ACS Infectious Diseases最新文献

Inhibitor Affinity Differs among Clinical Variants of IMP Metallo-β-Lactamases: Analysis and Implications for Inhibitor Design. IMP金属β-内酰胺酶的临床变异对抑制剂的亲和力不同：对抑制剂设计的分析和影响

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-24 DOI: 10.1021/acsinfecdis.5c00138

Caitlyn A Thomas, John Paul Alao, Thomas Smisek, Zishuo Cheng, Christopher R Bethel, Kundi Yang, Ikponwmosa Obaseki, Richard C Page, Robert A Bonomo, Peter Oelschlaeger, Walter Fast, Andrea N Kravats, Michael W Crowder

{"title":"Inhibitor Affinity Differs among Clinical Variants of IMP Metallo-β-Lactamases: Analysis and Implications for Inhibitor Design.","authors":"Caitlyn A Thomas, John Paul Alao, Thomas Smisek, Zishuo Cheng, Christopher R Bethel, Kundi Yang, Ikponwmosa Obaseki, Richard C Page, Robert A Bonomo, Peter Oelschlaeger, Walter Fast, Andrea N Kravats, Michael W Crowder","doi":"10.1021/acsinfecdis.5c00138","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00138","url":null,"abstract":"β-Lactam-resistant bacterial infections are a serious concern worldwide. A common mechanism of β-lactam resistance is the expression of β-lactamases, which are capable of hydrolyzing the β-lactam bond in the most commonly used β-lactam antibiotics. Metallo-β-lactamases (MBLs) utilize 1 or 2 zinc ions for catalysis. One of the three most clinically relevant MBLs is Imipenemase (IMP). An important potential way to combat MBLs is to use an inhibitor in combination with an existing β-lactam drug. The current study investigates the mechanism of inhibition of preclinical boronic acid β-lactamase inhibitor RPX 7546 and mercaptomethyl bisthiazolidine D-CS319, which are two previously reported MBL inhibitors, with IMP-1 and its variant IMP-78 (V67F/S262G), chosen due to its improved efficiency hydrolyzing carbapenem β-lactams. A combination of analytical and biochemical experiments and in silico modeling collectively offer a comprehensive understanding of the mechanism of inhibition by these two inhibitors. Our studies show that RPX 7546 is a less effective inhibitor of IMP-78, compared to IMP-1, while D-CS319 shows equally effective inhibition of both enzymes. The findings can be explained in light of the evolution of IMP-78 to overcome structural differences of substrates. Studying inhibitors with variants of clinically relevant MBLs is an area that is growing in importance in the literature. The findings of the current study highlight its significance and the urgent need for the discovery of an MBL inhibitor for clinical use.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697083","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

Structural Basis for Postfusion-Specific Binding to the Respiratory Syncytial Virus F Protein by the Canonical Antigenic Site I Antibody 131-2a. 典型抗原位点I抗体131-2a与呼吸道合胞病毒F蛋白融合后特异性结合的结构基础

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-22 DOI: 10.1021/acsinfecdis.5c00368

Weiwei Peng, Marta Šiborová, Xuesheng Wu, Wenjuan Du, Douwe Schulte, Matti F Pronker, Cornelis A M de Haan, Joost Snijder

{"title":"Structural Basis for Postfusion-Specific Binding to the Respiratory Syncytial Virus F Protein by the Canonical Antigenic Site I Antibody 131-2a.","authors":"Weiwei Peng, Marta Šiborová, Xuesheng Wu, Wenjuan Du, Douwe Schulte, Matti F Pronker, Cornelis A M de Haan, Joost Snijder","doi":"10.1021/acsinfecdis.5c00368","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00368","url":null,"abstract":"The respiratory syncytial virus (RSV) fusion (F) protein is a major target of antiviral antibodies following natural infection or vaccination and is responsible for mediating fusion between the viral envelope and the host membrane. The fusion process is driven by a large-scale conformational change in F, switching irreversibly from the metastable prefusion state to the stable postfusion conformation. Previous research has identified six distinct antigenic sites in RSV-F, termed sites Ø, I, II, III, IV, and V. Of these, only antigenic site I is fully specific to the postfusion conformation of F. A monoclonal antibody 131-2a that specifically targets postfusion F has been widely used as a research tool to probe for postfusion F and to define antigenic site I in serological studies, yet its sequence and precise epitope have remained unknown. Here, we use mass spectrometry-based de novo sequencing of 131-2a to reverse engineer a recombinant product and study the epitope to define antigenic site I with molecular detail, revealing the structural basis for the antibody's specificity toward postfusion RSV-F.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688318","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

Studies on Developing a Preclinical Candidate to Fight Helicobacter Pylori Infection. 开发抗幽门螺杆菌感染的临床前候选药物的研究。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-19 DOI: 10.1021/acsinfecdis.5c00383

