Cell Surface最新文献_第8页

In vitro efficacy of relebactam versus avibactam against Mycobacterium abscessus complex 瑞巴坦与阿维巴坦抗脓肿分枝杆菌复合体的体外疗效比较

Cell Surface Pub Date : 2021-12-01 DOI: 10.1016/j.tcsw.2021.100064

James Harrison , John A. Weaver , Maya Desai , Jonathan A.G. Cox

{"title":"In vitro efficacy of relebactam versus avibactam against Mycobacterium abscessus complex","authors":"James Harrison , John A. Weaver , Maya Desai , Jonathan A.G. Cox","doi":"10.1016/j.tcsw.2021.100064","DOIUrl":"10.1016/j.tcsw.2021.100064","url":null,"abstract":"<div>Infections resulting from Mycobacterium abscessus are increasing in prevalence worldwide, with the greatest risk posed to patients with underlying respiratory conditions. Treatment for infections is difficult due to wide ranging intrinsic antimicrobial resistance, which is compounded by the existence of a range of subspecies within the M. abscessus complex, each with varying additional antimicrobial resistance profiles. Previously, the use of β-lactam/β-lactamase inhibitors within a combination therapy has been proposed as an effective treatment option for pulmonary M. abscessus infections. Here, we assess the in vitro efficacy of two non-β-lactam based inhibitors, relebactam and avibactam, as agents against M. abscessus with their respective partner drugs imipenem and ceftazidime, as well as in triplicate combinations with additional β-lactam antibiotics against the M. abscessus complex. We have shown that the commercially available ratio of imipenem to relebactam is the appropriate ratio for bactericidal activity against M. abscessus, whereas the ratio between ceftazidime and avibactam is redundant, due to inactivity of ceftazidime to inhibit the bacteria. We have identified that the use of imipenem and meropenem alongside either relebactam or avibactam yield low minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) for each M. abscessus subspecies, which are within the therapeutically achievable concentration ranges within the epithelial lining fluid of the lungs. We propose the implementation of imipenem with relebactam in place of stand-alone imipenem into the current treatment regime, alongside meropenem, as a future front-line treatment option for M. abscessus complex infections.</div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39564392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

The role of pectin phase separation in plant cell wall assembly and growth 果胶相分离在植物细胞壁组装和生长中的作用

Cell Surface Pub Date : 2021-12-01 DOI: 10.1016/j.tcsw.2021.100054

Kalina T. Haas , Raymond Wightman , Alexis Peaucelle , Herman Höfte

{"title":"The role of pectin phase separation in plant cell wall assembly and growth","authors":"Kalina T. Haas , Raymond Wightman , Alexis Peaucelle , Herman Höfte","doi":"10.1016/j.tcsw.2021.100054","DOIUrl":"10.1016/j.tcsw.2021.100054","url":null,"abstract":"<div>A rapidly increasing body of literature suggests that many biological processes are driven by phase separation within polymer mixtures. Liquid-liquid phase separation can lead to the formation of membrane-less organelles, which are thought to play a wide variety of roles in cell metabolism, gene regulation or signaling. One of the characteristics of these systems is that they are poised at phase transition boundaries, which makes them perfectly suited to elicit robust cellular responses to often very small changes in the cell’s “environment”. Recent observations suggest that, also in the semi-solid environment of plant cell walls, phase separation not only plays a role in wall patterning, hydration and stress relaxation during growth, but also may provide a driving force for cell wall expansion. In this context, pectins, the major polyanionic polysaccharides in the walls of growing cells, appear to play a critical role. Here, we will discuss (i) our current understanding of the structure–function relationship of pectins, (ii) in vivo evidence that pectin modification can drive critical phase transitions in the cell wall, (iii) how such phase transitions may drive cell wall expansion in addition to turgor pressure and (iv) the periodic cellular processes that may control phase transitions underlying cell wall assembly and expansion.</div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39244732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

High-resolution 3D mapping of rhizosphere glycan patterning using molecular probes in a transparent soil system 透明土壤系统中使用分子探针的根际聚糖图谱的高分辨率三维制图

Cell Surface Pub Date : 2021-12-01 DOI: 10.1016/j.tcsw.2021.100059

Catherine Y. Jones , Ilonka Engelhardt , Daniel Patko , Lionel Dupuy , Nicola Holden , William G.T. Willats

引用次数: 5

The biophysics of bacterial infections: Adhesion events in the light of force spectroscopy 细菌感染的生物物理学:力光谱下的粘附事件

