iSciencePub Date : 2024-11-06DOI: 10.1016/j.isci.2024.111332
Kathrine Nygaard Borg , Ayush Shetty , Guangyao Cheng , Shaodi Zhu , Tianle Wang , Wu Yuan , Ho Pui Ho , Birgitta Ruth Knudsen , Cinzia Tesauro , Yi-Ping Ho
{"title":"Hydrogel bead-based isothermal detection (BEAD-ID) for assessing the activity of DNA-modifying enzymes","authors":"Kathrine Nygaard Borg , Ayush Shetty , Guangyao Cheng , Shaodi Zhu , Tianle Wang , Wu Yuan , Ho Pui Ho , Birgitta Ruth Knudsen , Cinzia Tesauro , Yi-Ping Ho","doi":"10.1016/j.isci.2024.111332","DOIUrl":"10.1016/j.isci.2024.111332","url":null,"abstract":"<div><div>DNA-modifying enzymes are crucial in biological processes and have significant clinical implications. Traditional quantification methods often overlook enzymatic activity, the true determinants of enzymes’ functions. We present hydrogel Bead-based Isothermal Detection (BEAD-ID), utilizing uniform hydrogel bead-based microreactors to evaluate DNA-modifying enzyme activity on-bead. We fabricated homogeneous oligo-conjugated polyacrylamide (oligo-PAA) beads <em>via</em> droplet microfluidics, optimized for capturing and amplifying enzyme-modified nanosensors. By incorporating DNA oligos within the hydrogel network, BEAD-ID retains isothermally amplified products, facilitating <em>in situ</em> detection of enzyme activities on-bead. We validate BEAD-ID by quantifying human topoisomerase I (TOP1) and restriction endonuclease EcoRI, showing a direct correlation between enzyme concentration and fluorescence intensity, demonstrating the platform’s sensitivity (6.25 nM TOP1, 6.25 U/μL EcoRI) and reliability in food matrix (25 U/μL EcoRI). Additionally, a customized flow cytometry-mimicking setup allows high-throughput detection at 352 Hz with objective assessment. BEAD-ID, offering flexibility and scalability, is a promising tool for studying DNA-modifying enzymes.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111332"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2024-11-06DOI: 10.1016/j.isci.2024.111330
Deming Zhang , Wenjian Wang , Chunli Song , Tingting Huang , Hongyu Chen , Zihao Liu , Yiwen Zhou , Heping Wang
{"title":"Comparative genomic study of non-typeable Haemophilus influenzae in children with pneumonia and healthy controls","authors":"Deming Zhang , Wenjian Wang , Chunli Song , Tingting Huang , Hongyu Chen , Zihao Liu , Yiwen Zhou , Heping Wang","doi":"10.1016/j.isci.2024.111330","DOIUrl":"10.1016/j.isci.2024.111330","url":null,"abstract":"<div><div>Non-typeable <em>Haemophilus influenzae</em> (NTHi) is a common pathogen causing respiratory infections, including pneumonia in children, and can also be found in the upper respiratory tracts of asymptomatic individuals. This study examines genomic variations between NTHi strains from healthy children and those from children with acute or chronic community-acquired pneumonia (CAP). Using bacterial genome-wide association studies (bGWAS), we compared these strains to identify key differences. Our analysis revealed that approximately 32% of genes exhibit variations between commensal and pathogenic states. Notably, we identified changes in <em>peptidoglycan biosynthesis</em> pathways and significant virulence factors associated with pneumonia. Furthermore, we observed a significant difference in β-lactam resistance due to PBP3 mutations between the healthy and pneumonia groups, confirmed by the ampicillin susceptibility test and characterized by the mutation pattern D350N, S357N, S385T, L389F. These findings contribute valuable insights into the genomic basis of NTHi pathogenicity and may inform more targeted clinical diagnostics and treatments.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111330"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2024-11-06DOI: 10.1016/j.isci.2024.111336
Israel Pérez-Chávez , John N. Koberstein , Julia Malo Pueyo , Eduardo H. Gilglioni , Didier Vertommen , Nicolas Baeyens , Daria Ezeriņa , Esteban N. Gurzov , Joris Messens
