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Newly Detected Transmission of bla_(KPC-2) by outer membrane vesicles in Klebsiella Pneumoniae

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Current Medical Science 2023年第1期43卷 80-85页

作者： Liu-jun CHEN Xiao-peng JING Dong-li MENG Ting-ting WU Huan ZHOU Rui-ling SUN Xiao-chun MIN Rong LIU Ji ZENG Department of Clinical Laboratory Wuhan Fourth HospitalWuhan430030China Key Laboratory of Ministry of Education for Neurological Disorders Department of PathophysiologySchool of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health *** is mainly caused by the plasmid-carried carbapenemase *** membrane vesicles(OMVs)contain toxins and other factors involved in various biological processes,includingβ-lactamase and antibiotic-resistance *** study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella(K.)*** We selected CR-KP producing *** carbapenemase-2(KPC-2)to study whether they can transfer resistance genes through *** OMVs of CR-KP were obtained by ultracentrifugation,and incubated with carbapenem-sensitive *** for 4 ***,the carbapenem-sensitive *** was tested for the presence of bla_(KPC-2)resistance gene and its sensitivity to carbapenem *** The existence of OMVs was observed by the electron *** extracted OMVs had bla_(KPC-2)resistance *** incubation with OMVs,bla_(KPC-2)resistance gene was detected in sensitive ***,and it became resistant to imipenem and *** This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_(KPC-2)to sensitive ***,allowing the bacteria to produce carbapenemase,which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.

关键词： bla_(KPC-2) carbapenem-resistant Klebsiella pneumoniae carbapenemase outer membrane vesicles simplified carbapenem inactivation method

Role of outer membrane vesicles in Bacterial Physiology and Host Cell Interactions

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Infectious Microbes & Diseases 2020年第1期2卷 3-9页

作者： Lingyu Gao Stijn van der Veen Department of Microbiology and Parasitology School of MedicineZhejiang UniversityHangzhouChina State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Department of Dermatology Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouChina.

outer membrane vesicles(OMVs)are spherical particles shed from the outer membrane of Gram-negative bacteria,which contain the typical components present in the outer membrane,although enrichment of specific molecules may occur,and furthermore a variety of periplasmic components and occasionally some inner membrane or cytoplasmic *** the detailed mechanisms of OMV biogenesis are not fully illuminated yet,several models have been proposed that demonstrate OMV biogenesis is an orchestrated well-regulated *** secretion offers a way for both intra-and inter-species bacterial communication and for interaction or modulation of the bacterial ***,OMVs have proven to be functionally versatile and important for bacterial physiology and survival of the host *** the host,OMVs are internalized via host cell endocytosis pathways,allowing them to subsequently trigger a variety of cellular *** this review,we discuss the recent advances in establishing the mechanisms involved in OMV biogenesis and the impact of OMVs on bacterial physiology and intracellular modulation of the host.

关键词： endocytosis OMP OMV outer membrane vesicles secretion system virulence factors

Personalized cancer vaccines from bacteria-derived outer membrane vesicles with antibody-mediated persistent uptake by dendritic cells

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Fundamental Research 2022年第1期2卷 23-36页

作者： Jie Liang Keman Cheng Yao Li Jiaqi Xu Yiwei Chen Nana Ma Qingqing Feng Fei Zhu Xiaotu Ma Tianjiao Zhang Yale Yue Guangna Liu Xinjing Guo Zhiqiang Chen Xinwei Wang Ruifang Zhao Ying Zhao Jian Shi Xiao Zhao Guangjun Nie CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China IGDB-NCNST Joint Research Center Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Nanocarriers with intrinsic immune adjuvant properties can activate the innate immune system while delivering tumor antigen,thus efficiently facilitating antitumor adaptive ***-derived outer membrane vesicles(OMVs)are an excellent candidate due to their abundance of pathogen associated molecular ***,during the uptake of OMVs by dendritic cells(DCs),the interaction between lipopolysaccharide and toll-like receptor 4 induces rapid DC maturation and uptake blockage,a phenomenon we refer to as“maturation-induced uptake obstruction"(MUO).Herein we decorated OMV with the DC-targeting aDEC205 antibody(OMV-DEC),which endowed the nanovaccine with an uptake mechanism termed as 4

关键词： Tumor vaccine outer membrane vesicles Antibody modification Antigen display Dendritic cell uptake Myeloid derived suppressor cells

outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation:a potential new mechanism for diabetic kidney disease

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Outer membrane vesicles derived from gut microbiota mediate ...

