ACS Infectious Diseases最新文献

Bosutinib Restores the Sensitivity of Colistin against Mcr-1-Positive E. coli. 博舒替尼恢复粘菌素对mcr -1阳性大肠杆菌的敏感性。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-06-27 DOI: 10.1021/acsinfecdis.5c00277

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

{"title":"Bosutinib Restores the Sensitivity of Colistin against Mcr-1-Positive E. coli.","authors":"Di Liu, Xiaodan Li, Zhaoran Zhang, Ziyi Zhang, Hui Wang, Wenqi Dong, Xiangru Wang, Huanchun Chen, Chenchen Wang, Chen Tan","doi":"10.1021/acsinfecdis.5c00277","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00277","url":null,"abstract":"Plasmid-mediated transmission of the mcr-1 gene significantly impairs the antimicrobial activity of colistin, limiting clinical therapeutic options. In this study, we evaluated the potential of bosutinib in restoring the susceptibility of colistin to mcr-1-positive drug-resistant Escherichia coli using a \"drug repurposing\" strategy and explored its mechanism of action to develop a new combination therapy regimen. We found that bosutinib combined with colistin significantly restored the susceptibility of mcr-1-positive E. coli to colistin and showed strong bactericidal and antibiofilm activities, confirmed by drug sensitivity assays, viable bacterial counts, and biofilm assays. Meanwhile, membrane permeability assay, reactive oxygen species (ROS) measurement, molecular docking, and SPR analysis showed that bosutinib could enhance bacterial membrane permeability, increase ROS accumulation, and directly bind to the MCR-1 protein, disrupting its resistance mechanism. Furthermore, in an infected animal model, bosutinib combined with colistin significantly increased the survival and reduced the bacterial load in tissues, confirming its in vivo antimicrobial efficacy. In conclusion, the present study reveals that bosutinib restores the antimicrobial activity of colistin through dual mechanisms: membrane permeability enhancement and direct targeting of the MCR-1 protein. Indeed, the discovery of bosutinib not only expands the application of tyrosine kinase inhibitor analogues in the field of anti-infective drugs but also provides a potentially new alternative for the clinical treatment of MCR-1-positive bacterial infections.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504117","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

Pathogenic Features, Experimental Models, and Molecular Tools of Human Fungal Pathogens: Who's on WHO's Radar? 人类真菌病原体的病原特征、实验模型和分子工具：谁在世卫组织的雷达上？

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-06-22 DOI: 10.1021/acsinfecdis.5c00081

Aswathy Narayanan, Amrutha Ambily Shaji, Dileep Pullepu, Joyee Bhattacharya, Kaustuv Sanyal

引用次数: 0

A High-Affinity and Potently Neutralized Nanobody against Zika Virus. 一种抗寨卡病毒的高亲和力和高效中和纳米体。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-06-22 DOI: 10.1021/acsinfecdis.5c00205

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

引用次数: 0

Playing Telephone: How Secondary Messengers Influence Host-Pathogen Interactions in Tuberculosis. 玩电话：次级信使如何影响肺结核的宿主-病原体相互作用。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-06-20 DOI: 10.1021/acsinfecdis.5c00077

Srivathsa Shankar Kurpad, Neeraj Dhar

{"title":"Playing Telephone: How Secondary Messengers Influence Host-Pathogen Interactions in Tuberculosis.","authors":"Srivathsa Shankar Kurpad, Neeraj Dhar","doi":"10.1021/acsinfecdis.5c00077","DOIUrl":"10.1021/acsinfecdis.5c00077","url":null,"abstract":"Secondary messengers are small, diffusible signaling molecules that transmit information from environmental cues detected at the cell surface by extracellular signaling molecules (primary messengers) to effector proteins, thereby enabling an appropriate cellular response. These molecules include cyclic nucleotides, alarmones, and lipid-derived metabolites and are ubiquitous regulators, influencing processes such as growth, metabolism, and neurotransmission in mammalian cells, as well as chemotaxis, biofilm formation, and metabolism in prokaryotes. Mycobacterium tuberculosis encodes an extensive array of genes dedicated to the synthesis and degradation of a diverse range of secondary messenger molecules. Given its highly intricate intracellular lifestyle and its ability to endure and persist in hostile and fluctuating environments, there is significant potential for crosstalk between host and bacterial secondary messengers. M. tuberculosis has likely co-opted these signaling processes within the host cell to facilitate its own pathogenesis and virulence. Recent studies have begun to elucidate the complex and multifaceted roles played by some of these secondary messengers, highlighting their capacity to regulate mycobacterial physiology while simultaneously modulating host immune responses. This review summarizes the current understanding of secondary messenger signaling in M. tuberculosis and explores how this knowledge is being leveraged to develop improved vaccines and therapeutic strategies.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332050","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

