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Inferring Mycobacterium tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China

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Biomedical and Environmental Sciences 2024年第2期37卷 157-169页

作者： FAN Yu Feng LIU Dong Xin CHEN Yi Wang OU Xi Chao MAO Qi Zhi YANG Ting Ting WANG Xi Jiang HE Wen Cong ZHAO Bing LIU Zhen Jiang ABULIMITI Maiweilanjiang AIHEMUTI Maimaitiaili GAO Qian ZHAO Yan Lin Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China National tuberculosis Reference Laboratory Chinese Center for Disease Control and PreventionBeijing 102206China Hangzhou Red Cross Hospital Hangzhou 310005ZhejiangChina Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention Urumqi 830026XinjiangChina tuberculosis Dispensary of Kashgar Prefecture Kashgar 844099XinjiangChina

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health *** Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in ***,molecular epidemiological studies of Kashgar are *** A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission *** A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated *** resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,Ptuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB *** Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

关键词： Mycobacterium tuberculosis Whole-genome sequencing(WGS) Transmission Drug resistance Xinjiang

Recent progresses of exosome-liposome fusions in drug delivery

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Chinese Chemical Letters 2024年第2期35卷 107-117页

作者： Lulu Zheng Bo Hu Deyao Zhao Wenjing Liu Qing Liu Yuanyu Huang Shaobo Ruan School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Department of Radiation Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Beijing Key Laboratory of Drug Resistance tuberculosis Research Beijing Tuberculosis and Thoracic Tumor Research Instituteand Beijing Chest HospitalCapital Medical UniversityBeijing 101149China

Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all *** to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past ***,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide ***,the emerging exosome-liposome fusion strategy has become a potential approach to solve such ***,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease *** review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational *** current challenge and future perspective regarding their clinical translation and application will also be discussed.

关键词： Exosome Liposome Membrane fusion Drug delivery Disease treatment

Antimicrobial Resistance Analysis and Whole-Genome Sequencing of Salmonella Isolates from Environmental Sewage — Guangzhou City, Guangdong Province, China, 2022–2023

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China CDC weekly 2024年第13期6卷 254-260页

作者： Bihui Su Guanghong Du Shuiping Hou Zongqiu Chen Xiaoying Wu Gang He Jun Yuan Chaojun Xie tuberculosis Management and Treatment Department Guangzhou Chest HospitalGuangzhou CityGuangdong ProvinceChina School of Public Health Guangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina Guangzhou Center for Disease Control and Prevention Guangzhou CityGuangdong ProvinceChina Office of the Director Huadu District Center for Disease Control and PreventionGuangzhou CityGuangdong ProvinceChina

What is already known about this topic?S.1,4,[5],12:i:-and *** are emerging serotypes of Salmonella that require close monitoring for antimicrobial resistance and containment of their *** is added by this report?The study aimed to identify antimicrobial resistance genes(ARGs)in S.1,4,[5],12:i:-and *** strains isolated from environmental sewage in Guangzhou City,Guangdong Province,China.A phylogenetic tree was constructed using single nucleotide polymorphism data to assess genetic relatedness among strains,offering insights for Salmonella infection outbreak investigations in the *** are the implications for public health practice?It is crucial to implement strategies,such as integrating different networks,to control the spread of drugresistant *** technologies must be utilized to disinfect sewage and eliminate *** food safety and proper sewage disinfection are essential to curb the dissemination of Salmonella.

关键词： Whole offering integrating

The virulence regulator AbsR in avian pathogenic Escherichia coli has pleiotropic effects on bacterial physiology

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Journal of Integrative Agriculture 2024年第2期23卷 649-668页

作者： Dongfang Zhao Haobo Zhang Xinyang Zhang Fengwei Jiang Yijing Li Wentong Cai Ganwu Li State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150038China National Animal tuberculosis Reference Laboratory Division of Zoonoses SurveillanceChina Animal Health and Epidemiology CenterQingdao 266032China Department of Veterinary Diagnostic and Production Animal Medicine College of Veterinary MedicineIowa State UniversityAmesIowa 50011-1134the United States

Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic ***(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and ***(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for ***,a deep understanding of the AbsR regulatory mechanism as well as its regulon is *** this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)*** found that AbsR directly regulates 99 genes and indirectly regulates 667 ***,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC ***,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC ***,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule ***,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.

