Understanding the mechanisms of antimicrobial resistance (AMR) will help launch a counter-offensive against human pathogens that threaten our ability to effectively treat common infections. Herein, we report bis(4-nitrobenzyl)sulfanes, which are activated by a bacterial enzyme to produce hydrogen sulfide (H2S) gas. We found that H2S helps maintain redox homeostasis and protects bacteria against antibiotic-triggered oxidative stress “on demand”, through activation of alternate respiratory oxidases and cellular antioxidants. We discovered, a hitherto unknown role for this gas, that chemical inhibition of H2S biosynthesis reversed antibiotic resistance in multidrug-resistant (MDR) uropathogenic Escherichia coli strains of clinical origin, whereas exposure to the H2S donor restored drug tolerance. Together, our study provides a greater insight into the dynamic defence mechanisms of this gas, modes of antibiotic action as well as resistance while progressing towards new pharmacological targets to address AMR.
Fluorescent silver nanoparticles have been employed in an immunoassay to detect HIV p24 antigen with high sensitivity in the linear range of 10–1000 pg mL−1.
We have engineered streptavidin labelled Europium doped fluorescent silica nanoparticles which significantly increased sensitivity without compromising the specificity of the immunoassay. As a proof of concept, a time resolved fluorescence based sandwich immunoassay was developed to detect HIV-1 p24 antigen in clinical specimens. The detection range of the silica nanoparticle based immunoassay (SNIA) was found to be between 0.02 to 500 pg/mL in a linear dose dependent manner. SNIA offers 1000 fold enhancement over conventional colorimetric ELISA. Testing of plasma samples that were HIV negative showed no false positive results in the detection of HIV-1 p24 antigen. This highly sensitive p24 assay can help improve blood safety by reducing the antibody negative window period in blood donors in resource limited settings where nucleic acid testing is not practical or feasible. This technology can also be easily transferred to a lab-on-a-chip platform for use in resource limited settings and can also be easily adopted for the detection of other antigens.
Background: We evaluated the Surveillance of Surgical Site Infection (SSI), Auditing, and Feedback (SAF) effect on the rate of compliance with an SSI care bundle and measured its effectiveness in reducing the SSI rate. Method: A prospective cohort study from January 2014 to December 2016 was classified into three phases: pre-SAF, early-SAF, and late-SAF. Pre-operative baseline characteristics of 24,677 patients who underwent orthopedic, cardiovascular thoracic surgery (CTVS) or urologic operations were recorded. Univariable analyses of the SSI rates in the pre-SAF and post-SAF phases were performed. Percentage compliance and non-compliance with each care component were calculated. Correlation between reduction in the SSI rate and increase in compliance with the pre-operative, peri-operative, and post-operative care-bundle components was performed using the Spearman test. Results: There was a significant decrease in the SSI rate in orthopedic procedures that involved surgical implantation and in mitral valve/aortic valve (MVR/AVR) cardiac operations, with a relative risk (RR) ratio of 0.19 (95% confidence interval [CI] 0.12–0.31) and 0.08 (95% CI 0.03–0.22), respectively. The SSI rate was inversely correlated with the rate of compliance with pre-operative (r = -0.738; p = 0.037), peri-operative (r = - 0.802; p = 0.017), and post-operative (r = -0.762; p = 0.028) care bundles. Conclusion: Implementation of the Surveillance of SSI, Auditing, and Feedback bundle had a profound beneficial effect on the SSI rate, thereby reducing healthcare costs and improving patient quality of life.