Haritha Dilip, Deepika Khasa, Ramya V K, Parvinder Kaur, Siva Shanmugam, Naveenkumar Chakenalli, Radhakrishanan Shandil, Shridhar Narayanan, Vijay Thiruvenkatam, Sivapriya Kirubakaran

{"title":"Studies on Developing a Preclinical Candidate to Fight Helicobacter Pylori Infection.","authors":"Haritha Dilip, Deepika Khasa, Ramya V K, Parvinder Kaur, Siva Shanmugam, Naveenkumar Chakenalli, Radhakrishanan Shandil, Shridhar Narayanan, Vijay Thiruvenkatam, Sivapriya Kirubakaran","doi":"10.1021/acsinfecdis.5c00383","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00383","url":null,"abstract":"Helicobacter pylori (H. pylori) infection, a precursor to gastritis and gastric cancer, is one of the many infectious diseases that pose a challenge to the progress of developing nations. The present study is the first report on the development of a set of benzopyridine-fused benzimidazoles, leading to the identification of a lead and its further optimization as a potential preclinical candidate for treating H. pylori infection. The designed synthetic method for these derivatives is devoid of toxic chemicals and sophisticated reaction setups, using economical and readily available chemicals to produce benzopyridine-fused (namely, quinoline/isoquinoline-fused) benzimidazole derivatives in moderate-to-good yields. These small molecules showed promising H. pylori growth inhibition, and a lead molecule was identified and evaluated for its antibacterial potential. Following the promising results of the growth inhibition displayed by this series of inhibitors, lead optimization studies were carried out on the best inhibitor of H. pylori growth, highlighting the possibility of developing this core molecule for preclinical trials.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666639","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

Netupitant Exhibits Potent Activity on Mycobacterium tuberculosis Persisters. 尼图匹坦对结核分枝杆菌表现出强有力的活性。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-18 DOI: 10.1021/acsinfecdis.5c00298

Hassan E Eldesouky, Richard M Jones, Shabber Mohammed, Enming Xing, Pui-Kai Li, David R Sherman

{"title":"Netupitant Exhibits Potent Activity on Mycobacterium tuberculosis Persisters.","authors":"Hassan E Eldesouky, Richard M Jones, Shabber Mohammed, Enming Xing, Pui-Kai Li, David R Sherman","doi":"10.1021/acsinfecdis.5c00298","DOIUrl":"10.1021/acsinfecdis.5c00298","url":null,"abstract":"In Mycobacterium tuberculosis (Mtb), persisters are genotypically drug-sensitive bacteria that nonetheless survive antibiotic treatment. Persisters contribute to prolonged TB treatment duration and relapse risk, highlighting the need for new therapeutic strategies to effectively eliminate these tolerant subpopulations. In this study, we screened 2,336 FDA-approved compounds to identify agents that enhance the sterilizing activity of standard anti-TB drugs and prevent the regrowth of persisters. Netupitant (NTP), an FDA-approved antiemetic, emerged as a promising candidate. In combination with isoniazid (INH) and rifampicin (RIF), NTP eliminated viable Mtb cells, achieving a >6-log reduction in colony-forming units (CFUs), compared to the 2.5-log reduction observed with INH-RIF alone. NTP also demonstrated broad-spectrum efficacy, enhancing the activity of multiple TB drugs, including ethambutol, moxifloxacin, amikacin, and bedaquiline. Notably, NTP retained its potency under hypoxic and caseum-mimicking conditions, both of which are known to enrich for non-replicating, drug-tolerant cells. The mammalian target of NTP, the G protein-coupled receptor NK-1, is absent in bacteria, raising the possibility that the NTP target in bacteria is novel. To begin assessing this possibility, we performed transcriptomics and found that NTP significantly upregulates multiple oxidative stress response-associated genes, while downregulating pathways linked to protein synthesis, electron transport chain activities, and ATP synthesis. While further studies are required to decipher mechanisms of action and the resistance profile of NTP, and to assess its in vivo efficacy, these findings underscore its potential as a promising adjunct to existing TB therapies.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657835","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

Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity. 具有抗甲病毒活性的基孔肯雅nsP2解旋酶的对体选择性化学探针。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-18 DOI: 10.1021/acsinfecdis.5c00351

Bose Muthu Ramalingam, Hans J Oh, John D Sears, Chun-Hsing Chen, Anand Vala, Shubin Liu, Kacey M Talbot, Mohammed Anwar Hossain, Peter J Brown, Scott Houliston, Julia Garcia Perez, Fengling Li, Meareg G Amare, Peter Halfmann, Jessica L Smith, Alec J Hirsch, Cheryl H Arrowsmith, Levon Halabelian, Ava Vargason, Rafael M Couñago, Jamie J Arnold, Craig E Cameron, Nathaniel J Moorman, Mark T Heise, Timothy M Willson

