Centro Nacional de Biotecnología, CSIC, 28043 Madrid, Spain.
Published: April 2023
AI Article Synopsis
Article Abstract
Understanding the consequences in bacterial physiology of the acquisition of drug resistance is needed to identify and exploit the weaknesses derived from it. One of them is collateral sensitivity, a potentially exploitable phenotype that, unfortunately, is not always conserved among different isolates. The identification of robust, conserved collateral sensitivity patterns is then relevant for the translation of this knowledge into clinical practice. We have previously identified a robust fosfomycin collateral sensitivity pattern of that emerged in different tobramycin-resistant clones. To go one step further, here, we studied if the acquisition of resistance to tobramycin is associated with robust collateral sensitivity to fosfomycin among isolates. To that aim, we analyzed, using adaptive laboratory evolution approaches, 23 different clinical isolates of presenting diverse mutational resistomes. Nine of them showed collateral sensitivity to fosfomycin, indicating that this phenotype is contingent on the genetic background. Interestingly, collateral sensitivity to fosfomycin was linked to a larger increase in tobramycin minimal inhibitory concentration. Further, we unveiled that low expression, rendering a higher intracellular accumulation of fosfomycin, and a reduction in the expression of the alternative peptidoglycan-recycling pathway enzymes, might be on the basis of the collateral sensitivity phenotype.
Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China; Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 20032, China. Electronic address:
Infectious diseases are extremely important public health issues, where the design of effective, rapid, and convenient detection platforms is critical. In this study, we coupled SuCas12a2, a novel Cas12 family RNA-targeting nuclease, with conventional PCR and recombinase polymerase amplification (RPA), respectively, to develop novel detection approaches, named PCR-SuCas12a2 and RPA-SuCas12a2. SuCas12a2 possesses collateral cleavage activity and cuts the additional single-stranded RNA (ssRNA) added to the reaction system once the ternary complex RNA-SuCas12a2-CRISPR RNA (crRNA) is formed.
Syzygioblanes A-C (-), isolated from the Indonesian traditional herbal medicine (), are meroterpenoids with a spiro ring formed through a [4 + 2] cycloaddition of the flavanone desmethoxymatteucinol with cyclic sesquiterpenoids. Our ongoing phytochemical investigation of resulted in the isolation of five additional spiro-meroterpenoids, syzygioblanes D-H (-), which are hybrids of the same flavanone with eudesmane/cadinane-type sesquiterpenoids. A possible biosynthetic pathway involves enzymatic dearomative hydroxylation of desmethoxymatteucinol followed by [4 + 2] cyclization of the resulting diene with a cyclic sesquiterpene containing an exocyclic methylene to form the unique spiro ring in the syzygioblane molecule.
Maintaining efficacy of human immunodeficiency virus (HIV) medications is challenging among children because of dosing difficulties, the limited number of approved drugs, and low rates of medication adherence. Drug level feedback (DLF) can support dose optimization and timely interventions to prevent treatment failure, but current tests are heavily instrumented and centralized. We developed the REverse-transcriptase ACTivity-crispR (REACTR) assay for rapid measurement of HIV drugs based on the extent of DNA synthesis by HIV reverse transcriptase.
Background: Cerebral hernia is a serious complication after thrombectomy in patients with acute ischemic stroke (AIS). This study aims to explore the predictive value of emergency preoperative plasma D-dimer levels in cerebral herniation after successful thrombectomy.
Methods: Between January 2019 and December 2023, patients with AIS who received a successful thrombectomy in our single comprehensive stroke center were retrospectively enrolled.
