ACS Infectious Diseases最新文献

{"title":"Synergistic Paradigms in Infection Control: A Review on Photodynamic Therapy as an Adjunctive Strategy to Antibiotics.","authors":"Jennifer Machado Soares, Thaila Quatrini Corrêa, Claudia Patricia Barrera Patiño, Isabella Salgado Gonçalves, Gabriel Grube Dos Santos, Gabriela Gomes Guimarães, Rebeca Vieira de Lima, Thalita Hellen Nunes Lima, Bruna Carolina Corrêa, Taina Cruz de Souza Cappellini, Maria Vitória Silva Pereira, Anna Luiza França de Oliveira Resende, Vladislav V Yakovlev, Kate Cristina Blanco, Vanderlei Salvador Bagnato","doi":"10.1021/acsinfecdis.5c00369","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00369","url":null,"abstract":"<p><p>The increasing threat of antimicrobial resistance necessitates developing novel strategies to enhance the efficacy of existing antibiotics. This review explores the potential of antimicrobial photodynamic therapy (aPDT) as an adjunctive approach to antibiotic therapy. A systematic literature search was conducted in major scientific databases, focusing on studies published in the past decade investigating the synergistic effects of aPDT with antibiotics. Selected articles were analyzed based on their experimental approaches, bacterial targets, photodynamic parameters, and reported treatment outcomes. aPDT induces bacterial cell damage by generating reactive oxygen species (ROS), enhancing antibiotic susceptibility, and reducing required dosages. Furthermore, the review highlights promising research on optimizing treatment parameters and antibiotic combination strategies to maximize therapeutic outcomes. Despite its potential, aPDT faces obstacles to treatment standardization, variability in bacterial responses, and clinical implementation hurdles. These challenges require standardized protocols, further in vivo studies, and regulatory advancements to integrate aPDT into mainstream antimicrobial therapy. Conclusion: The synergy between aPDT and antibiotics represents a promising frontier in infection control, offering a safer, more effective, and resistance-mitigating strategy for bacterial infections. Future research should focus on refining treatment parameters, assessing long-term clinical impacts, and facilitating the widespread adoption of aPDT as a complementary antimicrobial approach.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111453","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":"Call for Papers: Artificial Intelligence for Next-generation Anti-infective Discovery.","authors":"Mark Brönstrup, Jonathan M Stokes","doi":"10.1021/acsinfecdis.5c00793","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00793","url":null,"abstract":"","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084550","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":"Antifungal Efficacy of 3D-Cultured Palatal Mesenchymal Stem Cells and Their Secreted Factors against <i>Candida albicans</i>.","authors":"Mesude Bicer, Esengül Öztürk, Fatma Sener, Sema S Hakki, Özkan Fidan","doi":"10.1021/acsinfecdis.5c00657","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00657","url":null,"abstract":"<p><p><i>Candida albicans</i> is among the life-threatening fungal species and the primary contributor to hospital-acquired systemic infections, accounting for nearly 70% of all fungal infections worldwide. The current treatment primarily relies on azoles, pyrimidine analogs, polyenes, and echinocandins. However, growing antifungal resistance highlights the urgent need for the development of alternative treatments against <i>C. albicans</i>. Mesenchymal stem cells (MSCs) offer huge therapeutic potential for the treatment of <i>C. albicans</i>-associated diseases. In this study, palatal adipose tissue-derived MSCs (PAT-MSCs) and PAT-MSCs cultured in 3D biomaterial using nanofibrillar cellulose were tested against <i>C. albicans</i> strains ATCC 10231 and ATCC MYA 2876 using an <i>in vitro</i> antifungal activity assay. In addition, the conditioned medium from both PAT-MSCs and PAT-MSCs cultured in 3D hydrogel biomaterial (CM-PAT-MSCs-3D) were evaluated for their antifungal activities. The combined effect of PAT-MSCs and their secreted factors was also investigated. The expression of five antimicrobial peptide (AMP)-encoding genes was analyzed by quantitative real-time PCR. The expression of antimicrobial peptides was further confirmed via immunocytochemical staining. PAT-MSCs significantly inhibited the growth of <i>C. albicans</i> strains at varying inoculum concentrations (500 and 2000 CFU). Similarly, a