{"title":"Tracking fructose 1,6-bisphosphate dynamics in liver cancer cells using a fluorescent biosensor","authors":"Israel Pérez-Chávez , John N. Koberstein , Julia Malo Pueyo , Eduardo H. Gilglioni , Didier Vertommen , Nicolas Baeyens , Daria Ezeriņa , Esteban N. Gurzov , Joris Messens","doi":"10.1016/j.isci.2024.111336","DOIUrl":"10.1016/j.isci.2024.111336","url":null,"abstract":"<div><div>HYlight is a genetically encoded fluorescent biosensor that ratiometrically monitors fructose 1,6-bisphosphate (FBP), a key glycolytic metabolite. Given the role of glucose in liver cancer metabolism, we expressed HYlight in human liver cancer cells and primary mouse hepatocytes. Through <em>in vitro</em>, <em>in silico</em>, and <em>in cellulo</em> experiments, we showed HYlight’s ability to monitor FBP changes linked to glycolysis, not gluconeogenesis. HYlight’s affinity for FBP was ∼1 μM and stable within physiological pH range. HYlight demonstrated weak binding to dihydroxyacetone phosphate, and its ratiometric response was influenced by both ionic strength and phosphate. Therefore, simulating cytosolic conditions <em>in vitro</em> was necessary to establish a reliable correlation between HYlight’s cellular responses and FBP concentrations. FBP concentrations were found to be in the lower micromolar range, far lower than previous millimolar estimates. Altogether, this biosensor approach offers real-time monitoring of FBP concentrations at single-cell resolution, making it an invaluable tool for the understanding of cancer metabolism.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111336"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2024-11-06DOI: 10.1016/j.isci.2024.111339
Ana Rotter , Despoina Varamogianni-Mamatsi , Alenka Zvonar Pobirk , Mirjam Gosenca Matjaž , Mercedes Cueto , Ana R. Díaz-Marrero , Rósa Jónsdóttir , Kolbrún Sveinsdóttir , Teresa S. Catalá , Giovanna Romano , Bahar Aslanbay Guler , Eylem Atak , Maja Berden Zrimec , Daniel Bosch , Irem Deniz , Susana P. Gaudêncio , Ernesta Grigalionyte-Bembič , Katja Klun , Luen Zidar , Anna Coll Rius , Manolis Mandalakis
{"title":"Marine cosmetics and the blue bioeconomy: From sourcing to success stories","authors":"Ana Rotter , Despoina Varamogianni-Mamatsi , Alenka Zvonar Pobirk , Mirjam Gosenca Matjaž , Mercedes Cueto , Ana R. Díaz-Marrero , Rósa Jónsdóttir , Kolbrún Sveinsdóttir , Teresa S. Catalá , Giovanna Romano , Bahar Aslanbay Guler , Eylem Atak , Maja Berden Zrimec , Daniel Bosch , Irem Deniz , Susana P. Gaudêncio , Ernesta Grigalionyte-Bembič , Katja Klun , Luen Zidar , Anna Coll Rius , Manolis Mandalakis","doi":"10.1016/j.isci.2024.111339","DOIUrl":"10.1016/j.isci.2024.111339","url":null,"abstract":"<div><div>As the global population continues to grow, so does the demand for longer, healthier lives and environmentally responsible choices. Consumers are increasingly drawn to naturally sourced products with proven health and wellbeing benefits. The marine environment presents a promising yet underexplored resource for the cosmetics industry, offering bioactive compounds with the potential for safe and biocompatible ingredients. This manuscript provides a comprehensive overview of the potential of marine organisms for cosmetics production, highlighting marine-derived compounds and their applications in skin/hair/oral-care products, cosmeceuticals and more. It also lays down critical safety considerations and addresses the methodologies for sourcing marine compounds, including harvesting, the biorefinery concept, use of systems biology for enhanced product development, and the relevant regulatory landscape. The review is enriched by three case studies: design of macroalgal skincare products in Iceland, establishment of a microalgal cosmetics spin-off in Italy, and the utilization of marine proteins for cosmeceutical applications.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111339"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2024-11-06DOI: 10.1016/j.isci.2024.111335