The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions

浙江省免疫学会第十三次学术大会

作者： Peipei Chen Kunling Ma Department of Nephrology the Second Affiliated HospitalSchool of MedicineZhejiang University

Background:Chronic tubulointerstitial inflammation is a common pathological process in diabetic kidney disease(DKD).However,its underlying mechanism is largely ***:This study aims to investigate the role of gut microbiota-derived outer membrane vesicles(OMVs) in tubulointerstitial inflammation in *** and methods:Gut microbiota in diabetes mellitus(DM) rats was manipulated by microbiota depletion and fecal microbiota transplantation(FMT) to explore its role in tubulointerstitial *** check the direct effects of OMVs,fecal bacterial extracellular vesicles(fBEVs) were administrated to mice orally and HK-2 cells in *** mechanistic investigations,HK-2 cells were treated with small interfering RNA against Caspase 4 and fBEVs pre-neutralized by polymyxin B(PMB).Results:The increased levels of serum cytokines,upregulated expression levels of inflammatory proteins in the renal cortex and tubular pathological injuries were observed in DM rats,which were alleviated by gut microbiota depletion and FMT treatment,indicating that gut microbiota was involved in systemic and tubulointerstitial inflammation in *** diabetic rats,gut microbiota-derived OMVs were increased and were clearly detected in distant renal tubulointerstitium,which were reduced by gut microbiota depletion and FMT *** was suggested that increased gut microbiota-derived OMVs might be involved in the pathogenesis and progression of *** expression levels of occludin and zona occludens 1 in the colon of DM rats decreased,accompanied by much more OMVs infiltration in *** microbiota depletion and FMT treatment could reverse these *** addition,orally treated DiD-fBEVs could be detected in distant tubulointerstitium of intestine-damaged *** was indicated that gut microbiota-derived OMVs could translocate through disrupted gut barrier into the ***-fBEVs directly administered by gavage translocated into tubular epithel

关键词： diabetic kidney disease renal tubulointerstitial inflammation gut microbiota outer membrane vesicles Caspase 11 pathway

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1560-1591页

作者： Yu Fu Jia Li Wenyun Cai Yulan Huang Xinlong Liu Zhongyi Ma Zhongjie Tang Xufei Bian Ji Zheng Jiayun Jiang Chong Li Medical Research Institute College of Pharmaceutical SciencesSouthwest UniversityChongqing 400715China Institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Urology Urologic Surgery CenterXinqiao HospitalThird Military Medical University(Army Medical University)Chongqing 400037China

Intratumoral microbiota has become research hotspots,and emerges as a non-negligent new component of tumor microenvironments(TME),due to its powerful infuence on tumor initiation,metas-tasis,immunosurveillance and prognosis despite in *** accumulations of microbes,and their related components and metabolites within tumor tissues,endow TME with additional pluralistic features which are distinct from the conventional ***,it's definitely necessary to comprehen-sively delineate the sophisticated landscapes of tumor microbe microenvironment,as well as their func-tions and related underlying ***,in this review,we focused on the fields of tumor microbe microenvironment,including the heterogeneity of intratumor microbiota in different types of tu-mors,the controversial roles of intratumoral microbiota,the basic features of tumor microbe microenvi-ronment(i.e.,pathogen-associated molecular patterns(PAMPs),typical microbial metabolites,autophagy,infammation,multi-faceted immunomodulation and chemoresistance),as well as the multi-disciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes,microbiota metabolites,antibiotics,synthetic biology and rationally de-signed *** hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial,and facilitate the development of microbes-based tumor-specific treatments.

关键词： Tumor microbe microenvironment Microbiota metabolites Immunomodulation Chemoresistance Multidisciplinary approach Genetically engineered microbiota Autophagy outer membrane vesicles

Bacterial outer membrane vesicle-based cancer nanovaccines

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Cancer Biology & Medicine 2022年第9期19卷 1290-1300页