{"title":"Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity.","authors":"Bose Muthu Ramalingam, Hans J Oh, John D Sears, Chun-Hsing Chen, Anand Vala, Shubin Liu, Kacey M Talbot, Mohammed Anwar Hossain, Peter J Brown, Scott Houliston, Julia Garcia Perez, Fengling Li, Meareg G Amare, Peter Halfmann, Jessica L Smith, Alec J Hirsch, Cheryl H Arrowsmith, Levon Halabelian, Ava Vargason, Rafael M Couñago, Jamie J Arnold, Craig E Cameron, Nathaniel J Moorman, Mark T Heise, Timothy M Willson","doi":"10.1021/acsinfecdis.5c00351","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00351","url":null,"abstract":"Chikungunya virus (CHIKV) replication relies on the multifunctional nsP2 protein, making it an attractive target for antiviral drug discovery. Here, we report the resolution of oxaspiropiperidine 1, a first-in-class inhibitor of the CHIKV nsP2 RNA helicase (nsP2hel), into its constitutive enantiomers and characterization of their antiviral activity. The enantiomer (R)-1 exhibited potent inhibition of viral replication, nsP2hel ATPase activity, and dsRNA unwinding, while the (S)-1 enantiomer was >100-fold less active. The (R)-1 enantiomer also demonstrated a high selectivity for CHIKV over other RNA viruses and for nsP2hel over other RNA helicases. Direct binding of (R)-1 to the nsP2hel protein was confirmed by 19F NMR. Biophysical and structural studies revealed conformational polymorphism in the spirocyclic scaffold of (R)-1, suggesting a potential role of thermal mobility of the ligand in allosteric inhibition of nsP2hel. Collectively, these findings designate (R)-1 (RA-NSP2-1) as a high-quality chemical probe and (S)-1 (RA-NSP2-1N) as a negative control for probing the biology of alphavirus RNA helicases.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663837","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

Identification and Evaluation of Non-Nucleosidic MTase Inhibitors against SARS-CoV-2 nsp14 with Lower-Micromolar Anti-Coronavirus Activity. 具有低微摩尔抗冠状病毒活性的SARS-CoV-2 nsp14非核苷类MTase抑制剂的鉴定和评价

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-17 DOI: 10.1021/acsinfecdis.4c01044

Yuanmei Wen, Jun Zhou, Fan Pan, Peisen Zheng, Fengxia Zhong, Sidi Yang, Qianhan Ma, Deyin Guo, Xumu Zhang, Qifan Zhou, Yingjun Li

{"title":"Identification and Evaluation of Non-Nucleosidic MTase Inhibitors against SARS-CoV-2 nsp14 with Lower-Micromolar Anti-Coronavirus Activity.","authors":"Yuanmei Wen, Jun Zhou, Fan Pan, Peisen Zheng, Fengxia Zhong, Sidi Yang, Qianhan Ma, Deyin Guo, Xumu Zhang, Qifan Zhou, Yingjun Li","doi":"10.1021/acsinfecdis.4c01044","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c01044","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory infections ranging from mild to severe, posing significant public health risks. The emergence of new variants highlights the need for inhibitors targeting conserved nonstructural proteins like nsp14, a key N7-methyltransferase (MTase) critical for viral RNA capping, immune evasion, and replication. Here, we screened 131 compounds using a drug repurposing approach and identified five candidates that inhibit MTase activity. Bobcat339 showed significant inhibition (IC50 = 21.6 μM) and binding affinity (ΔTm = +3.9 °C). It also reduced the replication of HCoV-229E and SARS-CoV-2 in infected Huh7 cells (EC50 = 29.8 and 28.4 μM, respectively). Molecular docking suggested Bobcat339 binds the SAM-binding pocket of nsp14 MTase. These results identify Bobcat339 as a promising lead for developing selective, non-nucleoside nsp14 inhibitors, supporting further structural optimization and preclinical evaluation.","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":"144657834","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

Discovery of a Widespread Polyamine-Low-Molecular-Weight Thiol Hybrid Pathway in Clostridioides difficile. 艰难梭菌中广泛存在的多胺-低分子量硫醇杂交途径的发现。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-17 DOI: 10.1021/acsinfecdis.5c00286

Rachelle L Hunt, Joonseok Oh, Abhishek Jain, Ting-Hao Kuo, Domenica Berardi, Wenya Jian, Deguang Song, Qihao Wu, Andrew L Goodman, Noah W Palm, Michael Zimmermann, Caroline H Johnson, Jason M Crawford

