ACS Infectious Diseases最新文献

{"title":"Targeting G-Quadruplex with Bis-thiourea Compounds Inhibits SARS-CoV-2 Replication","authors":"Shogo Sasaki,&nbsp;Shogo Nakajima,&nbsp;Rena Nohara,&nbsp;Hiroyuki Endo,&nbsp;Norito Takeuchi,&nbsp;Taiji Oyama,&nbsp;Naoya Iwano,&nbsp;Kaori Tsukakoshi,&nbsp;Kazunori Ikebukuro,&nbsp;Akira Shiraishi,&nbsp;Kazuo Nagasawa,&nbsp;Koichi Watashi* and Masayuki Tera*,&nbsp;","doi":"10.1021/acsinfecdis.5c00095","DOIUrl":"10.1021/acsinfecdis.5c00095","url":null,"abstract":"<p >Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus behind COVID-19, has a single-stranded RNA genome approximately 30 kb long. Due to its continuous mutation and potential for reemergence, identifying new therapeutic targets is crucial. G-quadruplexes (G4s), high-order genome structures, are promising therapeutic targets for various viral diseases due to their ability to inhibit virus replication. To develop new anti-SARS-CoV-2 drugs targeting G4s, identifying G4 structures in the viral genome and finding small molecules that selectively bind to them is essential. Recently, we identified a unique G4-forming sequence (SC-2) in SARS-CoV-2 RNA using our developed G4 prediction tool. We screened our in-house compound library with a Thiazole Orange (TO) displacement assay and found bis-urea/bis-thiourea compounds that bind to the SC-2 G4 motif. Notably, a bis-thiourea compound (BT1) inhibited SARS-CoV-2 replication in a VeroE6/TMPRSS2 infection assay, showing antiviral activity comparable to remdesivir. The displacement efficacy of TO from G4 by synthesized bis-urea/bis-thiourea derivatives to SC-2 G4 correlated strongly with reduced viral RNA levels in infected cells. Fluorescently labeled bis-thiourea compounds accumulated near double-stranded RNA during viral replication, highlighting their potential to target viral RNA G4s. Our study offers a new approach for anti-SARS-CoV-2 drug development.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"11 8","pages":"2131–2144"},"PeriodicalIF":3.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657838","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}

{"title":"Smart Wound Dressing with Real-Time Colorimetric Detection of Antimicrobial Resistance and Infection","authors":"Vaishnavi N,&nbsp;Ramakrishnan Ganesan* and Jayati Ray Dutta*,&nbsp;","doi":"10.1021/acsinfecdis.5c00256","DOIUrl":"10.1021/acsinfecdis.5c00256","url":null,"abstract":"<p >The increasing prevalence of wound infections and antimicrobial resistance (AMR) highlights the urgent need for advanced solutions that go beyond traditional antibiotic therapies, which could combine innovative treatment with diagnostic tools. This study presents a multifunctional smart wound dressing, integrating an antimicrobial wound-contacting layer with a chromogenic hydrogel system for real-time detection of infections and AMR. The dressing consists of electrospun poly(ε-caprolactone) (PCL) fibers functionalized with ionic silver anchored to quaternary ammonium moieties, offering potent antibacterial activity. It is coupled with two chromogenic substrates, targeting crucial intracellular enzymes: (i) chlorophenol red-β-<span>d</span>-galactopyranoside (CPRG) for β-galactosidase-based rapid colorimetric detection of pathogenic infections and (ii) nitrocefin for identifying β-lactamase-mediated AMR. Extensive <i>in vitro</i> and <i>ex vivo</i> studies with these chromogens show rapid color-change responses and precise AMR identification. The direct colorimetric method eliminates the need for sophisticated equipment, trained personnel, or lengthy laboratory analyses. Additionally, the results are integrated with the Internet of Things (IoT), which decodes the color changes, enabling the healthcare providers to access the real-time infection status. This innovative dressing aids timely interventions, reduces reliance on traditional antibiotics, and addresses AMR challenges, making it highly suitable for point-of-care (POC) applications, including in resource-limited settings.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"11 8","pages":"2218–2231"},"PeriodicalIF":3.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657837","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}

