ACS Infectious Diseases最新文献_第2页

Rapid Antibiotic Susceptibility Determination by Fluorescence Lifetime Tracking of Bacterial Metabolism. 通过荧光寿命跟踪细菌新陈代谢快速确定抗生素敏感性。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-21 DOI: 10.1021/acsinfecdis.4c00491

Mauricio D Rojas-Andrade, Kumar Perinbam, Quan Thanh Nguyen, Jonathan S Kim, Francesco Palomba, Katrine Whiteson, Michelle A Digman, Albert Siryaporn, Allon I Hochbaum

{"title":"Rapid Antibiotic Susceptibility Determination by Fluorescence Lifetime Tracking of Bacterial Metabolism.","authors":"Mauricio D Rojas-Andrade, Kumar Perinbam, Quan Thanh Nguyen, Jonathan S Kim, Francesco Palomba, Katrine Whiteson, Michelle A Digman, Albert Siryaporn, Allon I Hochbaum","doi":"10.1021/acsinfecdis.4c00491","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00491","url":null,"abstract":"To combat the rise of antibiotic-resistance in bacteria and the resulting effects on healthcare worldwide, new technologies are needed that can perform rapid antibiotic susceptibility testing (AST). Conventional clinical methods for AST rely on growth-based assays, which typically require long incubation times to obtain quantitative results, representing a major bottleneck in the determination of the optimal antibiotic regimen to treat patients. Here, we demonstrate a rapid AST method based on the metabolic activity measured by fluorescence lifetime imaging microscopy (FLIM). Using lab strains and clinical isolates of Escherichia coli with tetracycline-susceptible and resistant phenotypes as models, we demonstrate that changes in metabolic state associated with antibiotic susceptibility can be quantitatively tracked by FLIM. Our results show that the magnitude of metabolic perturbation resulting from antibiotic activity correlates with susceptibility evaluated by conventional metrics. Moreover, susceptible and resistant phenotypes can be differentiated in as short as 10 min after antibiotic exposure. This FLIM-AST (FAST) method can be applied to other antibiotics and provides insights into the nature of metabolic perturbations inside bacterial cells resulting from antibiotic exposure with single cell resolution.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Past, Present, and Future of RNA Modifications in Infectious Disease Research. RNA 改造在传染病研究中的过去、现在和未来。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-21 DOI: 10.1021/acsinfecdis.4c00598

Xiaoqing Pan, Alexander Bruch, Matthew G Blango

{"title":"Past, Present, and Future of RNA Modifications in Infectious Disease Research.","authors":"Xiaoqing Pan, Alexander Bruch, Matthew G Blango","doi":"10.1021/acsinfecdis.4c00598","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00598","url":null,"abstract":"In early 2024, the National Academies of Sciences, Engineering, and Medicine (NASEM) released a roadmap for the future of research into mapping ribonucleic acid (RNA) modifications, which underscored the importance of better defining these diverse chemical changes to the RNA macromolecule. As nearly all mature RNA molecules harbor some form of modification, we must understand RNA modifications to fully appreciate the functionality of RNA. The NASEM report calls for massive mobilization of resources and investment akin to the transformative Human Genome Project of the early 1990s. Like the Human Genome Project, a concerted effort in improving our ability to assess every single modification on every single RNA molecule in an organism will change the way we approach biological questions, accelerate technological advance, and improve our understanding of the molecular world. Consequently, we are also at the start of a revolution in defining the impact of RNA modifications in the context of host-microbe and even microbe-microbe interactions. In this perspective, we briefly introduce RNA modifications to the infection biologist, highlight key aspects of the NASEM report and exciting examples of RNA modifications contributing to host and pathogen biology, and finally postulate where infectious disease research may benefit from this exciting new endeavor in globally mapping RNA modifications.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Niacin-Cholic Acid-Peptide Conjugate Act as a Potential Antibiotic Adjuvant to Mitigate Polymicrobial Infections Caused by Gram-Negative Pathogens. 烟酸-胆酸-肽共轭物是一种潜在的抗生素佐剂，可减轻由革兰氏阴性病原体引起的多微生物感染。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-20 DOI: 10.1021/acsinfecdis.4c00404

Sayed M Safwan, Devashish Mehta, Amit Arora, Steffi Khatol, Mohit Singh, Kajal Rana, Sonu K Gupta, Yashwant Kumar, Vikas Verma, Varsha Saini, Avinash Bajaj

