Emerging infectious diseases, the persistent potential for destabilising pandemics, remain a global threat leading to excessive morbidity and mortality. The current outbreak of pneumonia caused by 2019 novel coronavirus (COVID-19) illustrated difficulties in lack of effective drugs for treatment. Accurate and rapid diagnostic tools are essential for early recognition and treatment of infectious diseases, allowing timely implementation of infection control, improved clinical care and other public health measures to stop the spread of the disease. CRISPR-Cas technology speed up the development of infectious disease diagnostics with high rapid and accurate. In this review, we summarise current advance regarding diverse CRISPR-Cas systems, including CRISPR-Cas9, CRISPR-Cas12 and CRISPR-Cas13, in the development of fast, accurate and portable diagnostic tests and highlight the potential of CRISPR-Cas13 in COVID-19 Pneumonia and other emerging infectious diseases diagnosis.
ARTICLE HISTORY
A total of 189 Acinetobacter baumannii isolates were collected in 2011 from a teaching hospital in Chongqing, China. Susceptibility data showed strains carrying integrons were significantly more resistant to all tested antibiotics that strains lacking integrons. Five types of gene cassettes belonging to class I integrons were identified in this study, and for the first time two types of gene cassettes belonging to class II integrons are reported. Most of the cassettes belong to a class I integron (136/144) encoding arr3, aacA4, dfrA17, aadA5, aadB, cat, blaOXA10, aadA1, aadA2, dfrA and aacC1. Isolates contained a class I gene cassette; AadA2-HP-dfrA was the prevalent strain in this hospital. A class II integron was detected in eight strains, which contained the type IV fimbriae expression regulatory gene pilR and sulfate adenylyltransferase, suggesting a possible role in multidrug resistance. The major epidemic strains from intensive care unit patients belong to international clone 2. In conclusion, the presence of integrons was significantly associated with multiple drug resistance of A. baumannii in this hospital, and class I integron isolates bearing AadA2-HP-dfrA were the prevalent strain in this hospital.
ObjectivesCRISPR-Cas13a system-based nucleic acid detection methods are reported to have rapid and sensitive DNA detection. However, the screening strategy for crRNAs that enables CRISPR-Cas13a single-base resolution DNA detection of human pathogens remains unclear.MethodsA combined rational design and target mutation-anchoring CRISPR RNA (crRNA) screening strategy was proposed.ResultsA set of crRNAs was found to enable the CRISPR-Cas13 system to dramatically distinguish fluroquinolone resistance mutations in clinically isolated Mycobacterium tuberculosis strains from the highly homologous wild type, with a signal ratio ranging from 8.29 to 38.22 in different mutation sites. For the evaluation of clinical performance using genomic DNA from clinically isolated M. tuberculosis, the specificity and sensitivity were 100 and 91.4%, respectively, compared with culture-based phenotypic assays.ConclusionThese results demonstrated that the CRISPR-Cas13a system has potential for use in single nucleotide polymorphism (SNP) detection after tuning crRNAs. We believe this crRNA screening strategy will be used extensively for early drug resistance monitoring and guidance for clinical treatment.
Lysine glutarylation (Kglu) is a newly discovered post-translational modification (PTM), which is considered to be reversible, dynamic, and conserved in prokaryotes and eukaryotes. Recent developments in the identification of Kglu by mass spectrometry have shown that Kglu is mainly involved in the regulation of metabolism, oxidative damage, chromatin dynamics and is associated with various diseases. In this review, we firstly summarize the development history of glutarylation, the biochemical processes of glutarylation and deglutarylation. Then we focus on the pathophysiological functions such as glutaric acidemia 1, asthenospermia, etc. Finally, the current computational tools for predicting glutarylation sites are discussed. These emerging findings point to new functions for lysine glutarylation and related enzymes, and also highlight the mechanisms by which glutarylation regulates diverse cellular processes.
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