作者： Xiaoyu Gao Qingqing Feng Jing Wang Xiao Zhao CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety&CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of ChinaBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Center of Drug Evaluation National Medical Products AdministrationBeijing 100022China IGDB-NCNST Joint Research Center Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Tumor vaccines,a type of personalized tumor immunotherapy,have developed rapidly in recent *** vaccines evoke tumor antigen-specific T cells to achieve immune recognition and killing of tumor *** the immunogenicity of tumor antigens alone is insufficient,immune adjuvants and nanocarriers are often required to enhance anti-tumor immune *** present,vaccine carrier development often integrates nanocarriers and immune *** them,outer membrane vesicles(OMVs)are receiving increasing attention as a delivery platform for tumor *** are natural nanovesicles derived from Gramnegative bacteria,which have adjuvant function because they contain pathogen associated molecular ***,OMVs can be functionally modified by genetic engineering of bacteria,thus laying a foundation for applications as a delivery platform for tumor *** review summarizes 5 aspects of recent progress in,and future development of,OMV-based tumor nanovaccines:strain selection,heterogeneity,tumor antigen loading,immunogenicity and safety,and mass production of OMVs.

关键词： Cancer cancer vaccines outer membrane vesicles nanocarriers tumor antigen

Salmonella-mediated blood-brain barrier penetration,tumor homing and tumor microenvironment regulation for enhanced chemo/bacterial glioma therapy

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Acta Pharmaceutica Sinica B 2023年第2期13卷 819-833页

作者： Ze Mi Qing Yao Yan Qi Jinhai Zheng Jiahao Liu Zhenguo Liu Hongpei Tan Xiaoqian Ma Wenhu Zhou Pengfei Rong Department of Radiology The Third Xiangya HospitalCentral South UniversityChangsha 410013China Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China Department of Pathology Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of MedicineShihezi 832003China Key Laboratory of Biological Nanotechnology of National Health Commission Changsha 410082China School of Biomedical Sciences Hunan UniversityChangsha 410082China Department of Pathology Cangzhou Central Hospital&the Affiliated to Hebei Medical UniversityCangzhou 062650China

Chemotherapy is an important adjuvant treatment of glioma,while the efficacy is far from satisfactory,due not only to the biological barriers of blood-brain barrier(BBB)and blood-tumor barrier(BTB)but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as upregulation of P-glycoprotein(P-gp).To address these limitations,we report a bacteria-based drug delivery strategy for BBB/BTB transportation,glioma targeting,and *** selectively colonized into hypoxic tumor region and modulated tumor microenvironment,including macrophages repolarization and neutrophils ***,tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin(DOX)-loaded bacterial outer membrane vesicles(OMVs/DOX).By virtue of the surface pathogen-associated molecular patterns derived from native bacteria,OMVs/DOX could be selectively recognized by neutrophils,thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting ***,the P-gp expression on tumor cells was silenced by bacteria typeⅢsecretion effector to sensitize the efficacy of DOX,resulting in complete tumor eradication with 100%survival of all treated *** addition,the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk,and cardiotoxicity of DOX was also avoided,achieving excellent *** work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.

关键词： Glioma Neutrophil hitchhiking Blood-brain barrier Chemo-sensitization outer membrane vesicles Doxorubicin P-glycoprotein Salmonella

Bacterial extracellular vesicle applications in cancer immunotherapy

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Bioactive Materials 2023年第4期22卷 551-566页

作者： Kanika Suri Anisha D’Souza Di Huang Aashray Bhavsar Mansoor Amiji Department of Bioengineering College of EngineeringNortheastern UniversityBostonMA02115USA Department of Pharmaceutical Sciences School of PharmacyNortheastern UniversityBostonMA02115USA Massachusetts Eye and Ear Infirmary Harvard Medical SchoolBostonMA20115USA Department of Chemical Engineering College of EngineeringNortheastern UniversityBostonMA02115USA

Cancer therapy is undergoing a paradigm shift toward immunotherapy focusing on various approaches to activate the host immune *** research to identify appropriate immune cells and activate anti-tumor immunity continues to expand,scientists are looking at microbial sources given their inherent ability to elicit an immune *** extracellular vesicles(BEVs)are actively studied to control systemic humoral and cellular immune responses instead of using whole microorganisms or other types of extracellular vesicles(EVs).BEVs also provide the opportunity as versatile drug delivery *** mammalian EVs,BEVs have already made it to the clinic with the meningococcal vaccine(Bexsero®).However,there are still many unanswered questions in the use of BEVs,especially for chronic systemically administered *** this review,we address the opportunities and challenges in the use of BEVs for cancer immunotherapy and provide an outlook towards development of BEV products that can ultimately translate to the clinic.

关键词： Cancer immunotherapy Bacterial extracellular vesicles membrane vesicles outer membrane vesicles Mammalian extracellular vesicles