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2. Methodological Evaluation of Carbapenemase Detection by Different Methods

Author

Gao Nana, Zhou Jing, Li Ge, Liu Runde, Lu Guoping, and Shen Jilu

Subjects
rapid detection, wsg, detectr, methodological evaluation, Genetics, QH426-470, Microbiology, QR1-502
Abstract

The global proliferation of carbapenemase-producing bacteria (CPB) has garnered significant attention worldwide. Early diagnosis of CPB and accurate identification of carbapenemases are crucial for preventing the spread of CPB and ensuring targeted antibiotic therapy. Therefore, efficient and accurate identification of carbapenemases is paramount in clinically treating diseases associated with CPB. In this study, 58 CPB strains were collected and detected using the DNA endonuclease-targeted CRISPR trans reporter (DETECTR) method, a rapid detection platform based on CRISPR-Cas12a gene editing and isothermal amplification. Additionally, four conventional methods (the APB/EDTA method, PCR, NG-test Carba 5, and GeneXpert Carba-R) were employed and compared against whole genome sequencing (WGS) results, considered the gold standard, to evaluate their efficacy in detecting carbapenemases. Detection by the APB/EDTA method revealed that 29 strains were positive for Class A serine endopeptidases, while 29 strains were positive for Class B metalloenzymes. The classification of these zymotypes was consistent with the sequencing result. All target carbapenemases for KPC were identified with 100% sensitivity using NG-test Carba 5, PCR, DETECTR, and GeneXpert Carba-R. In the case of NDM, both Xpert Carba-R and DETECTR showed a sensitivity of 100%. In contrast, NG-test Carba 5 and PCR had a slightly lower sensitivity of 96.7%, each missing one target carbapenemase. n this study, the APB/EDTA method is capable of identifying the zymotype classification but not the specific resistant genes, while Xpert Carba-R and DETECTR are able to detect all target carbapenemases.

Published
2024
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7. Molecular Evolution and Increasing Macrolide Resistance of Bordetella pertussis, Shanghai, China, 2016-2022

Author

Fu, Pan, Zhou, Jinlan, Yang, Chao, Nijiati, Yaxier, Zhou, Lijun, Yan, Gangfen, Lu, Guoping, Zhai, Xiaowen, and Wang, Chuanqing

Subjects
Nucleotide sequencing -- Analysis -- Genetic aspects, Genomics -- Analysis -- Genetic aspects, Genetic research -- Analysis -- Genetic aspects, Genes -- Genetic aspects -- Analysis, Drug resistance in microorganisms -- Genetic aspects, DNA sequencing -- Analysis -- Genetic aspects, Genomes -- Genetic aspects -- Analysis, Infants -- Analysis, Bordetella pertussis -- Genetic aspects -- Analysis, Public health -- Analysis, RNA -- Analysis -- Genetic aspects, Evolutionary biology -- Genetic aspects -- Analysis, Health
Abstract

Whooping cough (pertussis) is a contagious respiratory illness caused by Bordetella pertussis. The introduction of the whole-cell vaccine (WCV) successfully decreased the incidence of pertussis. Although vaccination has been successful, [...]

Published
2024
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8. The nuclear cytokine IL-37a controls lethal cytokine storms primarily via IL-1R8-independent transcriptional upregulation of PPARγ

Author

Wei, Rongfei, Han, Xiao, Li, Mengyuan, Ji, Yuan, Zhang, Lianfeng, Christodoulou, Maria-Ioanna, Hameed Aga, Najwa Jameel, Zhang, Caiyan, Gao, Ran, Liu, Jiangning, Fu, Jinrong, Lu, Guoping, Xiao, Xiaojun, Liu, Xiaoyu, Yang, Ping-Chang, McInnes, Iain B., Sun, Ying, Gao, Peisong, Qin, Chuan, Huang, Shau-Ku, Zhou, Yufeng, and Xu, Damo

Published
2023
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27. A retrospective study of the efficacy and safety of levofloxacin in children with severe infection

Author

Zhang Junqi, Cai Jie, Wang Jinglin, Lu Jinmiao, Lu Guoping, Wang Yi, and Li Zhiping

Subjects
levofloxacin, quinolone, children, infection, PICU, Pediatrics, RJ1-570
Abstract