comparable antifungal effect was observed when <i>Candida</i> strains were treated with PAT-MSC secreted factors alone. Statistical analysis revealed significant differences between the antifungal activities of PAT-MSCs and CM-PAT-MSCs. Lastly, the combination of PAT-MSCs and CM-PAT-MSC-3D led to a marked reduction in fungal growth, with inhibition rates of 99.75% and 99.91% for <i>C. albicans</i> ATCC 10231 and ATCC MYA-2876, respectively, at 500 CFU inocula. At 2000 CFU inocula, inhibition rates were 99.54% and 99.91%, respectively (****<i>P</i> ≤ 0.0001). These antifungal activities were further confirmed by using RT-PCR and immunocytochemical analysis. Our findings underscore a perspective on the potent antifungal activity of secreted factors from PAT-MSCs cultured within a 3D hydrogel matrix, specifically against various strains of <i>C. albicans</i>. Particularly, the combination of PAT-MSCs with their secreted factors represents a promising therapeutic platform, potentially offering a safer and more effective alternative to conventional antifungal treatments.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090776","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":"Sulfonyl Homoserine Lactones Are Tunable Probes to Inhibit the Quorum Sensing Receptor RhlR and Reduce Swarming Motility in <i>Pseudomonas aeruginosa</i>.","authors":"Guadalupe Aguirre-Figueroa, Diana A Morales Mijares, Isabel D Cannell, Irene M Stoutland, Helen E Blackwell","doi":"10.1021/acsinfecdis.5c00542","DOIUrl":"10.1021/acsinfecdis.5c00542","url":null,"abstract":"<p><p>We report non-native small molecules capable of inhibiting a key quorum sensing receptor─RhlR─in the opportunistic pathogen <i>Pseudomonas aeruginosa</i>. This protein is a member of the LuxR-type receptor family that is common to Gram-negative bacteria and recognizes <i>N-</i>acyl l-homoserine lactone (AHL) signals. RhlR has emerged as an increasingly important regulator of virulence pathways in <i>P. aeruginosa</i>, in concert with several other quorum sensing receptors, including LasR, QscR, and PqsR. Chemical inhibition of RhlR represents an approach to both study the role of RhlR in this quorum sensing signaling hierarchy and attenuate infection by <i>P. aeruginosa</i>. Small-molecule RhlR antagonists with high potencies and defined modes of action remain relatively scarce, however. AHL analogs with non-native acyl side chains represent a well-studied class of LuxR-type receptor modulators, but replacement of the native amide with alternate isosteres has been far less examined. In the current study, we investigated the activity of a series of sulfonamide AHL analogs as RhlR antagonists using transcriptional reporter assays. We identified <i>meta</i>-substituted aryl- and short-chain alkylsulfonyl lactones as potent and efficacious classes of synthetic RhlR antagonists. The activity profiles of the aryl derivatives were readily tuned via altering the position and electronics of aryl ring substituents. The most potent antagonists were active in <i>P. aeruginosa</i> and could significantly reduce its swarming motility, a key virulence determinant. Computational modeling revealed these compounds can be accommodated within the RhlR ligand-binding site and certain interactions may be required for high inhibitory potency.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073987","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":"HIV and Aging: Impacts on the Central Nervous System and Insights on Animal Models.","authors":"Chen Zhang, George Z Ji, Larisa Y Poluektova, Santhi Gorantla, Prasanta K Dash","doi":"10.1021/acsinfecdis.5c00269","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00269","url":null,"abstract":"<p><p>Aging is an inevitable biological process in living species characterized by the continuous deterioration of physiological, molecular, cellular, biochemical, and functional changes. While people living with human immunodeficiency virus (HIV) infection (PLWH) are experiencing improved life expectancy due to advancements in the combinatorial antiretroviral therapy (cART) paradigms, they continue to face a higher burden of aging-associated comorbidities like diabetes, cancer, frailty, and pulmonary, liver, cardiovascular, and neurological disorders. Aging and HIV infection have been shown to have negative impacts on the form and function of the central nervous system (CNS). Whether HIV alone or cART alone or both HIV and cART acting synergistically contribute more to the aging-associated perturbations