{"title":"Niacin-Cholic Acid-Peptide Conjugate Act as a Potential Antibiotic Adjuvant to Mitigate Polymicrobial Infections Caused by Gram-Negative Pathogens.","authors":"Sayed M Safwan, Devashish Mehta, Amit Arora, Steffi Khatol, Mohit Singh, Kajal Rana, Sonu K Gupta, Yashwant Kumar, Vikas Verma, Varsha Saini, Avinash Bajaj","doi":"10.1021/acsinfecdis.4c00404","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00404","url":null,"abstract":"Polymicrobial wound infections caused by Gram-negative bacteria and associated inflammation are challenging to manage, as many antibiotics do not work against these infections. Utilizing adjuvants to repurpose the existing antibiotics for mitigating microbial infections presents an alternative therapeutic strategy. We designed and developed a niacin-cholic acid-peptide conjugate (1) to rejuvenate the therapeutic efficacy of macrolide antibiotics against Gram-negative pathogens. We conjugated niacin with anti-inflammatory properties at the carboxyl terminal of the cholic acid and dipeptide (glycine-valine) at the three hydroxyl terminals of cholic acid to obtain the amphiphile 1. Our findings demonstrated that amphiphile 1 serves as a microbial membrane disruptor that facilitates the entry of erythromycin (ERY) in bacterial cells. The combination of amphiphile 1 and ERY is bactericidal and can effectively eliminate monomicrobial and polymicrobial Gram-negative bacterial biofilms. We further demonstrated the antibacterial effectiveness of combining 1 and ERY against monomicrobial and polymicrobial wound infections. Together, these findings indicate that amphiphile 1 revitalizes the remedial efficacy of ERY against Gram-negative bacteria.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Studying Target-Engagement of Anti-Infectives by Solvent-Induced Protein Precipitation and Quantitative Mass Spectrometry. 通过溶剂诱导蛋白质沉淀和定量质谱法研究抗感染药物的靶向作用

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-20 DOI: 10.1021/acsinfecdis.4c00417

Lorenzo Bizzarri, Dominik Steinbrunn, Thibaut Quennesson, Antoine Lacour, Gabriella Ines Bianchino, Patricia Bravo, Philippe Chaignon, Jonas Lohse, Pascal Mäser, Myriam Seemann, Serge Van Calenbergh, Anna K H Hirsch, Hannes Hahne

{"title":"Studying Target-Engagement of Anti-Infectives by Solvent-Induced Protein Precipitation and Quantitative Mass Spectrometry.","authors":"Lorenzo Bizzarri, Dominik Steinbrunn, Thibaut Quennesson, Antoine Lacour, Gabriella Ines Bianchino, Patricia Bravo, Philippe Chaignon, Jonas Lohse, Pascal Mäser, Myriam Seemann, Serge Van Calenbergh, Anna K H Hirsch, Hannes Hahne","doi":"10.1021/acsinfecdis.4c00417","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00417","url":null,"abstract":"Antimicrobial resistance (AMR) poses a serious threat to global health. The rapid emergence of resistance contrasts with the slow pace of antimicrobial development, emphasizing the urgent need for innovative drug discovery approaches. This study addresses a critical bottleneck in early drug development by introducing integral solvent-induced protein precipitation (iSPP) to rapidly assess the target-engagement of lead compounds in extracts of pathogenic microorganisms under close-to-physiological conditions. iSPP measures the change in protein stability against solvent-induced precipitation in the presence of ligands. The iSPP method for bacteria builds upon established SPP procedures and features optimized denaturation gradients and minimized sample input amounts. The effectiveness of the iSPP workflow was initially demonstrated through a multidrug target-engagement study. Using quantitative mass spectrometry (LC-MS/MS), we successfully identified known drug targets of seven different antibiotics in cell extracts of four AMR-related pathogens: the three Gram-negative bacteria Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and the Gram-positive bacterium Staphylococcus aureus. The iSPP method was ultimately applied to demonstrate target-engagement of compounds derived from target-based drug discovery. We employed five small molecules targeting three enzymes in the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway─a promising focus for anti-infective drug development. The study showcases iSPP adaptability and efficiency in identifying anti-infective drug targets, advancing early-stage drug discovery against AMR.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In Vivo Activity Profiling of Biosynthetic Darobactin D22 against Critical Gram-Negative Pathogens. 生物合成 Darobactin D22 对重要革兰氏阴性病原体的体内活性分析。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-20 DOI: 10.1021/acsinfecdis.4c00687