{"title":"Pse-T2-Based Short Peptides with Broad-Spectrum Antimicrobial Activity, Stability, and Safety Combat MDR <i>Staphylococcus aureus In Vitro</i> and in Mouse Infection Model.","authors":"Hee Kyoung Kang, Yoonkyung Park","doi":"10.1021/acsinfecdis.4c01034","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c01034","url":null,"abstract":"<p><p>Infections caused by MDR pathogens are on the rise worldwide, and relying on conventional antibiotics can be life-threatening for patients. To address this issue, we used a functional truncated peptide, Pse-T2-C12, which exhibited excellent antibacterial, antibiofilm, and antipersister activities, along with a rapid killing rate against all tested pathogens. Pse-T2-C12 kills bacterial cells via pore formation, permeabilization, and disruption of bacterial membranes. Pse-T2-C12 did not induce resistance development, remained stable over pH, temperature, and serum conditions, and showed no detectable toxicity <i>in vitro</i> and <i>in vivo</i>. Moreover, <i>in vivo</i> data showed that Pse-T2-C12 reduced MDR <i>Staphylococcus aureus</i> infection, resulting in a reduced inflammatory response, decreased coagulation, and pain reduction. These findings highlight Pse-T2-C12 as a promising antibiotic candidate owing to its easy synthesis, economic benefits, and ability to treat MDR bacterial infections.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657836","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}

{"title":"Vancomycin Sensitization in Pseudomonas aeruginosa is Contingent on Limited Metabolic Flux","authors":"Martina M. Golden,&nbsp;Shehreen Siddiqui,&nbsp;Vivian Ohanaja,&nbsp;Savannah J. Post and William M. Wuest*,&nbsp;","doi":"10.1021/acsinfecdis.5c00225","DOIUrl":"10.1021/acsinfecdis.5c00225","url":null,"abstract":"<p >The global antibiotic resistance crisis causes nearly 5 million deaths annually. <i>Pseudomonas aeruginosa</i>, a virulent Gram-negative bacterium, is a major cause of hospital-acquired infections, often coexisting with<i>Staphylococcus aureus</i>. Previous studies showed <i>P. aeruginosa</i> can be sensitized to vancomycin through altered nutrient availability. This study explores the scope and mechanisms of this phenomenon using a dual-pronged approach focused on primary metabolism. Through the application of a tool compound that targets succinate dehydrogenase, we sought to correlate this sensitization to effects seen in minimal media growth. Carbon supplementation can partially restore tolerance with sources that aid in detecting environmental changes, low iron levels, and altered metabolism. Vancomycin sensitization was also observed in multidrug-resistant clinical isolates, indicating that compensatory mutations may influence antibiotic susceptibility and metabolic flux. Our findings show that <i>P. aeruginosa</i> can also be sensitized to other gram-positive-specific antibiotics, such as erythromycin, chloramphenicol, and amoxicillin, with no apparent correlation to the antibiotic’s size or mechanism. These findings highlight how different growth conditions affect the susceptibility of <i>P. aeruginosa</i> to clinically relevant antibiotics.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"11 8","pages":"2169–2177"},"PeriodicalIF":3.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsinfecdis.5c00225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Testing of Blood Samples to Diagnose Bloodstream Infections","authors":"Xiaoyi Yang,&nbsp;Yiyang Fan,&nbsp;Xin Xu,&nbsp;Tong Shen,&nbsp;Xiaohui An,&nbsp;Yuting Zhang,&nbsp;Ze Zhang,&nbsp;Hongzhi Pan* and Dong Chang*,&nbsp;","doi":"10.1021/acsinfecdis.5c00109","DOIUrl":"10.1021/acsinfecdis.5c00109","url":null,"abstract":"<p >Bloodstream infection (BSI) is a critical condition with extremely high mortality. Rapid and accurate diagnosis is crucial for effective treatment. The traditional blood culture (BC) method has issues, such as long testing times and limited sensitivity, making it challenging to meet the need for timely diagnosis. To address this problem, various molecular biology methods for directly detecting blood samples (whole blood, plasma, serum, and positive BC samples) have emerged. These include Raman spectroscopy, mass spectrometry, nucleic acid amplification, and hybridization techniques (such as the CRISPR/Cas system, digital droplet PCR (ddPCR), and T2 magnetic resonance (T2MR)), biosensors, and next-generation sequencing (NGS). These methods can quickly identify pathogens and their drug-resistant markers, significantly reducing diagnostic delays and helping to provide earlier targeted treatment. This article systematically analyzes the principles, advantages, and disadvantages of these advanced techniques, explores their value in revolutionizing the BSI diagnostic model, and looks ahead to future development directions, providing a reference for research and clinical applications in this field.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"11 8","pages":"2051–2067"},"PeriodicalIF":3.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641184","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}

