ACS Infectious Diseases最新文献_第3页

Extracellular vesicles from Distinct Histoplasma capsulatum Strains Modulate Phagocyte Function and Promote Fungal Persistence. 不同荚膜组织浆菌株的细胞外囊泡调节吞噬细胞功能并促进真菌的持久性。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-13 DOI: 10.1021/acsinfecdis.5c00378

Taiane N Souza, Alessandro F Valdez, Ana Claudia G Zimbres, Bianca A G Sena, Flavia C G Reis, Marcio L Rodrigues, Daniel Zamith-Miranda, Allan J Guimarães, Alessandra A Filardy, Joshua D Nosanchuk, Leonardo Nimrichter

{"title":"Extracellular vesicles from Distinct Histoplasma capsulatum Strains Modulate Phagocyte Function and Promote Fungal Persistence.","authors":"Taiane N Souza, Alessandro F Valdez, Ana Claudia G Zimbres, Bianca A G Sena, Flavia C G Reis, Marcio L Rodrigues, Daniel Zamith-Miranda, Allan J Guimarães, Alessandra A Filardy, Joshua D Nosanchuk, Leonardo Nimrichter","doi":"10.1021/acsinfecdis.5c00378","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00378","url":null,"abstract":"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 Histoplasma capsulatum (G-217B and G-184A) on bone marrow-derived macrophages (BMDMs) and bone marrow-derived dendritic cells (BMDCs). Both host cells internalized H. capsulatum EVs, which appeared to elicit distinct functional responses. Treatment of BMDMs with EVs from either strain (EVHcG-184A and EVHcG-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 EVHcG-217B enhanced the phagocytosis of H. capsulatum yeasts by BMDMs; however, the phagolysosomal fusion was not affected. Notably, in DCs, EVHcG-217B enhanced both the uptake and the viability of G-217B yeasts. Furthermore, incubation of H. capsulatum 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 H. capsulatum EVs are modulators of host-pathogen interaction, influencing phagocyte function and potentially contributing to fungal virulence.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-11

Fangfeng Yuan, Junru Cui, Tianlei Wang, Jane Qin, Ju Hyeong Jeon, Huiming Ding, Charles A. Whittaker, Renhuan Xu, Hong Cao and Jianzhu Chen*,

引用次数: 0

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-11

Maria Cidinaria Silva Alves*, Mireli Santana Rego, Ruana Carolina Cabral da Silva, Rousilândia de Araújo Silva, Igor Eduardo Silva Arruda, Sérgio de Sá Leitão Paiva-Júnior and Valdir de Queiroz Balbino*,

引用次数: 0

Halogenated Sulfono-γ-AApeptides Modified Cationic AMPs Have Enhanced Stability and Therapeutic Potential against Clinically Important MDR Infections. 卤化磺酰γ- α肽修饰的阳离子AMPs具有增强稳定性和治疗临床重要耐多药感染的潜力。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-11 Epub Date: 2025-06-12 DOI: 10.1021/acsinfecdis.5c00312

Xiaomin Guo, Yingying An, Tiantian Yan, Yue Jia, Ruoyan Jiao, Xinyu Cai, Weili Yang, Guangjun Bao, Wangsheng Sun, Wenle Yang, Ningning Lu, Junqiu Xie

{"title":"Halogenated Sulfono-γ-AApeptides Modified Cationic AMPs Have Enhanced Stability and Therapeutic Potential against Clinically Important MDR Infections.","authors":"Xiaomin Guo, Yingying An, Tiantian Yan, Yue Jia, Ruoyan Jiao, Xinyu Cai, Weili Yang, Guangjun Bao, Wangsheng Sun, Wenle Yang, Ningning Lu, Junqiu Xie","doi":"10.1021/acsinfecdis.5c00312","DOIUrl":"10.1021/acsinfecdis.5c00312","url":null,"abstract":"Antimicrobial peptides have garnered increasing attention and are anticipated to address the growing crisis of antibiotic resistance. However, their inadequate proteolytic stability poses significant challenges for clinical development. In this study, we present a highly effective strategy to overcome the limitations by introducing multiple halogenated sulfono-γ-AApeptides into cationic AMP Feleucin-K3. Surprisingly, K162 and K174, which feature sulfono-γ-AApeptide modifications containing iodinated or trifluoromethyl groups, exhibit powerful antibacterial and antibiofilm activities, while having significantly improved stability. Furthermore, they exhibited low resistance tendencies and were less susceptible to cross-resistance in comparison to antibiotics. Additionally, the two analogs exhibited superior safety and therapeutic potential compared to polymyxin B against pneumonia induced by multidrug-resistant P. aeruginosa. For skin- and catheter-biofilm-related infections caused by MRSA, K162, and K174 displayed comparable therapeutic effects compared to vancomycin. In conclusion, K162 and K174 are considered novel antimicrobial alternatives to combat multidrug-resistant bacterial infections.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"2018-2036"},"PeriodicalIF":4.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281667","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

