npj antimicrobials and resistance最新文献

Environmental hazards from pollution of antibiotics and resistance-driving chemicals in an urban river network from Malawi. 马拉维城市河网中抗生素和导致耐药性的化学品污染造成的环境危害。

npj antimicrobials and resistance Pub Date : 2025-10-09 DOI: 10.1038/s44259-025-00149-5

Derek Cocker, Taonga Mwapasa, Roman Grabic, Kateřina Grabicová, Andrea Vojs Staňová, Kondwani Chidziwisano, Adam P Roberts, Tracy Morse, Nicholas A Feasey, Andrew C Singer

{"title":"Environmental hazards from pollution of antibiotics and resistance-driving chemicals in an urban river network from Malawi.","authors":"Derek Cocker, Taonga Mwapasa, Roman Grabic, Kateřina Grabicová, Andrea Vojs Staňová, Kondwani Chidziwisano, Adam P Roberts, Tracy Morse, Nicholas A Feasey, Andrew C Singer","doi":"10.1038/s44259-025-00149-5","DOIUrl":"10.1038/s44259-025-00149-5","url":null,"abstract":"African communities have a high prevalence of antimicrobial-resistant bacterial carriage, alongside high levels of antibiotic usage and environmental pollution. Limited access to water, sanitation and hygiene infrastructure and wastewater treatment facilities enables the dissemination of resistant bacteria, antimicrobials and antibiotic resistance-driving chemicals (ARDCs) into local rivers. Few data exist quantifying the chemical drivers of antimicrobial resistance (AMR) in urban aquatic environments from African settings. In this longitudinal surveillance study, we investigated an urban river network in Blantyre, Malawi over a continuous 12-month period, identifying a broad-range of chemical pollutants, including antibiotics, common pharmaceuticals, agricultural and industrial chemicals and heavy metals. Antimicrobial concentrations were found at levels selective for AMR and ARDCs exhibited seasonal variations, indicating that deficient sanitation infrastructure and anthropogenic factors result in high antibiotic and ARDC levels entering the river systems, which serve as an important ecological niche for the acquisition, maintenance and transmission of AMR.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"85"},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Resistance of ERG24 sterol C-14 reductase to heterocyclic amine antifungals. ERG24甾醇C-14还原酶对杂环胺类抗真菌药物的抗性。

npj antimicrobials and resistance Pub Date : 2025-10-01 DOI: 10.1038/s44259-025-00155-7

Corinne J Arnold, Laetitia Chartrain, David M Lawson, James K M Brown

引用次数: 0

The butterfly effect: collateral damage and impacts of antimicrobial strategies on the oral microbiome. 蝴蝶效应：附带损害和抗菌策略对口腔微生物组的影响。

npj antimicrobials and resistance Pub Date : 2025-10-01 DOI: 10.1038/s44259-025-00156-6

Jason L Brown, William Johnston, Mark C Butcher, Mia Burleigh, Gordon Ramage

引用次数: 0

Relating antimicrobial use to wastewater resistance gene patterns via metagenomic analysis of two neighboring treatment plants circa the COVID-19 pandemic. 通过对COVID-19大流行期间两个相邻处理厂的宏基因组分析，将抗菌素使用与废水抗性基因模式联系起来。

npj antimicrobials and resistance Pub Date : 2025-09-30 DOI: 10.1038/s44259-025-00153-9

Ayella Maile-Moskowitz, Connor L Brown, Monjura Afrin Rumi, Nazifa Ahmed Moumi, Haniyyah Majeed, Carla V Finkielstein, Alessandro Ceci, Raul Gonzalez, Kang Xia, Lauren McDaniel, Anthony Baffoe-Bonnie, Jayasimha Rao, Liqing Zhang, Amy Pruden, Peter J Vikesland

{"title":"Relating antimicrobial use to wastewater resistance gene patterns via metagenomic analysis of two neighboring treatment plants circa the COVID-19 pandemic.","authors":"Ayella Maile-Moskowitz, Connor L Brown, Monjura Afrin Rumi, Nazifa Ahmed Moumi, Haniyyah Majeed, Carla V Finkielstein, Alessandro Ceci, Raul Gonzalez, Kang Xia, Lauren McDaniel, Anthony Baffoe-Bonnie, Jayasimha Rao, Liqing Zhang, Amy Pruden, Peter J Vikesland","doi":"10.1038/s44259-025-00153-9","DOIUrl":"10.1038/s44259-025-00153-9","url":null,"abstract":"Minimizing antimicrobial use is a recommended strategy to reduce the evolution and spread of antibiotic resistance; however, efficacy is elusive to measure. Wastewater-based surveillance provides a promising means to relate trends in microbial community antibiotic resistance profiles as a function of interventions and other factors. We examined influent sewage metagenomes for two neighboring wastewater treatment plants (WWTPs) serving a university and a nearby community. We compared antibiotic resistance gene (ARG) profiles as a function of diagnoses of COVID-19 and other illnesses, antibiotic use, antibiotic/antimicrobial and disinfectant/quaternary ammonium compound concentrations, and COVID-19-related behavioral shifts. Diversity and abundances of ARGs unique to the corresponding sewage were consistently higher for the community WWTP, but converged in 2022 when antibiotic prescriptions surged in the university zip code. Decreases in ARG diversity/abundance were not apparent during periods of decreased antibiotic usage, indicating that extended times may be required for wastewater ARG signals to attenuate following interventions.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"82"},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteomic and metabolomic responses of priority bacterial pathogens to subinhibitory concentration of antibiotics. 优先细菌病原体对抗生素亚抑制浓度的蛋白质组学和代谢组学反应。