is not well studied because of limitations regarding longitudinal clinical sample availability and suitable human-aging mimicking animal models. With the current knowledge relying heavily on noninvasive approaches or postmortem specimens, gaps persist in understanding how latent HIV infection and chronic ART intake interact with the biological processes of aging in the CNS. In this article, we discussed the advantages and limitations of the models available to study aging and aim to focus on CNS-associated aging in a long-term human immune system carrying rodent model, which could not only advance the development of adjunctive therapies, when combined with cART but may also mitigate or slow the \"accelerated\" aging observed in older HIV-positive populations.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068665","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":"Biocompatible Guanidine-Functionalized Compounds with Biofilm and Membrane Disruptive Activity Against MRSA.","authors":"Pamella Fukuda de Castilho, Luana Janaína de Campos, Audifás-Salvador Matus-Meza, Huihua Xing, Diana Liz Jimenez Rolão, Fernanda Galvão, Fabiana Gomes da Silva Dantas, Rongguo Ren, Cameron Dobrotka, Fábio Aguiar-Alves, Martin Conda-Sheridan, Kelly Mari Pires de Oliveira","doi":"10.1021/acsinfecdis.5c00642","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00642","url":null,"abstract":"<p><p>Three guanidine-functionalized 3,4-dihydropyrimidin-2(1<i>H</i>)-imine compounds (<b>5a</b>, <b>5b</b>, <b>5c</b>) were synthesized from 3,5-diaryldiene-4-piperidone and evaluated for antibacterial and antibiofilm activity against <i>Staphylococcus aureus</i>, CA-MRSA and HA-MRSA. The compounds showed bacteriostatic effects (MICs: 2.34-4.68 μg/mL). In vitro antibiofilm potential was demonstrated by significant reductions in biomass and metabolic activity, and structural analyses via SEM and fluorescence microscopy. Ex vivo antibiofilm activity was confirmed in porcine skin model. RT-qPCR revealed downregulation of biofilm associated virulence genes, indicating a multifactorial mechanism. Confocal microscopy showed increased levels of extracellular DNA and proteins, suggesting disruption of the biofilm matrix. Membrane interaction assays demonstrated time- and dose-dependent effects, suggesting a complementary mechanism of action. Compounds <b>5a</b> and <b>5c</b> exhibited synergistic and additive effects with oxacillin. The compounds were stable intracellularly, and resistance studies revealed low induction potential. Biocompatibility was confirmed by lack of mutagenicity, hemolysis, or cytotoxicity. Moreover, in vivo efficacy was demonstrated by survival of <i>Tenebrio molitor</i> larvae infected with <i>S. aureus</i> and treated. These guanidine-based compounds are promising candidates for new MRSA drug development.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068628","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":"Staphylococcal Functional Amyloids: Structure, Pathogenic Roles, Biofilm Fortification, and Inhibition Strategies.","authors":"Nikita Admane, Sumit Biswas","doi":"10.1021/acsinfecdis.5c00572","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00572","url":null,"abstract":"<p><p>Amyloid aggregates, which are hallmarks of various human diseases, show promising roles in almost all life forms. In the past few years, there has been a significant broadening of the diverse roles that bacterial functional amyloids play in nature, expanding the horizons of these fibrillar assemblies. Herein, we provide a review of the current understanding of staphylococcal functional amyloids, their multifaceted roles in pathogenesis, and strengthening biofilm-associated antibiotic resistance. This review aims to explore how staphylococcal biofilm strengthening amyloidogenic proteins and peptides, particularly derived from <i>Staphylococcus aureus</i> and <i>Staphylococcus epidermidis</i>, can act as dual-edged swords supporting pathogenesis in the planktonic stages and triggering infections in biofilms. We outline the different amyloid fibrillar species derived from these proteins/peptides and the molecules that have been discovered to target their amyloid transformation. This review also highlights how the noncanonical structural polymorphisms of these extracellular fibrillar amyloids are responsible for their functional diversity and discusses the techniques that are used recently for exploring staphylococcal amyloid structure assortment.