Inhibitors of the Bacterioferritin Ferredoxin Complex Dysregulate Iron Homeostasis and Kill Acinetobacter baumannii and Biofilm-Embedded Pseudomonas aeruginosa Cells. 细菌铁蛋白-铁氧还蛋白复合物的抑制剂调节铁稳态失调并杀死鲍曼不动杆菌和铜绿假单胞菌生物膜包埋细胞。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-11 Epub Date: 2025-06-09 DOI: 10.1021/acsinfecdis.5c00209

Alexanndra M Behm, Huili Yao, Emmanuel C Eze, Suliat A Alli, Simon D P Baugh, Ebenezer Ametsetor, Kendall M Powell, Kevin P Battaile, Steve Seibold, Scott Lovell, Richard A Bunce, Allen B Reitz, Mario Rivera

{"title":"Inhibitors of the Bacterioferritin Ferredoxin Complex Dysregulate Iron Homeostasis and Kill Acinetobacter baumannii and Biofilm-Embedded Pseudomonas aeruginosa Cells.","authors":"Alexanndra M Behm, Huili Yao, Emmanuel C Eze, Suliat A Alli, Simon D P Baugh, Ebenezer Ametsetor, Kendall M Powell, Kevin P Battaile, Steve Seibold, Scott Lovell, Richard A Bunce, Allen B Reitz, Mario Rivera","doi":"10.1021/acsinfecdis.5c00209","DOIUrl":"10.1021/acsinfecdis.5c00209","url":null,"abstract":"In Pseudomonas aeruginosa, the iron storage protein bacterioferritin (Bfr) contributes to buffering cytosolic free iron concentrations by oxidizing Fe2+ and storing the resultant Fe3+ in its internal cavity, and by forming a complex with a cognate ferredoxin (Bfd) to reduce the stored Fe3+ and mobilize Fe2+ to the cytosol. Small molecule derivatives of 4-aminoisoindoline-1,3-dione designed to bind P. aeruginosa Bfr (Pa Bfr) at the Bfd binding site accumulate in the P. aeruginosa cell, block the Pa Bfr-Bfd complex, inhibit iron mobilization from Pa Bfr, elicit an iron starvation response, are bacteriostatic to planktonic cells, and are bactericidal to biofilm-entrenched cells. A structural alignment of Pa Bfr and Acinetobacter baumannii Bfr (Ab Bfr) showed strong conservation of the Bfd binding site on Ab Bfr. Accordingly, the small molecule inhibitors of the Pa Bfr-Bfd complex accumulate in the A. baumannii cells, elicit an iron starvation response, are bactericidal to planktonic cells, and exhibit synergy with existing antibiotics. These findings indicate that the inhibition of iron mobilization from Bfr may be an antimicrobial strategy applicable to other Gram-negative pathogens.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"1983-1993"},"PeriodicalIF":4.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256629","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}

引用次数: 0

Single-Sample Melt-Based Screening for Rifampicin Susceptibility in the Emerging Mutation Hotspot at rpoB Codon 491. rpoB密码子491新突变热点的单样本熔融筛选利福平敏感性

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-11 Epub Date: 2025-06-17 DOI: 10.1021/acsinfecdis.5c00150

Nicole A Malofsky, Swayashreyee B Dhungel, Megan E Pask, Frederick R Haselton

{"title":"Single-Sample Melt-Based Screening for Rifampicin Susceptibility in the Emerging Mutation Hotspot at rpoB Codon 491.","authors":"Nicole A Malofsky, Swayashreyee B Dhungel, Megan E Pask, Frederick R Haselton","doi":"10.1021/acsinfecdis.5c00150","DOIUrl":"10.1021/acsinfecdis.5c00150","url":null,"abstract":"Based on sequencing data, mutations at rpoB codon 491 ofMycobacterium tuberculosisare associated with rifampicin resistance, but current commercial and WHO-endorsed genotypic tests fail to detect them. As a result, resistant infections go untreated, driving transmission and multidrug resistance. A real-time PCR assay by André et al. specifically screens for I491F but omits other codon 491 mutations. To address this gap, a single-sample screening method using asymmetric PCR followed by melt analysis was developed for the three sequence-identified variants, I491F/N/M. Each sample contained a melt probe matching the susceptible sequence, which, after asymmetric PCR spanning codon 491, hybridized with the excess strand to form a duplex. The duplex's melt temperature (Tm) was then measured. To enable single-sample classification, each reaction also included double-stranded L-DNA identical to the probe and wild-type PCR product duplex. Susceptibility was determined by the within-sample Tm difference between the probe-product and L-DNA duplexes. The approach was evaluated and compared to the André assay across two calibrated PCR instruments using synthetic rpoB wild-type and variant sequences. As expected, the André assay distinguished wild-type from I491F samples but misclassified I491N and I491M samples based on multisample Tm comparison. In contrast, our single-sample classification strategy used within-sample Tm differences, classifying samples as rifampicin-susceptible when the within-sample Tm difference was less than 0.83 °C. With this approach, the method achieved 100% sensitivity and 100% specificity across both PCR instruments. Although demonstrated for rpoB codon 491, this assay design is readily adaptable to any other sequence-identified, clinically significant mutation hotspot.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"1934-1943"},"PeriodicalIF":4.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315503","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}