Andreas M Kany, Franziska Fries, Carsten E Seyfert, Christoph Porten, Selina Deckarm, María Chacón Ortiz, Nelly Dubarry, Swapna Vaddi, Miriam Große, Steffen Bernecker, Birthe Sandargo, Alison V Müller, Eric Bacqué, Marc Stadler, Jennifer Herrmann, Rolf Müller

{"title":"In Vivo Activity Profiling of Biosynthetic Darobactin D22 against Critical Gram-Negative Pathogens.","authors":"Andreas M Kany, Franziska Fries, Carsten E Seyfert, Christoph Porten, Selina Deckarm, María Chacón Ortiz, Nelly Dubarry, Swapna Vaddi, Miriam Große, Steffen Bernecker, Birthe Sandargo, Alison V Müller, Eric Bacqué, Marc Stadler, Jennifer Herrmann, Rolf Müller","doi":"10.1021/acsinfecdis.4c00687","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00687","url":null,"abstract":"In recent years, naturally occurring darobactins have emerged as a promising compound class to combat infections caused by critical Gram-negative pathogens. In this study, we describe the in vivo evaluation of derivative D22, a non-natural biosynthetic darobactin analogue with significantly improved antibacterial activity. We found D22 to be active in vivo against key critical Gram-negative human pathogens, as demonstrated in murine models of Pseudomonas aeruginosa thigh infection, Escherichia coli peritonitis/sepsis, and urinary tract infection (UTI). Furthermore, we observed the restored survival of Acinetobacter baumannii-infected embryos in a zebrafish infection model. These in vivo proof-of-concept (PoC) in diverse models of infection against highly relevant pathogens, including drug-resistant isolates, highlight the versatility of darobactins in the treatment of bacterial infections and show superiority of D22 over the natural darobactin A. Together with a favorable safety profile, these findings pave the way for further optimization of the darobactin scaffold toward the development of a novel antibiotic.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accelerating Antimalarial Drug Discovery with a New High-Throughput Screen for Fast-Killing Compounds. 通过新型高通量筛选快速杀伤性化合物，加速抗疟药物的发现。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-19 DOI: 10.1021/acsinfecdis.4c00328

Takaya Sakura, Ryuta Ishii, Eri Yoshida, Kiyoshi Kita, Teruhisa Kato, Daniel Ken Inaoka

{"title":"Accelerating Antimalarial Drug Discovery with a New High-Throughput Screen for Fast-Killing Compounds.","authors":"Takaya Sakura, Ryuta Ishii, Eri Yoshida, Kiyoshi Kita, Teruhisa Kato, Daniel Ken Inaoka","doi":"10.1021/acsinfecdis.4c00328","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00328","url":null,"abstract":"The urgent need for rapidly acting compounds in the development of antimalarial drugs underscores the significance of such compounds in overcoming resistance issues and improving patient adherence to antimalarial treatments. The present study introduces a high-throughput screening (HTS) approach using 1536-well plates, employing Plasmodium falciparum lactate dehydrogenase (PfLDH) combined with nitroreductase (NTR) and fluorescent probes to evaluate inhibition of the growth of the asexual blood stage of malaria parasites. This method was adapted to efficiently assess the speed of action profiling (SAP) in a 384-well plate format, streamlining the traditionally time-consuming screening process. By successfully screening numerous compounds, this approach identified fast-killing hits early in the screening process, addressing challenges associated with artemisinin-based combination therapies. The high-throughput SAP method is expected to be of value in continuously monitoring fast-killing properties during structure-activity relationship studies, expediting the identification and development of novel, rapidly acting antimalarial drugs within phenotypic drug discovery campaigns.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repurposing Benzbromarone as an Antibacterial Agent against Gram-Positive Bacteria. 将苯溴马隆重新用作抗革兰氏阳性细菌的抗菌剂。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-19 DOI: 10.1021/acsinfecdis.4c00495

Qingyin Meng, Xueting Wang, Xuancheng Huang, Congcong Li, Zhijian Yu, Peiyu Li, Xiaoju Liu, Zewen Wen