ObjectivesLevofloxacin is widely used because of its broad-spectrum antimicrobial activity and convenient dosing schedule. However, the relevance of its use in children remains to be investigated. The purpose of this study is to investigate the efficacy and safety of levofloxacin use in children with severe infections.MethodsWe conducted a retrospective observational study of patients

Published
2024
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28. Itaconate inhibits TET DNA dioxygenases to dampen inflammatory responses

Author

Chen, Lei-Lei, Morcelle, Carmen, Cheng, Zhou-Li, Chen, Xiufei, Xu, Yanping, Gao, Yajing, Song, Junbin, Li, Zhijun, Smith, Matthew D, Shi, Miao, Zhu, Yezhang, Zhou, Neng, Cheng, Meng, He, Chenxi, Liu, Kwei‐Yan, Lu, Guoping, Zhang, Lei, Zhang, Cheng, Zhang, Jinye, Sun, Yiping, Qi, Tuan, Lyu, Yingying, Ren, Zhi-Zhong, Tan, Xian-Ming, Yin, Jiayong, Lan, Fei, Liu, Ying, Yang, Hui, Qian, Maoxiang, Duan, Caiwen, Chang, Xing, Zhou, Yufeng, Shen, Li, Baldwin, Albert S, Guan, Kun-Liang, Xiong, Yue, and Ye, Dan

Subjects
Biochemistry and Cell Biology, Biological Sciences, Lung, Rare Diseases, Genetics, Animals, DNA, Dioxygenases, Lipopolysaccharides, Mice, Succinates, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

As one of the most induced genes in activated macrophages, immune-responsive gene 1 (IRG1) encodes a mitochondrial metabolic enzyme catalysing the production of itaconic acid (ITA). Although ITA has an anti-inflammatory property, the underlying mechanisms are not fully understood. Here we show that ITA is a potent inhibitor of the TET-family DNA dioxygenases. ITA binds to the same site on TET2 as the co-substrate α-ketoglutarate, inhibiting TET2 catalytic activity. Lipopolysaccharide treatment, which induces Irg1 expression and ITA accumulation, inhibits Tet activity in macrophages. Transcriptome analysis reveals that TET2 is a major target of ITA in suppressing lipopolysaccharide-induced genes, including those regulated by the NF-κB and STAT signalling pathways. In vivo, ITA decreases the levels of 5-hydroxymethylcytosine, reduces lipopolysaccharide-induced acute pulmonary oedema as well as lung and liver injury, and protects mice against lethal endotoxaemia, depending on the catalytic activity of Tet2. Our study thus identifies ITA as an immune modulatory metabolite that selectively inhibits TET enzymes to dampen the inflammatory responses.

Published
2022

36. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice

Author

Wang Chuanqing, Yin Lijun, Fu Pan, Lu Guoping, Zhai Xiaowen, and Yang Changsheng

Subjects
apoe23, sepsis, salmonella typhimurium, lps, ldlr, lrp, Medicine
Abstract

Two independent experiments were performed with three groups each (sepsis control, sepsis, and sepsis with apoE23 treatment) to investigate the anti-inflammatory effect of apolipoprotein 23 (apoE23) in a mouse model of sepsis induced by S. typhimurium. Survival rates; plasma level variations in tumor necrosis factor (TNF)-α, interleukin (IL)-6, and lipopolysaccharide (LPS); S. typhimurium colony-forming units in the spleen tissue; and mRNA and protein expression levels of low-density lipoprotein receptor (LDLR), LDLR-related protein (LRP), syndecan-1, and scavenger receptor B1 were evaluated in the livers of mice from the three groups. Results found that the survival rate of septic mice treated with apoE23 was 100% within 48 h, while it was only 40% in septic mice without apoE23 treatment (P < 0.001). The plasma LPS, TNF-α, and IL-6 levels and the S. typhimurium load in mice in the apoE23-treated group were significantly lower than those in septic mice (P < 0.05). Moreover, apoE23 restored the downregulated expression of LDLR and LRP in the liver tissue of septic mice. So apoE23 exhibits an anti-inflammatory effect in the mouse model of S. typhimurium-induced sepsis. Further studies are required to understand the mechanisms underlying the anti-inflammatory effects of apoE23.

Published
2023
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