Vishal Midya , Kiran Nagdeo , Jamil M. Lane , Libni A. Torres-Olascoaga , Gabriela Gil Martínez , Megan K. Horton , Nia McRae , Inessa Lopez , Julio Landero , Chris Gennings , Martha Maria Téllez-Rojo , Robert O. Wright , Manish Arora , Shoshannah Eggers
{"title":"Akkermansia muciniphila attenuates association between specific metal exposures during pregnancy and depressive symptoms in late childhood","authors":"Vishal Midya , Kiran Nagdeo , Jamil M. Lane , Libni A. Torres-Olascoaga , Gabriela Gil Martínez , Megan K. Horton , Nia McRae , Inessa Lopez , Julio Landero , Chris Gennings , Martha Maria Téllez-Rojo , Robert O. Wright , Manish Arora , Shoshannah Eggers","doi":"10.1016/j.isci.2024.111335","DOIUrl":"10.1016/j.isci.2024.111335","url":null,"abstract":"<div><div>Emerging research suggests that exposures to metals during pregnancy and consequent disruptions in gut microbiome (GM) are associated with depressive disorders in childhood. <em>Akkermansia muciniphila</em>, a GM bacteria, has been studied for its potential antidepressant effects. However, its role in influencing the association between prenatal metal exposures and depressive symptoms during childhood is unknown. Leveraging a well-characterized pediatric birth cohort and its microbiome substudy (<em>n</em> = 112), we investigated whether a certain subgroup of children at 9-11-year-of-age (characterized by a specific pattern of prenatal exposure to groups of metals or metal-clique) had worsened depressive symptoms and if the presence of <em>A.muciniphila</em> in GM modifies this association. A subgroup of children characterized by the prenatal metal-clique signature of zinc-chromium-cobalt had significantly increased depression scores; however, within that subgroup, children with <em>A.muciniphila</em> had much lower depression scores than those without <em>A.muciniphila</em> in the GM. Our analysis provides exploratory evidence hypothesizing <em>A.muciniphila</em> as an intervention attenuating the effect of prenatal metal-exposures-associated depressive disorders in late childhood.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111335"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2024-11-06DOI: 10.1016/j.isci.2024.111327
Kaiyun Y. Gou , Yanran R. Li , Honglin L. Song , Rong Lu , Jie Jiang
{"title":"Optimization strategy of the emerging memristors: From material preparation to device applications","authors":"Kaiyun Y. Gou , Yanran R. Li , Honglin L. Song , Rong Lu , Jie Jiang","doi":"10.1016/j.isci.2024.111327","DOIUrl":"10.1016/j.isci.2024.111327","url":null,"abstract":"<div><div>With the advent of the post-Moore era and the era of big data, advanced data storage and processing technology are in urgent demand to break the von Neumann bottleneck. Neuromorphic computing, which mimics the computational paradigms of the human brain, offers an efficient and energy-saving way to process large datasets in parallel. Memristor is an ideal architectural unit for constructing neuromorphic computing. It offers several advantages, including a simple structure, low power consumption, non-volatility, and easy large-scale integration. The hardware-based neural network using a large-scale cross array of memristors is considered to be a potential scheme for realizing the next-generation neuromorphic computing. The performance of these devices is a key to constructing the expansive memristor arrays. Herein, this paper provides a comprehensive review of current strategies for enhancing the performance of memristors, focusing on the electronic materials and device structures. Firstly, it examines current device fabrication techniques. Subsequently, it deeply analyzes methods to improve both the performance of individual memristor and the overall performance of device array from a material and structural perspectives. Finally, it summarizes the applications and prospects of memristors in neuromorphic computing and multimodal sensing. It aims at providing an insightful guide for developing the brain-like high computer chip.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111327"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2024-11-06DOI: 10.1016/j.isci.2024.111333