关键词： avian pathogenic Escherichia coli(APEC) extraintestinal pathogenic Escherichia coli(ExPEC) AbsR RNA-Seq ChIP-Seq gene regulation

Alkaline sphingomyelinase deficiency impairs intestinal mucosal barrier integrity and reduces antioxidant capacity in dextran sulfate sodium-induced colitis

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World Journal of Gastroenterology 2024年第10期30卷 1405-1419页

作者： Ye Tian Xin Li Xu Wang Si-Ting Pei Hong-Xin Pan Yu-Qi Cheng Yi-Chen Li Wen-Ting Cao Jin-Dong Ding Petersen Ping Zhang International School of Public Health and One Health Hainan Medical UniversityHaikou 571199Hainan ProvinceChina Medical Laboratory Science and Technology College Harbin Medical University-Daqing CampusDaqing 163000Heilongjiang ProvinceChina Department of Laboratory Diagnosis Qiqihar Tuberculosis Control CenterQiqihar 161000Heilongjiang ProvinceChina Department of Public Health University of CopenhagenCopenhagen 1353Denmark Department of Public Health University of Southern DenmarkOdense 5000Denmark

BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown *** sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory ***,the underlying mechanism is still *** To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced *** Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of *** permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum *** epithelial cell ultrastructure was observed by electron *** blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,*** oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress *** Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS *** mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS *** observations revealed progressive damage to the tight junctions of intestinal epithelial ***,by day 4,mitochondria appeared swollen and ***,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly *** expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decr

关键词： Alkaline sphingomyelinase Intestinal mucosal barrier Antioxidant capacity Dextran sulfate sodium-induced colitis nuclear factor erythroid 2-related factor 2

Design,synthesis,and biological evaluation of 1,2,4-triazole derivatives as potent antitubercular agents

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Chinese Chemical Letters 2024年第3期35卷 326-331页

作者： Yu Wen Shichun Lun Yuxue Jiao Wei Zhang Tianyu Hu Ting Liu Fan Yang Jie Tang Bing Zhang William R.Bishai Li-Fang Yu Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China Center for tuberculosis Research Department of MedicineDivision of Infectious DiseaseJohns Hopkins School of MedicineBaltimoreMD21231-1044United States Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Shanghai Key Laboratory of Green Chemistry and Chemical Process School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China

Inhibition of mycobacterial membrane protein large 3(MmpL3)thereby affecting the mycolic acid biosynthetic pathway has been proven to be an effective strategy for developing antitubercular *** on the X-ray crystal structure of MmpL3 inhibitor complexes,a series of novel 1,2,4-triazole derivatives were designed,synthesized and evaluated antitubercular activity against Mtb strain *** structure–activity relationship exploration resulted in the identification of compounds 21 and 28,which possess potent antitubercular activity against Mtb strain H37Rv[minimum inhibitory concentration(MIC)=0.03–0.13μg/mL]and the clinical isolates of multidrug resistance(MDR)and extensive drug resistance(XDR)tuberculosis(MIC=0.06–1.0μg/mL).Moreover,compounds 21 and 28 showed neglectable cytotoxicity(IC_(50)≥32μg/mL)to the mammalian Vero cells and favorable physicochemical and pharmacokinetic properties according to the in silico absorption,distribution,metabolism and excretion(ADME)***,the potential target of representative 1,2,4-triazole 28 was identified to be MmpL3 using a microscale thermophoresis(MST)assay.