{"title":"A Strain-Specific Clumping Mechanism Enables Staphylococcus aureus ST88 to Circumvent the Host Neutrophil Response","authors":"Vandanashree Muralidharan,&nbsp;Rakesh Kumar Pradhan,&nbsp;Savitha Nadig,&nbsp;Anitha N Bavikatte,&nbsp;Sneha Murthy,&nbsp;Mitali Shah,&nbsp;Shruthi Sridhar Vembar,&nbsp;Siddharth Jhunjhunwala and Balasubramanian Gopal*,&nbsp;","doi":"10.1021/acsinfecdis.4c01009","DOIUrl":"10.1021/acsinfecdis.4c01009","url":null,"abstract":"<p >Community-associated methicillin-resistant <i>Staphylococcus aureus</i> strains often demonstrate enhanced virulence, with different strains eliciting varied immune responses in humans. The factors that enable some <i>S. aureus</i> strains to evade killing by immune cells remain unclear. Here, we describe studies designed to understand <i>ex vivo</i> intracellular survival assays that revealed that while a well-characterized MRSA ST8 strain (USA300) was susceptible to phagocytic clearance, a genotypically similar MRSA ST88 strain (LVP-7) effectively evaded neutrophil killing. A pronounced enhancement in neutrophil lysis upon ST88 infection suggests that ST88 can infect polymorphonuclear human neutrophils yet circumvent phagocytosis-associated killing. Both ST8 and ST88 strains show a similar response to extracellular stress elicited by H₂O₂, HOCl, or NO. Host bactericidal mechanisms, such as the release of reactive oxygen species, myeloperoxidases, and elastases, were similar when infected with either strain. The transcriptome profile of ST88 upon phagocytosis at different stages of infection alongside a comparison of the phenotypic traits of ST8 and ST88 revealed factors that could potentially rationalize ST88’s evasion of killing by neutrophils. Upon phagocytosis, the ST88 transcriptome showed distinct changes in the levels of the quorum sensing accessory gene regulator (Agr). Confocal imaging revealed that the ST88 strain clusters more with higher bacteria per infected neutrophil than the ST8 strain. A pronounced reduction in ST88 clumping was seen upon the addition of the cognate autoinducing peptide AIP-III, consistent with the premise that the Agr mechanism plays a role in the evasion of neutrophil-mediated killing by the ST88 strain. It thus appears likely that clumping, modulated by quorum sensing, provides a route for this <i>S. aureus</i> strain to evade the human innate immune response.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"11 8","pages":"2068–2079"},"PeriodicalIF":3.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641182","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}