Nursen Balekoglu , Jean-Francois Michaud , Rachelle Sauvé , Kehinde S. Ayinde , Sichun Lin , Yijun Liu , Daniel A. Kramer , Kaiyue Zhang , Anika Steffen , Theresia Stradal , Stephane Angers , Baoyu Chen , Patricia T. Yam , Frédéric Charron
{"title":"The WAVE regulatory complex interacts with Boc and is required for Shh-mediated axon guidance","authors":"Nursen Balekoglu , Jean-Francois Michaud , Rachelle Sauvé , Kehinde S. Ayinde , Sichun Lin , Yijun Liu , Daniel A. Kramer , Kaiyue Zhang , Anika Steffen , Theresia Stradal , Stephane Angers , Baoyu Chen , Patricia T. Yam , Frédéric Charron","doi":"10.1016/j.isci.2024.111333","DOIUrl":"10.1016/j.isci.2024.111333","url":null,"abstract":"<div><div>During development, Shh attracts axons of spinal cord commissural neurons to the floor plate. Shh-mediated attraction of commissural axons requires the receptor Boc. How Boc regulates cytoskeletal changes in growth cones in response to Shh is not fully understood. To identify effectors of Boc in Shh-mediated axon guidance, we used BioID to screen for proteins in proximity to Boc. Top hits included members of the WAVE regulatory complex (WRC), which acts downstream of Rac1 to promote actin cytoskeleton assembly. Therefore, we hypothesized that the WRC is important for Shh-mediated growth cone turning. Using biochemical and cellular assays, we found that Boc directly interacts with the WRC and that this interaction can occur in live cells. Moreover, we found that knockdown of <em>Nckap1</em> and <em>Cyfip1/2,</em> two subunits of the WRC, in commissural neurons, impairs axon attraction toward a Shh gradient. Our results demonstrate that the WRC is required for Shh-mediated axon attraction.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111333"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2024-11-06DOI: 10.1016/j.isci.2024.111337
Isabella C. Galvão , Manuela Lemoine , Lauana A. Messias , Patrícia A.O.R.A. Araújo , Jaqueline C. Geraldis , Clarissa L. Yasuda , Marina K.M. Alvim , Enrico Ghizoni , Helder Tedeschi , Fernando Cendes , Fabio Rogerio , Iscia Lopes-Cendes , Diogo F.T. Veiga
{"title":"Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia","authors":"Isabella C. Galvão , Manuela Lemoine , Lauana A. Messias , Patrícia A.O.R.A. Araújo , Jaqueline C. Geraldis , Clarissa L. Yasuda , Marina K.M. Alvim , Enrico Ghizoni , Helder Tedeschi , Fernando Cendes , Fabio Rogerio , Iscia Lopes-Cendes , Diogo F.T. Veiga","doi":"10.1016/j.isci.2024.111337","DOIUrl":"10.1016/j.isci.2024.111337","url":null,"abstract":"<div><div>Focal cortical dysplasia (FCD) is a neurodevelopmental condition characterized by malformations of the cerebral cortex that often cause drug-resistant epilepsy. In this study, we performed multi-omics single-nuclei profiling to map the chromatin accessibility and transcriptome landscapes of FCD type II, generating a comprehensive multimodal single-nuclei dataset comprising 61,525 cells from 11 clinical samples of lesions and controls. Our findings revealed profound chromatin, transcriptomic, and cellular alterations affecting neuronal and glial cells in FCD lesions, including the selective loss of upper-layer excitatory neurons, significant expansion of oligodendrocytes and immature astrocytic populations, and a distinct neuronal subpopulation harboring dysmorphic neurons. Furthermore, we uncovered activated microglia subsets, particularly in FCD IIb cases. This comprehensive study unveils neuronal and glial cell states driving FCD development and epileptogenicity, enhancing our understanding of FCD and offering directions for targeted therapy development.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111337"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2024-11-05DOI: 10.1016/j.isci.2024.111321
Simone Romeni , Daniela De Luca , Luca Pierantoni , Laura Toni , Gabriele Marino , Sara Moccia , Silvestro Micera