Cell Surface Pub Date : 2021-12-01 DOI: 10.1016/j.tcsw.2021.100048

Paula Parreira , M. Cristina L. Martins

{"title":"The biophysics of bacterial infections: Adhesion events in the light of force spectroscopy","authors":"Paula Parreira , M. Cristina L. Martins","doi":"10.1016/j.tcsw.2021.100048","DOIUrl":"10.1016/j.tcsw.2021.100048","url":null,"abstract":"<div>Bacterial infections are the most eminent public health challenge of the 21st century. The primary step leading to infection is bacterial adhesion to the surface of host cells or medical devices, which is mediated by a multitude of molecular interactions. At the interface of life sciences and physics, last years advances in atomic force microscopy (AFM)-based force spectroscopy techniques have made possible to measure the forces driving bacteria-cell and bacteria-materials interactions on a single molecule/cell basis (single molecule/cell force spectroscopy).Among the bacteria-(bio)materials surface interactions, the life-threatening infections associated to medical devices involving Staphylococcus aureus and Escherichia coli are the most eminent. On the other hand, Pseudomonas aeruginosa binding to the pulmonary and urinary tract or the Helicobacter pylori binding to the gastric mucosa, are classical examples of bacteria-host cell interactions that end in serious infections.As we approach the end of the antibiotic era, acquisition of a deeper knowledge of the fundamental forces involved in bacteria – host cells/(bio)materials surface adhesion is crucial for the identification of new ligand-binding events and its assessment as novel targets for alternative anti-infective therapies.This article aims to highlight the potential of AFM-based force spectroscopy for new targeted therapies development against bacterial infections in which adhesion plays a pivotal role and does not aim to be an extensive overview on the AFM technical capabilities and theory of single molecule force spectroscopy.</div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25433430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

CreA-mediated repression of gene expression occurs at low monosaccharide levels during fungal plant biomass conversion in a time and substrate dependent manner crea介导的基因表达抑制在真菌植物生物量转化过程中以低单糖水平发生，并以时间和底物依赖的方式发生

Cell Surface Pub Date : 2021-12-01 DOI: 10.1016/j.tcsw.2021.100050

Mao Peng , Claire Khosravi , Ronnie J.M. Lubbers , Roland S. Kun , Maria Victoria Aguilar Pontes , Evy Battaglia , Cindy Chen , Sacha Dalhuijsen , Paul Daly , Anna Lipzen , Vivian Ng , Juying Yan , Mei Wang , Jaap Visser , Igor V. Grigoriev , Miia R. Mäkelä , Ronald P. de Vries

{"title":"CreA-mediated repression of gene expression occurs at low monosaccharide levels during fungal plant biomass conversion in a time and substrate dependent manner","authors":"Mao Peng , Claire Khosravi , Ronnie J.M. Lubbers , Roland S. Kun , Maria Victoria Aguilar Pontes , Evy Battaglia , Cindy Chen , Sacha Dalhuijsen , Paul Daly , Anna Lipzen , Vivian Ng , Juying Yan , Mei Wang , Jaap Visser , Igor V. Grigoriev , Miia R. Mäkelä , Ronald P. de Vries","doi":"10.1016/j.tcsw.2021.100050","DOIUrl":"10.1016/j.tcsw.2021.100050","url":null,"abstract":"<div>Carbon catabolite repression enables fungi to utilize the most favourable carbon source in the environment, and is mediated by a key regulator, CreA, in most fungi. CreA-mediated regulation has mainly been studied at high monosaccharide concentrations, an uncommon situation in most natural biotopes. In nature, many fungi rely on plant biomass as their major carbon source by producing enzymes to degrade plant cell wall polysaccharides into metabolizable sugars. To determine the role of CreA when fungi grow in more natural conditions and in particular with respect to degradation and conversion of plant cell walls, we compared transcriptomes of a creA deletion and reference strain of the ascomycete Aspergillus niger during growth on sugar beet pulp and wheat bran. Transcriptomics, extracellular sugar concentrations and growth profiling of A. niger on a variety of carbon sources, revealed that also under conditions with low concentrations of free monosaccharides, CreA has a major effect on gene expression in a strong time and substrate composition dependent manner. In addition, we compared the CreA regulon from five fungi during their growth on crude plant biomass or cellulose. It showed that CreA commonly regulated genes related to carbon metabolism, sugar transport and plant cell wall degrading enzymes across different species. We therefore conclude that CreA has a crucial role for fungi also in adapting to low sugar concentrations as occurring in their natural biotopes, which is supported by the presence of CreA orthologs in nearly all fungi.</div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25526966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Biochemical and phenotypic characterisation of the Mycobacterium smegmatis transporter UspABC 耻垢分枝杆菌转运体UspABC的生化和表型特征