关键词： tuberculosis MDR and XDR-TB MmpL3 inhibitor 1 2 4-Triazole Structure-based drug design

Multichannel Financing Reduces Economic Burden and Improves the Medical Security Level for tuberculosis Patients

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China CDC weekly 2020年第12期2卷 194-197页

作者： Fei Huang Ni Wang You Li Hui Zhang Yanli Yuan Xiaomeng Wang Xiaolin Wang Shitong Huan Lixia Wang Mingting Chen Yanlin Zhao National Center for tuberculosis Control and Prevention China Center for Disease Control and PreventionBeijingChina Jilin Provincial Center for tuberculosis Control and Prevention ChangchunJilinChina Zhejiang Provincial Center for tuberculosis Control and Prevention HangzhouZhejiangChina Ningxia Hui Autonomous Region tuberculosis Dispensary YinchuanNingxia Hui Autonomous RegionChina Bill&Melinda Gates foundation Beijing officeBeijingChina

tuberculosis(TB)is one of the main infectious diseases to simultaneously cause poverty and be caused by *** the economic burden of TB patients in China is essential to improving patient compliance and reducing the impact of the TB *** accordance with the national reform of the medical and health system and the current status of the country’s TB prevention and treatment service system,representatives of the government proposed the concept of a multichannel financing mechanism.

关键词： prevention tuberculosis diseases

Gastrointestinal tuberculosis:Diagnostic approaches for this uncommon pathology

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World Journal of Clinical Cases 2024年第23期12卷 5283-5287页

作者： Lottie Brown Michael Colwill Andrew Poullis Department of Gastroenterology St George's University Hospital NHS Foundation TrustLondon SW170QTUnited Kingdom

A case report entitled“Primary gastroduodenal tuberculosis presenting as gastric outlet obstruction”recently published in the World Journal of Clinical Cases presented a rare cause of gastric outlet obstruction and highlighted the atypical manner in which gastrointestinal tuberculosis(TB)can *** literature with regards to this rare pathology is limited to case reports and case series with the largest being published using data from between 2003 and ***,since then the diagnostic tools available have significantly changed with more modern and increasingly accurate tests now *** editorial reviews the current state of the art with regards to diagnosis in gastrointestinal TB.

关键词： Gastrointestinal tuberculosis Diagnostic approach Microbiology Serology Molecular diagnosis Infectious disease

Effects of Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes

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Military Medical Research 2020年第2期7卷 125-139页

作者： Wen-Ping Gong Yan Liang Yan-Bo Ling Jun-Xian Zhang You-Rong Yang Lan Wang Jie Wang Ying-Chang Shi Xue-Qiong Wu Army tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of tuberculosis Diagnosis and Treatment Institute for Tuberculosis Researchthe 8th Medical Center of Chinese PLA General HospitalBeijing 100091China

Background:tuberculosis is a leading cause of death *** is an effective vaccine,but not widely used in many parts of the world due to a variety of *** vaccae(***)is another vaccine used in human subjects to prevent *** the current study,we investigated the potential mechanisms of *** vaccination by determining differentially expressed genes in mice infected with *** before and after *** ***:Three days after exposure to *** H37 Rv strain(5×10~5 CFU),adult BALB/c mice randomly received either *** vaccine(22.5μg)or vehicle via intramuscular injection(n=8).Booster immunization was conducted 14 and 28 days after the primary *** expressed genes were identified by microarray followed by standard bioinformatics ***:*** vaccination provided protection against *** infection(most prominent in the lungs).We identified 2,326 upregulated and 2,221 downregulated genes in vaccinated *** changes could be mapped to a total of 123 signaling pathways(68 upregulated and 55 downregulated).Further analysis pinpointed to the MyD88-dependent TLR signaling pathway and PI3 K-Akt signaling pathway as most likely to be ***:*** vaccine provided good protection in mice against *** infection,via a highly complex set of molecular *** findings may provide clue to guide development of more effective vaccine against tuberculosis.

关键词： Mycobacterium tuberculosis Immunotherapeutic effect Immunotherapy Vaccae vaccine Differentially expressed genes Signaling pathway