respirators for reuse during this and future pandemics.

Structure of the Francisella response regulator QseB receiver domain, and characterization of QseB inhibition by antibiofilm 2-aminoimidazole-based compounds.

With antibiotic resistance increasing at alarming rates, targets for new antimicrobial therapies must be identified. A particularly promising target is the bacterial two-component system. Two-component systems allow bacteria to detect, evaluate and protect themselves against changes in the environment, such as exposure to antibiotics and also to trigger production of virulence factors. Drugs that target the response regulator portion of two-component systems represent a potent new approach so far unexploited. Here, we focus efforts on the highly virulent bacterium Francisella tularensis tularensis. Francisella contains only three response regulators, making it an ideal system to study. In this study, we initially present the structure of the N-terminal domain of QseB, the response regulator responsible for biofilm formation. Subsequently, using binding assays, computational docking and cellular studies, we show that QseB interacts with2-aminoimidazole based compounds that impede its function. This information will assist in tailoring compounds to act as adjuvants that will enhance the effect of antibiotics.

Marine sponge alkaloids as a source of anti-bacterial adjuvants.

Novel approaches that do not rely upon developing microbicidal compounds are sorely needed to combat multidrug resistant (MDR) bacteria. The potential of marine secondary metabolites to serve as a source of non-traditional anti-bacterial agents is demonstrated by showing that pyrrole-imidazole alkaloids inhibit biofilm formation and suppress antibiotic resistance.

Evaluation of ethyl N-(2-phenethyl) carbamate analogues as biofilm inhibitors of methicillin resistant Staphylococcus aureus.

A small molecule library consisting of 45 compounds was synthesized based on the bacterial metabolite ethyl N-(2-phenethyl) carbamate. Screening of the compounds revealed a potent analogue capabale of inhibiting several strains of Methicillin Resistant S. aureus biofilms with low to moderate micromolar IC50 values.

Potentiation of Francisella Resistance to Conventional Antibiotics through Small Molecule Adjuvants.

A screen of 20 compounds identified small molecule adjuvants capable of potentiating anitbiotic activty against Francisella philomiragia. Analogue synthesis of an initial hit compound led to the discovery of a potentially new class of small molecule adjuvants containg an indole core. The lead compound was able to lower the MIC of colistin by 32-fold against intrinsically resistant F. philomiragia.

Potentiation of the Fosmidomycin analogue FR 900098 with substituted 2-oxazolines against Francisella novicida.

A library of 33 compounds was screened for potentiation of the antibiotic FR 900098 against the Francisella tularensis surrogate Francisella novicida. From the screen a highly potent 2-oxazoline adjuvant was discovered capable of potentiating FR 900098 with a 1000-fold reduction in MIC against the Francisella sub-species F. novicida and F. philomiragia.

Aryl amide small-molecule inhibitors of microRNA miR-21 function.

MicroRNAs (miRNAs) are single stranded RNA molecules of ∼22 nucleotides that negatively regulate gene expression. MiRNAs are involved in fundamental cellular processes, such as development, differentiation, proliferation, and survival. MiRNA misregulation has been linked to various human diseases, most notably cancer. MicroRNA-21 (miR-21), a well-established oncomiR, is significantly overexpressed in many types of human cancers, thus rendering miR-21 a potential therapeutic target. Using a luciferase-based reporter assay under the control of miR-21 expression, a high-throughput screen of >300,000 compounds led to the discovery of a new aryl amide class of small-molecule miR-21 inhibitors. Structure-activity relationship (SAR) studies resulted in the development of four aryl amide derivatives as potent and selective miR-21 inhibitors. The intracellular levels of various miRNAs in HeLa cells were analyzed by qRT-PCR revealing specificity for miR-21 inhibition over other miRNAs. Additionally, preliminary mechanism of action studies propose a different mode of action compared to previously reported miR-21 inhibitors, thus affording a new chemical probe for future studies.

Optical and physical characterization of a local evanescent array coupled biosensor: Use of evanescent field perturbations for multianalyte sensing.

The evanescent field surrounding the core of an optical waveguide is very sensitive to refractive index changes near the core. This sensitivity can be exploited to form the basis for a quantitative sensor with high specificity and sensitivity. Selective probe molecules may be attached to the surface of a waveguide core and the evanescent field locally monitored as target analytes are introduced to the system. In this study, probe/analyte regions were simulated using lithographically patterned organic films with thicknesses of 60 nm and 130 nm. The evanescent field strength was measured quantitatively using near field scanning optical microscopy (NSOM). The presence of the organic material on the waveguide caused up to a 70% change in the intensity of the evanescent field over the patterned region and the excitation of a weakly bound higher order mode. The waveguide core and surrounding cladding were numerically simulated using the beam propagation method and these predictions are in quantitative agreement with the experimental results obtained using NSOM.

Evanescent field response to immunoassay layer thickness on planar waveguides.

The response of a compact photonic immunoassay biosensor based on a planar waveguide to variation in antigen (C-reactive protein) concentration as well as waveguide ridge height has been investigated. Near-field scanning optical microscope measurements indicate 1.7%nm and 3.3%nm top surface optical intensity modulation due to changes in effective adlayer thickness on waveguides with 16.5 and 10 nm ridge heights, respectively. Beam propagation method simulations are in good agreement with the experimental sensitivities as well as the observation of leaky mode interference both within and after the adlayer region.