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051313","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":"Call for Papers: Nontuberculous Mycobacterial (NTM) Pathogens─Biology, Infection, and Drug Discovery","authors":"Sidharth Chopra,&nbsp;Arunava Dasgupta and Laurent Kremer,&nbsp;","doi":"10.1021/acsinfecdis.5c00740","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00740","url":null,"abstract":"","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"11 9","pages":"2372"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036524","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 High-Throughput Broad Neutralizing Antibody Assay for Detecting SARS-CoV-2 Variant Immunity in Population.","authors":"Xiaohan Zhang, Yajie Wang, Mansheng Li, Haolong Li, Xiaomei Zhang, Xingming Xu, Qingqing Ma, Di Hu, Yan Jia, Te Liang, Yunping Zhu, Surbhi Bihani, Sanjeeva Srivastava, Manuel Fuentes, Yongzhe Li, Xiaoxu Han, Bingwei Wang, Xiaobo Yu","doi":"10.1021/acsinfecdis.5c00402","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00402","url":null,"abstract":"<p><p>Detecting neutralizing antibodies (NAbs) to SARS-CoV-2 variants that are evolved is crucial to know the escape of host immunity to the newly arising variants. To address this need, we developed a high-throughput broad neutralizing antibody (bNAb) assay using flow cytometry with magnetic-fluorescent microspheres for detecting NAbs against diverse SARS-CoV-2 variants. The assay is rapid, reliable, and 35-fold more sensitive than Luminex technology. Our results highly correlated with the IgG serological assay (<i>R</i> = 0.90), the FDA-approved cPass sVNT assay (<i>R</i> = 0.92), pseudovirus-based neutralization assay (<i>R</i> = 0.96, 0.66, 0.65), and live virus-based neutralization assay (<i>R</i> = 0.79, 0.64). When applied to 56 healthy individuals receiving third-dose vaccines (18 CoronaVac; 38 ZF2001) and 35 HIV patients with breakthrough infection of COVID-19 (16 with CD4+ < 350 cells/μL; 19 with CD4+ > 500 cells/μL), results showed that the Omicron BA.1-BA.5 variants exhibited significant resistance to inactivated vaccines in healthy individuals. In HIV patients, the breakthrough infection of Omicron BA.5.2 or BF.7 variants can induce broad neutralizing activity to non-Omicron and Omicron variants together with vaccination. Notably, the levels of NAbs against most of the SARS-CoV-2 variants are much lower in the decreased immunity of HIV patients (CD4+ < 350 cells/μL) compared to the recovered immunity (CD4+ > 500 cells/μL), indicating that maintenance of the immune system is crucial for NAb production. Altogether, our high-throughput proteomics platform represents a powerful tool for the detection of bNAbs in the population and may inform the development of more effective COVID-19 vaccines and vaccination strategies in the future.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051324","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":"Metabolic Tagging Reveals Surface-Associated Lipoproteins in Mycobacteria.","authors":"Lia A Parkin, Kindra L Becker, Julian P Maceren, Aseem Palande, Neetika Jaisinghani, Mary L Previti, Jessica C Seeliger","doi":"10.1021/acsinfecdis.5c00365","DOIUrl":"10.1021/acsinfecdis.5c00365","url":null,"abstract":"<p><p>Mycobacteria such as the causative agent of tuberculosis, <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), encode over 100 bioinformatically predicted lipoproteins. Despite the importance of these post-translationally modified proteins for mycobacterial survival, many remain experimentally unconfirmed. Here we characterized in <i>Mtb</i> and <i>M. smegmatis</i> (<i>Msm</i>) the metabolic incorporation of several modified fatty acids as a facile method of adding chemical groups that enable downstream applications such as detection and enrichment of lipid-modified proteins. We further showed for azido palmitic acid in <i>Msm</i> that incorporation is an active process dependent on the lipoprotein biosynthesis pathway and that a subset of these lipid-modified proteins are associated with the mycobacterial cell surface. Because mycobacteria do not encode known lipoprotein transporters, these data have implications for uncovering the roles of lipoproteins and the possible transport processes involved. Our findings and the tools we validated will enable the further study of pathways related to lipoprotein function in mycobacteria and other bacteria in which lipoproteins remain poorly understood.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051319","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}