{"title":"A computational model to design wide field-of-view optic nerve neuroprostheses","authors":"Simone Romeni , Daniela De Luca , Luca Pierantoni , Laura Toni , Gabriele Marino , Sara Moccia , Silvestro Micera","doi":"10.1016/j.isci.2024.111321","DOIUrl":"10.1016/j.isci.2024.111321","url":null,"abstract":"<div><div>Retinal stimulation (RS) allows restoring vision in blind patients, but it covers only a narrow region of the visual field. Optic nerve stimulation (ONS) has the potential to produce visual perceptions spanning the whole visual field, but it produces very irregular phosphenes. We introduced a geometrical model converting retinal and optic nerve firing rates into visual perceptions and vice versa and a method to estimate the best perceptions elicitable through an electrode configuration. We then compared in silico ONS and RS through simulated prosthetic vision of static and dynamic visual scenes. Both simulations and SPV experiments showed that it might be possible to reconstruct natural visual scenes with ONS and RS, and that ONS wide field-of-view allows the perception of more detail in dynamic scenarios than RS. Our findings suggest that ONS could represent an interesting approach for vision restoration and that our model can be used to optimize it.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111321"},"PeriodicalIF":4.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2024-11-05DOI: 10.1016/j.isci.2024.111319
Elizaveta V. Starikova , Yulia S. Galeeva , Dmitry E. Fedorov , Elena V. Korneenko , Anna S. Speranskaya , Oksana V. Selezneva , Polina Y. Zoruk , Ksenia M. Klimina , Vladimir A. Veselovsky , Maxim D. Morozov , Daria I. Boldyreva , Evgenii I. Olekhnovich , Alexander I. Manolov , Alexander V. Pavlenko , Ivan E. Kozlov , Oleg O. Yanushevich , Natella I. Krikheli , Oleg V. Levchenko , Dmitry N. Andreev , Filipp S. Sokolov , Elena N. Ilina
{"title":"Oropharyngeal resistome remains stable during COVID-19 therapy, while fecal resistome shifts toward a less diverse resistotype","authors":"Elizaveta V. Starikova , Yulia S. Galeeva , Dmitry E. Fedorov , Elena V. Korneenko , Anna S. Speranskaya , Oksana V. Selezneva , Polina Y. Zoruk , Ksenia M. Klimina , Vladimir A. Veselovsky , Maxim D. Morozov , Daria I. Boldyreva , Evgenii I. Olekhnovich , Alexander I. Manolov , Alexander V. Pavlenko , Ivan E. Kozlov , Oleg O. Yanushevich , Natella I. Krikheli , Oleg V. Levchenko , Dmitry N. Andreev , Filipp S. Sokolov , Elena N. Ilina","doi":"10.1016/j.isci.2024.111319","DOIUrl":"10.1016/j.isci.2024.111319","url":null,"abstract":"<div><div>Antimicrobial resistance poses a serious threat to global public health. The COVID-19 pandemic underscored the need to monitor the dissemination of antimicrobial resistance genes and understand the mechanisms driving this process. In this study, we analyzed changes to the oropharyngeal and fecal resistomes of patients with COVID-19 undergoing therapy in a hospital setting. A targeted sequencing panel of 4,937 resistance genes was used to comprehensively characterize resistomes. Our results demonstrated that the oropharyngeal resistome is homogeneous, showing low variability over time. In contrast, fecal samples clustered into two distinct resistotypes that were only partially related to enterotypes. Approximately half of the patients changed their resistotype within a week of therapy, with the majority transitioning to a less diverse and <em>ermB</em>-dominated resistotype 2. Common macrolide resistance genes were identified in over 80% of both oropharyngeal and fecal samples, likely originating from streptococci. Our findings suggest that the fecal resistome is a dynamic system that can exist in certain “states” and is capable of transitioning from one state to another. To date, this is the first study to comprehensively describe the oropharyngeal resistome and its variability over time, and one of the first studies to demonstrate the temporal dynamics of the fecal resistotypes.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111319"},"PeriodicalIF":4.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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