{"title":"AI Drug Discovery: Expanding the Horizons of Infectious Disease Therapeutics","authors":"Marta Bon,&nbsp;Fraser Cunningham,&nbsp;Jyoti Chauhan,&nbsp;Brian Lu,&nbsp;Sid Jain,&nbsp;Brandon Probst,&nbsp;Ian Goodfellow* and Alberto Bresciani*,&nbsp;","doi":"10.1021/acsinfecdis.5c00462","DOIUrl":"10.1021/acsinfecdis.5c00462","url":null,"abstract":"<p >Drug discovery and development for infectious diseases has transformed from phenotypic screening to rational design, and now embracing artificial intelligence (AI) to accelerate and optimize therapeutic development. We describe our use of AI to analyze vast and diverse data sets to generate therapeutic hypotheses and identify novel drug targets. We discuss generative design, active learning and automation. Finally we cover the use of AI in development. We believe that decoding biology and industrializing discovery through AI and automation is revolutionizing drug discovery in general, and has the potential to deliver improved patient outcomes and global health benefits in infectious diseases.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"11 8","pages":"2048–2050"},"PeriodicalIF":3.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641183","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}

{"title":"Extracellular vesicles from Distinct Histoplasma capsulatum Strains Modulate Phagocyte Function and Promote Fungal Persistence","authors":"Taiane N. Souza,&nbsp;Alessandro F. Valdez,&nbsp;Ana Claudia G. Zimbres,&nbsp;Bianca A. G. Sena,&nbsp;Flavia C. G. Reis,&nbsp;Marcio L. Rodrigues,&nbsp;Daniel Zamith-Miranda,&nbsp;Allan J. Guimarães,&nbsp;Alessandra A. Filardy,&nbsp;Joshua D. Nosanchuk and Leonardo Nimrichter*,&nbsp;","doi":"10.1021/acsinfecdis.5c00378","DOIUrl":"10.1021/acsinfecdis.5c00378","url":null,"abstract":"<p >Fungal extracellular vesicles (EVs) are lipid-bilayer compartments that transport a wide range of molecules, including proteins, polysaccharides, pigments, small metabolites, lipids, and RNA. In fungal pathogens, EVs harbor virulence factors as well as antigenic determinants that modulate the host immune response. In this work, we investigated the modulatory effects of EVs released by two phenotypically and genotypically distinct strains of <i>Histoplasma capsulatum</i> (G-217B and G-184A) on bone marrow-derived macrophages (BMDMs) and bone marrow-derived dendritic cells (BMDCs). Both host cells internalized <i>H. capsulatum</i> EVs, which appeared to elicit distinct functional responses. Treatment of BMDMs with EVs from either strain (EV_HcG-184A and EV_HcG-217B) increased IL-6 production with no significant changes in IL-10 levels. In contrast, BMDCs exposed with both EVs exhibited elevated levels of IL-6 and IL-10. Although EV treatment led to increased inducible nitric oxide synthase expression in BMDMs, it did not stimulate NO production. Remarkably, both EVs reduced the metabolic activity of phagocytes. Overnight exposure to EV_HcG-217B enhanced the phagocytosis of <i>H. capsulatum</i> yeasts by BMDMs; however, the phagolysosomal fusion was not affected. Notably, in DCs, EV_HcG-217B enhanced both the uptake and the viability of G-217B yeasts. Furthermore, incubation of <i>H. capsulatum</i> with its respective EVs promoted fungal growth, suggesting a self-stimulatory mechanism that may contribute to fungal persistence within host cells. Taken together, our results support the idea that <i>H. capsulatum</i> EVs are modulators of host–pathogen interaction, influencing phagocyte function and potentially contributing to fungal virulence.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"11 8","pages":"2342–2356"},"PeriodicalIF":3.8,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsinfecdis.5c00378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Fangfeng Yuan,&nbsp;Junru Cui,&nbsp;Tianlei Wang,&nbsp;Jane Qin,&nbsp;Ju Hyeong Jeon,&nbsp;Huiming Ding,&nbsp;Charles A. Whittaker,&nbsp;Renhuan Xu,&nbsp;Hong Cao and Jianzhu Chen*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"11 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsinfecdis.5c00029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Maria Cidinaria Silva Alves*,&nbsp;Mireli Santana Rego,&nbsp;Ruana Carolina Cabral da Silva,&nbsp;Rousilândia de Araújo Silva,&nbsp;Igor Eduardo Silva Arruda,&nbsp;Sérgio de Sá Leitão Paiva-Júnior and Valdir de Queiroz Balbino*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"11 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsinfecdis.5c00250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}