Cell Surface Pub Date : 2021-12-01 DOI: 10.1016/j.tcsw.2021.100052

Magdalena Karlikowska , Albel Singh , Apoorva Bhatt , Sascha Ott , Andrew R. Bottrill , Gurdyal S. Besra , Elizabeth Fullam

{"title":"Biochemical and phenotypic characterisation of the Mycobacterium smegmatis transporter UspABC","authors":"Magdalena Karlikowska , Albel Singh , Apoorva Bhatt , Sascha Ott , Andrew R. Bottrill , Gurdyal S. Besra , Elizabeth Fullam","doi":"10.1016/j.tcsw.2021.100052","DOIUrl":"10.1016/j.tcsw.2021.100052","url":null,"abstract":"<div>Mycobacterium tuberculosis (Mtb) is an intracellular human pathogen that has evolved to survive in a nutrient limited environment within the host for decades. Accordingly, Mtb has developed strategies to acquire scarce nutrients and the mycobacterial transporter systems provide an important route for the import of key energy sources. However, the physiological role of the Mtb transporters and their substrate preference(s) are poorly characterised. Previous studies have established that the Mtb UspC solute-binding domain recognises amino- and phosphorylated-sugars, indicating that the mycobacterial UspABC transporter plays a key role in the import of peptidoglycan precursors. Herein, we have used a wide array of approaches to investigate the role of UspABC in Mycobacterium smegmatis by analysis of mutant strains that either lack the solute binding domain: ΔuspC or the entire transport complex: ΔuspABC. Analysis of mycobacterial transcripts shows that the uspABC system is functionally expressed in mycobacteria as a contiguous reading frame. Topology mapping confirms an Nin-Cin orientation of the UspAB integral membrane spanning domains. Phenotypic microarray profiling of commercially available sugars suggests, unexpectedly, that the uspC and ΔuspABC mutants had different carbon utilisation profiles and that neither strain utilised glucose-1-phosphate. Furthermore, proteomics analysis showed an alteration in the abundance of proteins involved in sugar and lipid metabolism, crucial for cell envelope synthesis, and we propose that UspABC has an important role in determining the interplay between these pathways.</div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100052"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39211482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The multi-target aspect of an MmpL3 inhibitor: The BM212 series of compounds bind EthR2, a transcriptional regulator of ethionamide activation MmpL3抑制剂的多靶点方面:BM212系列化合物结合EthR2，乙硫酰胺激活的转录调节因子

Cell Surface Pub Date : 2021-12-01 DOI: 10.1016/j.tcsw.2021.100068

Alice R. Moorey , Alejandro Cabanillas , Sarah M. Batt , Sonja Ghidelli-Disse , Beatriz Urones , Olalla Sanz , Joel Lelievre , Marcus Bantscheff , Liam R. Cox , Gurdyal S. Besra

{"title":"The multi-target aspect of an MmpL3 inhibitor: The BM212 series of compounds bind EthR2, a transcriptional regulator of ethionamide activation","authors":"Alice R. Moorey , Alejandro Cabanillas , Sarah M. Batt , Sonja Ghidelli-Disse , Beatriz Urones , Olalla Sanz , Joel Lelievre , Marcus Bantscheff , Liam R. Cox , Gurdyal S. Besra","doi":"10.1016/j.tcsw.2021.100068","DOIUrl":"10.1016/j.tcsw.2021.100068","url":null,"abstract":"<div>The emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) ensures that drug discovery efforts remain at the forefront of TB research. There are multiple different experimental approaches that can be employed in the discovery of anti-TB agents. Notably, inhibitors of MmpL3 are numerous and structurally diverse in Mtb and have been discovered through the generation of spontaneous resistant mutants and subsequent whole genome sequencing studies. However, this approach is not always reliable and can lead to incorrect target assignment and requires orthogonal confirmatory approaches. In fact, many of these inhibitors have also been shown to act as multi-target agents, with secondary targets in Mtb, as well as in other non-MmpL3-containing pathogens. Herein, we have investigated further the cellular targets of the MmpL3-inhibitor BM212 and a number of BM212 analogues. To determine the alternative targets of BM212, which may have been masked by MmpL3 mutations, we have applied a combination of chemo-proteomic profiling using bead-immobilised BM212 derivatives and protein extracts, along with whole-cell and biochemical assays. The study identified EthR2 (Rv0078) as a protein that binds BM212 analogues. We further demonstrated binding of BM212 to EthR2 through an in vitro tryptophan fluorescence assay, which showed significant quenching of tryptophan fluorescence upon addition of BM212. Our studies have demonstrated the value of revisiting drugs with ambiguous targets, such as MmpL3, in an attempt to find alternative targets and the study of off-target effects to understand more precisely target engagement of new hits emerging from drug screening campaigns.</div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39712048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Fungal cell wall components modulate our immune system 真菌细胞壁成分调节我们的免疫系统