引用次数: 0

The Mycomembrane Differentially and Heterogeneously Restricts Antibiotic Permeation. 菌丝膜的差异性和异质性限制了抗生素的渗透。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-11 Epub Date: 2025-06-05 DOI: 10.1021/acsinfecdis.4c01062

Irene Lepori, Kiserian Jackson, Zichen Liu, Mahendra D Chordia, Mitchell Wong, Sylvia L Rivera, Marta Roncetti, Laura Poliseno, Joel S Freundlich, Marcos M Pires, M Sloan Siegrist

{"title":"The Mycomembrane Differentially and Heterogeneously Restricts Antibiotic Permeation.","authors":"Irene Lepori, Kiserian Jackson, Zichen Liu, Mahendra D Chordia, Mitchell Wong, Sylvia L Rivera, Marta Roncetti, Laura Poliseno, Joel S Freundlich, Marcos M Pires, M Sloan Siegrist","doi":"10.1021/acsinfecdis.4c01062","DOIUrl":"10.1021/acsinfecdis.4c01062","url":null,"abstract":"The recalcitrance of Mycobacterium tuberculosis to antibiotic treatment has been broadly attributed to the impermeability of the organism's outer mycomembrane. However, the studies that support this inference have been indirect or reliant on bulk population measurements. We previously developed the Peptidoglycan Accessibility Click-Mediated AssessmeNt (PAC-MAN) method to covalently trap azide-modified small molecules in the peptidoglycan cell wall of live mycobacteria after they have traversed the mycomembrane. Using PAC-MAN, we now show that the mycomembrane differentially restricts access to fluorophores and antibiotic derivatives. Mycomembranes of both M. tuberculosis and the model organism Mycobacterium smegmatis discriminate between divergent classes of antibiotics as well as between antibiotics within a single family, the fluoroquinolones. By analyzing subpopulations of M. tuberculosis and M. smegmatis, we also found that some fluorophores and vancomycin are heterogeneously restricted by the mycomembrane. Our data indicate that the mycomembrane is a molecule- and cell-specific barrier to antibiotic permeation.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"1893-1906"},"PeriodicalIF":4.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232622","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

An Engineered Prodrug Selectively Suppresses β-Lactam-Resistant Bacteria in a Mixed Microbial Setting. 工程前药在混合微生物环境中选择性抑制β-内酰胺耐药细菌。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-11 Epub Date: 2025-06-12 DOI: 10.1021/acsinfecdis.5c00179

Addison M Duda, Helena R Ma, César A Villalobos, Sophia A Kuhn, Sarah S Angle, Katherine He, Abigail C Jackson, Christine M Suh, Elena A Puccio, Deverick J Anderson, Vance G Fowler, Lingchong You, Katherine J Franz

{"title":"An Engineered Prodrug Selectively Suppresses β-Lactam-Resistant Bacteria in a Mixed Microbial Setting.","authors":"Addison M Duda, Helena R Ma, César A Villalobos, Sophia A Kuhn, Sarah S Angle, Katherine He, Abigail C Jackson, Christine M Suh, Elena A Puccio, Deverick J Anderson, Vance G Fowler, Lingchong You, Katherine J Franz","doi":"10.1021/acsinfecdis.5c00179","DOIUrl":"10.1021/acsinfecdis.5c00179","url":null,"abstract":"The rise of β-lactam resistance necessitates new strategies to combat bacterial infections. We purposefully engineered the β-lactam prodrug AcephPT to exploit β-lactamase activity to selectively suppress resistant bacteria producing extended-spectrum-β-lactamases (ESBLs). Selective targeting of resistant bacteria requires avoiding interaction with penicillin-binding proteins, the conventional targets of β-lactam antibiotics, while maintaining recognition by ESBLs to activate AcephPT only in resistant cells. We show that AcephPT selectively suppresses Gram-negative ESBL-producing bacteria in clonal populations and in mixed microbial cultures, with effective selectivity for both lab strains and clinical isolates expressing ESBLs. Time-course NMR experiments confirm the hydrolytic activation of AcephPT exclusively by ESBL-producing bacteria. In mixed microbial cultures, AcephPT suppresses proliferation of an ESBL-producing strain while sustaining growth of β-lactamase-nonproducing bacteria, highlighting its potential to combat β-lactam resistance while promoting antimicrobial stewardship.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"1956-1967"},"PeriodicalIF":4.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273651","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

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-11

Huan Hu, Qiang Deng, Cheng Guo, Qin Wu and Qianlin Li*,

引用次数: 0

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-07-11

Di Liu, Xiaodan Li, Zhaoran Zhang, Ziyi Zhang, Hui Wang, Wenqi Dong, Xiangru Wang, Huanchun Chen, Chenchen Wang* and Chen Tan*,

引用次数: 0