{"title":"Repurposing Benzbromarone as an Antibacterial Agent against Gram-Positive Bacteria.","authors":"Qingyin Meng, Xueting Wang, Xuancheng Huang, Congcong Li, Zhijian Yu, Peiyu Li, Xiaoju Liu, Zewen Wen","doi":"10.1021/acsinfecdis.4c00495","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00495","url":null,"abstract":"The rise of antibiotic-resistant Gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), presents a significant challenge in clinical settings. There is a critical need for new antibacterial agents to combat these resistant strains. Our study reveals that the uricosuric drug Benzbromarone (Benz) exhibits potent antibacterial activity against Gram-positive pathogens, with minimum inhibitory concentrations (MICs) ranging from 8 to 32 μg/mL and minimum bactericidal concentrations (MBCs) ranging from 32 to 128 μg/mL against clinical isolates of S. aureus, S. epidermidis, Enterococcus faecalis, and Streptococcus agalactiae. Furthermore, Benz significantly inhibits biofilm formation at subinhibitory concentrations and eradicates mature biofilms at higher concentrations. Benz also suppresses the hemolytic activity of S. aureus, indicating its potential to reduce virulence. Proteomic and in vitro induced resistance analyses indicate that Benz inhibits protein synthesis and turnover. Additionally, Benz induces membrane depolarization and increases membrane permeability, likely by targeting the membrane phospholipid phosphatidylethanolamine (PE). In the mouse wound infection model, Benz promotes wound healing and significantly reduces bacterial load. These findings suggest that Benz is a promising candidate for developing new antibacterial therapies against Gram-positive bacterial infections.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polyamine-Enriched Exosomes from Leishmania donovani Drive Host Macrophage Polarization via Immunometabolism Reprogramming. 来自唐诺瓦利什曼原虫的富含多胺的外泌体通过免疫代谢重编程驱动宿主巨噬细胞极化

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-19 DOI: 10.1021/acsinfecdis.4c00738

Prince Sebastian, Madhulika Namdeo, Moodu Devender, Anjali Anand, Krishan Kumar, Jalaja Veronica, Radheshyam Maurya

{"title":"Polyamine-Enriched Exosomes from Leishmania donovani Drive Host Macrophage Polarization via Immunometabolism Reprogramming.","authors":"Prince Sebastian, Madhulika Namdeo, Moodu Devender, Anjali Anand, Krishan Kumar, Jalaja Veronica, Radheshyam Maurya","doi":"10.1021/acsinfecdis.4c00738","DOIUrl":"10.1021/acsinfecdis.4c00738","url":null,"abstract":"Leishmania donovani (Ld) promastigotes secrete exosomes that are crucial in host-pathogen interactions and intercellular communication by carrying parasite-specific molecules. Although the composition of cargos in Leishmania exosomes is known, the effects of the unique metabolic repertoire on immunometabolism rewiring of macrophage polarization are poorly understood. Interestingly, we found the enrichment of polyamines (PAs) such as spermidine and putrescine in the Ld-exosomes. Herein, we investigate the critical polycationic molecules and their crucial role in parasite survival. Our study shows that PA inhibition or depletion significantly impairs parasite growth and fitness, particularly in drug-resistant strains. Furthermore, we aimed to elucidate the impact of PAs-enriched Ld-exosomes on host macrophages. The data demonstrated that macrophages efficiently internalized these exosomes, leading to heightened phagocytic activity and infectivity. In addition, internalized Ld-exosomes induced M2 macrophage polarization characterized by elevated Arginase-1 expression and activity. The increased expression of the solute carrier gene (SLC3A2) and elevated intracellular spermidine levels suggest that Ld-exosomes contribute to the host PAs pool and create an anti-inflammatory milieu. These findings highlight the essential role of PAs-enriched Ld-exosomes in parasite survival and establishing a pro-parasitic environment in the host macrophage.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mycobacterium smegmatis MraZ Regulates Multiple Genes within and Outside of the dcw Operon during Hypoxia. 分枝杆菌 MraZ 在缺氧过程中调控 dcw 操作子内外的多个基因

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-18 DOI: 10.1021/acsinfecdis.4c00665

Ismail Mohamed Suleiman, Huang Yu, Junqi Xu, Junfeng Zhen, Hongxiang Xu, Abulimiti Abudukadier, Amina Rafique Hafiza, Jianping Xie