{"title":"Discovery of a Widespread Polyamine-Low-Molecular-Weight Thiol Hybrid Pathway in Clostridioides difficile.","authors":"Rachelle L Hunt, Joonseok Oh, Abhishek Jain, Ting-Hao Kuo, Domenica Berardi, Wenya Jian, Deguang Song, Qihao Wu, Andrew L Goodman, Noah W Palm, Michael Zimmermann, Caroline H Johnson, Jason M Crawford","doi":"10.1021/acsinfecdis.5c00286","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00286","url":null,"abstract":"Clostridioides difficile infection can cause severe inflammation in the gastrointestinal (GI) tract, leading to diarrhea, colitis, and an increased risk of colorectal cancer. Colonization of C. difficile is associated with microbial community-level changes in the expression of polyamine and polyamine precursor biosynthesis genes. Polyamines are abundant cationic metabolites that serve indispensable functions for all kingdoms, particularly in gut homeostasis. Catabolism of the polyamine precursors arginine and ornithine offers C. difficile supplemental nutrition while subverting host immunity, yet existing models of C. difficile metabolism are incomplete regarding polyamines with comparable importance in the gut (e.g., spermidine). In this study, we conducted feeding studies with isotope-labeled polyamines and discovered a network of low-molecular-weight thiol (LMWT) molecules termed clostridithiols (CSHs) constructed from polyamines conjugated with N-acetylcysteine (NAC) moieties. NAC is clinically used as a mucolytic agent and is a well-established redox molecule. Through the analysis of a human microbiota diversity collection, we established that these previously uncharacterized hybrid metabolites are widely detected in Firmicutes and Bacteroidetes. A genetic screen using DNA from an alternative CSH producerBacteroides uniformis enabled the identification and validation of a two-gene operon, including a gene encoding a domain of unknown function, that was conserved in both producing organisms and other members of the microbiome. CSH abundance in GI mucosal biopsies positively correlated with colorectal cancer compared with matched healthy control samples. These studies indicate that human microbial metabolism broadly unites polyamine and LMWT functionalities to generate metabolites that may be associated with disease.","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":"144647953","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

Targeting G-Quadruplex with Bis-thiourea Compounds Inhibits SARS-CoV-2 Replication. 双硫脲化合物靶向g -四重体抑制SARS-CoV-2复制

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-17 DOI: 10.1021/acsinfecdis.5c00095

Shogo Sasaki, Shogo Nakajima, Rena Nohara, Hiroyuki Endo, Norito Takeuchi, Taiji Oyama, Naoya Iwano, Kaori Tsukakoshi, Kazunori Ikebukuro, Akira Shiraishi, Kazuo Nagasawa, Koichi Watashi, Masayuki Tera

{"title":"Targeting G-Quadruplex with Bis-thiourea Compounds Inhibits SARS-CoV-2 Replication.","authors":"Shogo Sasaki, Shogo Nakajima, Rena Nohara, Hiroyuki Endo, Norito Takeuchi, Taiji Oyama, Naoya Iwano, Kaori Tsukakoshi, Kazunori Ikebukuro, Akira Shiraishi, Kazuo Nagasawa, Koichi Watashi, Masayuki Tera","doi":"10.1021/acsinfecdis.5c00095","DOIUrl":"10.1021/acsinfecdis.5c00095","url":null,"abstract":"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.","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":"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}

引用次数: 0

Smart Wound Dressing with Real-Time Colorimetric Detection of Antimicrobial Resistance and Infection. 实时比色法检测抗菌药物耐药性和感染的智能伤口敷料。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-17 DOI: 10.1021/acsinfecdis.5c00256

Vaishnavi N, Ramakrishnan Ganesan, Jayati Ray Dutta

{"title":"Smart Wound Dressing with Real-Time Colorimetric Detection of Antimicrobial Resistance and Infection.","authors":"Vaishnavi N, Ramakrishnan Ganesan, Jayati Ray Dutta","doi":"10.1021/acsinfecdis.5c00256","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00256","url":null,"abstract":"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-d-galactopyranoside (CPRG) for β-galactosidase-based rapid colorimetric detection of pathogenic infections and (ii) nitrocefin for identifying β-lactamase-mediated AMR. Extensive in vitro and ex vivo 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.","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":"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}

引用次数: 0

Pse-T2-Based Short Peptides with Broad-Spectrum Antimicrobial Activity, Stability, and Safety Combat MDR Staphylococcus aureus In Vitro and in Mouse Infection Model. 具有广谱抗菌活性、稳定性和安全性的pse - t2短肽在体外和小鼠感染模型中对抗MDR金黄色葡萄球菌。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-17 DOI: 10.1021/acsinfecdis.4c01034

Hee Kyoung Kang, Yoonkyung Park

引用次数: 0