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 : 2025-06-17 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":"https://doi.org/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":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SARS-CoV-2 Evolved Variants Bind to Sialylated Gangliosides and Are Inhibited by a Tetravalent Sialo-Glycocluster. SARS-CoV-2进化变体与唾液化神经节苷结合，并被四价唾液糖簇抑制。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-06-17 DOI: 10.1021/acsinfecdis.5c00143

Geetanjali Negi, Vinay Kumar Pandey, Poojitha Sai Potharaju, Manoj K Jaiswal, Krishnan Harinivas Harshan, Vinod Kumar Tiwari, Nagma Parveen

{"title":"SARS-CoV-2 Evolved Variants Bind to Sialylated Gangliosides and Are Inhibited by a Tetravalent Sialo-Glycocluster.","authors":"Geetanjali Negi, Vinay Kumar Pandey, Poojitha Sai Potharaju, Manoj K Jaiswal, Krishnan Harinivas Harshan, Vinod Kumar Tiwari, Nagma Parveen","doi":"10.1021/acsinfecdis.5c00143","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00143","url":null,"abstract":"The altered tropism and infection severity of the evolved SARS-CoV-2 variants indicate engagement of attachment factors other than the ACE2 receptor for the cellular attachment and entry of the virus. In this work, we report the binding of Omicron, Delta, and B.1.1.8 (A2a type) variants to gangliosides (GD1a, GM3, GM1) with terminal sialic acid (SA). The binding kinetics of intact virus particles to these ganglioside-embedded lipid membranes reveal that the affinity of Omicron for GD1a (two SA residues) is the highest, and the lowest affinity is that of B.1.1.8 for GM1 (one SA at the branched chain). Our TIRF imaging data confirm that SA and acetylated SA can inhibit the virus attachment to the bilayers but at millimolar concentration. We evaluated tetravalent glycoclusters, i.e., sialo-porphyrin, galactose-porphyrin, and glucose-porphyrin, as multivalent inhibitors of SARS-CoV-2. Our results show that membrane attachment of the variants is blocked by the micromolar concentration of sialo-porphyrin. Even the glycocluster effectively inhibits cellular infection caused by the variants.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315502","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

Synthesis and Multidisciplinary Preclinical Investigations of Ferrocenyl, Ruthenocenyl, and Benzyl Derivatives of Thiabendazole as New Drug Candidates against Soil-Transmitted Helminth Infections. 噻苯达唑二茂铁、鲁thenenyl和苯基衍生物的合成及多学科临床前研究

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-06-16 DOI: 10.1021/acsinfecdis.5c00340

Tanja Karpstein, Apollonia Kalamatianou, Sarah Keller, Philipp Späne, Cécile Häberli, Alex Odermatt, Olivier Blacque, Kevin Cariou, Gilles Gasser, Jennifer Keiser