{"title":"Mycobacterium smegmatis MraZ Regulates Multiple Genes within and Outside of the dcw Operon during Hypoxia.","authors":"Ismail Mohamed Suleiman, Huang Yu, Junqi Xu, Junfeng Zhen, Hongxiang Xu, Abulimiti Abudukadier, Amina Rafique Hafiza, Jianping Xie","doi":"10.1021/acsinfecdis.4c00665","DOIUrl":"10.1021/acsinfecdis.4c00665","url":null,"abstract":"Mycobacterium tuberculosis is the most ancient human tuberculosis pathogen and has been the leading cause of death from bacterial infectious diseases throughout human history. According to the World Health Organization Global Tuberculosis Report, in 2022, 7.5 million new tuberculosis cases were identified, marking the highest number of cases since the World Health Organization initiated its worldwide tuberculosis surveillance program in 1995. The 2019 peak was 7.1 million cases, with 5.8 million cases in 2020 and 6.4 million in 2021. The increase in 2022, which may be attributed to the COVID-19 pandemic complicating tuberculosis case tracing, has raised concerns. To better understand the regulation spectrum of Mycobacterium smegmatis mraZ under hypoxia, we performed a transcriptome analysis of M. smegmatis mutant and wild-type strains using Illumina Agilent 5300 sequencing. The study identified 6898 differentially expressed genes, which were annotated with NCBI nonredundant protein sequences, a manually annotated and reviewed protein sequence database, Pfam, Clusters of Orthologous Groups of Proteins, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. Several mycobacteria transcriptional regulators, virulence genes, membrane transporters, and cell wall biosynthesis genes were annotated. These data serve as a valuable resource for future investigations and may offer insight into the development of drugs to combat M. tuberculosis infection.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Performance Assessment of ELISA Using the Trypanosoma cruzi-Specific Antigen Tc323 for the Diagnosis of Chronic Chagas Disease. 使用克氏锥虫特异性抗原 Tc323 进行 ELISA 诊断慢性南美锥虫病的性能评估

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-16 DOI: 10.1021/acsinfecdis.4c00784

Micaela Soledad Ossowski, Juan Pablo Gallardo, Raul Chadi, Yolanda Hernández, Marisa Fernández, Jorge Diego Marco, Omar Triana-Chavez, Melissa S Nolan, Angelica Pech May, Janine M Ramsey, Juan C Villar, Fernán Agüero, Mariana Potenza, Karina Andrea Gómez

{"title":"Performance Assessment of ELISA Using the Trypanosoma cruzi-Specific Antigen Tc323 for the Diagnosis of Chronic Chagas Disease.","authors":"Micaela Soledad Ossowski, Juan Pablo Gallardo, Raul Chadi, Yolanda Hernández, Marisa Fernández, Jorge Diego Marco, Omar Triana-Chavez, Melissa S Nolan, Angelica Pech May, Janine M Ramsey, Juan C Villar, Fernán Agüero, Mariana Potenza, Karina Andrea Gómez","doi":"10.1021/acsinfecdis.4c00784","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00784","url":null,"abstract":"In the chronic phase of Chagas disease (CCD), diagnosis relies on detecting specific IgG antibodies due to the low or absent presence of the parasiteTrypanosoma cruzi in human blood. However, the performance of current serological tests is highly variable, lacking a \"gold standard\" assay with 100% sensitivity and specificity, which challenges the exploration of new biomarkers. In the present study, we evaluated the diagnostic accuracy of an optimized ELISA using the predicted immunogenic domains (called TcD3 and TcD6) of Tc323, a protein highly conserved among T. cruzi strains but absent in other clinically significant parasites such as Leishmania spp. This study was conducted using plasma or serum samples from CCD individuals with different clinical manifestations and living in endemic regions in Latin America, subjects with unrelated infectious diseases, and noninfected donors. The sensitivity and specificity of recombinant TcD3 were 90.8% and 92.6%, respectively, while rTcD6 displayed values of 93.1% and 93.6% for the same parameters. Area under curve (AUC) values were 0.949 for rTcD3 and 0.954 for rTcD6. The receiver operative characteristic (ROC) curve showed a highly significant difference between CCD individuals and noninfected donors. Cross-reactivity was 10.2% for rTcD3 and 8.2% for rTcD6 in subjects infected with leishmaniasis or with toxoplasmosis. In addition, the reactivity against rTcD3 differed among some geographical areas while no significant difference was found using both domains for the detection of T. cruzi-infected individuals with or without cardiac symptoms. Our findings show that the recombinant antigens rTcD3 and rTcD6 could be used as highly potential biomarkers for the serological diagnosis of CCD.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0