Cell Surface Pub Date : 2021-12-01 DOI: 10.1016/j.tcsw.2021.100067

Benoit Briard , Thierry Fontaine , Thirumala-Devi Kanneganti , Neil A.R. Gow , Nicolas Papon

引用次数: 8

Prospects for anti-Candida therapy through targeting the cell wall: A mini-review 通过靶向细胞壁抗念珠菌治疗的前景:一个小综述

Cell Surface Pub Date : 2021-12-01 DOI: 10.1016/j.tcsw.2021.100063

Sanaz Ahmadipour , Robert A. Field , Gavin J. Miller

{"title":"Prospects for anti-Candida therapy through targeting the cell wall: A mini-review","authors":"Sanaz Ahmadipour , Robert A. Field , Gavin J. Miller","doi":"10.1016/j.tcsw.2021.100063","DOIUrl":"10.1016/j.tcsw.2021.100063","url":null,"abstract":"<div>The impact of fungal infections on humans is a serious public health issue that has received much less attention than bacterial infection and treatment, despite ever-increasing incidence exacerbated by an increased incidence of immunocompromised individuals in the population. Candida species, in particular, cause some of the most prevalent hospital-related fungal infections. Fungal infections are also detrimental to the well-being of grazing livestock, with milk production in dairy cows, and body and coat condition adversely affected by fungal infections. Fungal cell walls are essential for viability, morphogenesis and pathogenesis: numerous anti-fungal drugs rely on targeting either the cell wall or cell membrane, but the pipeline of available bioactives is limited. There is a clear and unmet need to identify novel targets and develop new classes of anti-fungal agents. This mini review focuses on fungal cell wall structure, composition and biosynthesis in Candida spp., including C. auris. In addition, an overview of current advances in the development of cell wall targeted therapies is considered.</div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9161033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Inactivating the mannose-ethanolamine phosphotransferase Gpi7 confers caspofungin resistance in the human fungal pathogen Candida albicans 甘露糖-乙醇胺磷酸转移酶Gpi7失活使人类真菌病原体白色念珠菌对caspofunins产生耐药性

Cell Surface Pub Date : 2021-12-01 DOI: 10.1016/j.tcsw.2021.100057

Guisheng Zeng , Xiaoli Xu , Jiaxin Gao , Alessandra da Silva Dantas , Neil A.R. Gow , Yue Wang

{"title":"Inactivating the mannose-ethanolamine phosphotransferase Gpi7 confers caspofungin resistance in the human fungal pathogen Candida albicans","authors":"Guisheng Zeng , Xiaoli Xu , Jiaxin Gao , Alessandra da Silva Dantas , Neil A.R. Gow , Yue Wang","doi":"10.1016/j.tcsw.2021.100057","DOIUrl":"10.1016/j.tcsw.2021.100057","url":null,"abstract":"<div>Understanding the molecular mechanisms governing antifungal resistance is crucial for identifying new cellular targets for developing new antifungal therapeutics. In this study, we performed a transposon-mediated genome-wide genetic screen in haploid Candida albicans to identify mutants resistant to caspofungin, the first member of the echinocandin class of antifungal drugs. A mutant exhibiting the highest resistance possessed a transposon insertion that inactivates GPI7, a gene encoding the mannose-ethanolamine phosphotransferase. Deleting GPI7 in diploid C. albicans caused similar caspofungin resistance. gpi7Δ/Δ cells showed significantly elevated cell wall chitin content and enhanced phosphorylation of Mkc1, a core component of the PKC-MAPK cell-wall integrity pathway. Deleting MKC1 suppressed the chitin elevation and caspofungin resistance of gpi7Δ/Δ cells, but overexpressing the dominant inactive form of RHO1, an upstream activator of PKC-MAPK signaling, did not. Transcriptome analysis uncovered 406 differentially expressed genes in gpi7Δ/Δ cells, many related to cell wall construction. Our results suggest that GPI7 deletion impairs cell wall integrity, which triggers the cell-wall salvage mechanism via the PKC-MAPK pathway independently of Rho1, resulting in the compensatory chitin synthesis to confer caspofungin resistance.</div>","PeriodicalId":36539,"journal":{"name":"Cell Surface","volume":"7 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tcsw.2021.100057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39181902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3