{"title":"Synthesis and Multidisciplinary Preclinical Investigations of Ferrocenyl, Ruthenocenyl, and Benzyl Derivatives of Thiabendazole as New Drug Candidates against Soil-Transmitted Helminth Infections.","authors":"Tanja Karpstein, Apollonia Kalamatianou, Sarah Keller, Philipp Späne, Cécile Häberli, Alex Odermatt, Olivier Blacque, Kevin Cariou, Gilles Gasser, Jennifer Keiser","doi":"10.1021/acsinfecdis.5c00340","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00340","url":null,"abstract":"An estimated 1.5 billion people worldwide are infected with at least one parasitic nematode species classified as soil-transmitted helminths (STHs). The recommended control strategy is to reduce morbidity using a single oral dose of the benzimidazole drugs, albendazole and mebendazole. The extensive use of benzimidazoles over the last decades has increased the risk of emerging drug resistance. Additional drawbacks, such as insufficient drug efficacy, particularly against hookworm and whipworm infections, highlight the urgent need for new and improved treatment options. In this work, we present the synthesis, characterization, and biological evaluation of four novel (organometallic and benzyl) derivatives (1-4) of the broad-spectrum anthelmintic thiabendazole. The in vitro evaluation of the derivatives on different life stages of five nematode species and Schistosoma mansoni demonstrated that the activity profile of thiabendazole could be extended. The highest activity in vitro was observed with benzyl derivative 2 against adult Trichuris muris (80% activity at 100 μM, after 72 h) compared to the parent compound thiabendazole (15% activity). Both ferrocenyl (1 and 3) and ruthenocenyl (4) derivatives demonstrated notable efficacy against adult S. mansoni at 50 μM. No toxicity was seen using the hepatocyte-derived carcinoma cell line HUH7 and the human neuroblastoma cell line SH-SY5Y. In vivo studies in the Heligmosomoides polygyrus mouse model revealed worm burden reductions of 61-78% following single oral doses of 100-200 mg/kg. Future derivatization efforts could focus on two separate targets: one aimed at enhancing STH activity and a second series pursuing the antischistosomal activity.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309244","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

Salmonella Typhimurium Infection and Excretion Following Sublethal Exposure to Insecticidal Bait in the German Cockroach Vector. 德国蜚蠊亚致死毒饵暴露后鼠伤寒沙门菌感染及排泄。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-06-15 DOI: 10.1021/acsinfecdis.5c00184

Landen Van Hulzen, Jose E Pietri

{"title":"Salmonella Typhimurium Infection and Excretion Following Sublethal Exposure to Insecticidal Bait in the German Cockroach Vector.","authors":"Landen Van Hulzen, Jose E Pietri","doi":"10.1021/acsinfecdis.5c00184","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00184","url":null,"abstract":"The German cockroach, Blattella germanica, is a widespread indoor pest and a vector of enteric human pathogens, including Salmonella enterica serovar Typhimurium (S. Typhimurium). Insecticidal baits are the most commonly used tools to control these cockroaches in built environments. Sublethal exposure to insecticidal baits has been a major driver of adaptive evolution, leading to physiological resistance to insecticides and behavioral aversion to glucose in some cockroach populations. Here, we conducted the first study investigating the effects of sublethal bait exposure on human pathogen biology in B. germanica. Our results show that a sublethal exposure to bait containing the common insecticide indoxacarb can increase susceptibility to subsequent infection by ingested S. Typhimurium in surviving cockroaches within the same generation. Interestingly, increased susceptibility to infection after sublethal bait exposure was cockroach strain dependent and did not increase the rate of shedding of the pathogen in excreta. These findings establish for the first time a potential link between a common anthropogenic intervention used to control this prevalent indoor pest and its capacity to maintain pathogens. In doing so, our work reveals a possible unintended consequence of failed pest control efforts. That is, some cockroach populations may become inadvertently more adept at maintaining pathogens due to sublethal exposure to baits stemming from existing insecticide resistance. Additional studies should further investigate this phenomenon to determine its extent and impact.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300538","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 : 2025-06-13

Calvin Joel Gordon, Simon Maximus Walker, Julia Christine LeCher, Franck Amblard, Raymond Felix Schinazi and Matthias Götte*,

引用次数: 0

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2025-06-13

Varsha Saini, Sayed M. Safwan, Devashish Mehta, Eric Evan Das and Avinash Bajaj*,

引用次数: 0