npj antimicrobials and resistance Pub Date : 2025-09-16 DOI: 10.1038/s44259-025-00147-7

Monika Subanovic, Dean Frawley, Ciara Tierney, Trinidad Velasco-Torrijos, Fiona Walsh

{"title":"Proteomic and metabolomic responses of priority bacterial pathogens to subinhibitory concentration of antibiotics.","authors":"Monika Subanovic, Dean Frawley, Ciara Tierney, Trinidad Velasco-Torrijos, Fiona Walsh","doi":"10.1038/s44259-025-00147-7","DOIUrl":"10.1038/s44259-025-00147-7","url":null,"abstract":"This study employed a comprehensive proteomic and metabolomic analysis to characterize adaptive cellular mechanisms of priority pathogens-Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, and Staphylococcus aureus-under sub-inhibitory concentrations of antibiotics. Despite significant metabolomic perturbations, some pathogens had minimal or no significant changes in their proteome. Notably, trimethylamine metabolism was consistently altered across all species, suggesting its role in survival under antibiotic stress. Shared adaptive responses to chloramphenicol in S. aureus and E. faecium are related to translation, oxidative stress management, protein folding and stability, biofilm formation capacity, glycine metabolism and osmoprotection. Alterations in quaternary amines and trimethylamine metabolism suggest alternative nitrogen and carbon utilization pathways in response to antibiotic stress. In S. aureus, vancomycin suppressed metabolism, including D-alanine metabolism, and global regulators LytR, CodY and CcpA. These findings offer insights into early antimicrobial resistance mechanisms and highlight critical proteins and metabolites linked to antibiotic tolerance.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"80"},"PeriodicalIF":0.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Towards the integration of antibiotic resistance gene mobility into environmental surveillance and risk assessment. 将抗生素耐药基因迁移纳入环境监测和风险评估。

npj antimicrobials and resistance Pub Date : 2025-09-16 DOI: 10.1038/s44259-025-00154-8

Uli Klümper, Peiju Fang, Bing Li, Yu Xia, Dominic Frigon, Kerry A Hamilton, Hunter Quon, Thomas U Berendonk, Magali de la Cruz Barron

引用次数: 0

Communities of plasmids as strategies for antimicrobial resistance gene survival in wastewater treatment plant effluent. 质粒群落作为污水处理厂流出物中抗菌素耐药基因存活的策略。

npj antimicrobials and resistance Pub Date : 2025-09-09 DOI: 10.1038/s44259-025-00151-x

Cian Smyth, Robert J Leigh, Thi Thuy Do, Fiona Walsh

{"title":"Communities of plasmids as strategies for antimicrobial resistance gene survival in wastewater treatment plant effluent.","authors":"Cian Smyth, Robert J Leigh, Thi Thuy Do, Fiona Walsh","doi":"10.1038/s44259-025-00151-x","DOIUrl":"10.1038/s44259-025-00151-x","url":null,"abstract":"Plasmids facilitate antimicrobial resistance (AMR) gene spread via horizontal gene transfer, yet the mobility of genes in wastewater treatment plant (WWTP) resistomes remains unclear. We sequenced 173 circularised plasmids transferred from WWTP effluent into Escherichia coli and characterised their genetic content. Multiple multidrug-resistant plasmids were identified, with a significant number of mega-plasmids (>100 kb). Almost all plasmids detected existed with other plasmids i.e. as communities rather than lone entities. These plasmid communities enabled non-AMR plasmids to survive antimicrobial selection by co-existing with resistant partners. Our data demonstrates the highly variable nature of plasmids in addition to their capacity to carry mobile elements and genes within these highly variable regions. The impact of these variations on plasmid ecology, persistence, and transfer requires further investigation. Plasmid communities warrant exploration across biomes, as many non-resistant plasmids escape elimination by co-existing with AMR plasmids in the same bacterial host, representing a previously unrecognised survival strategy.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"78"},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Predicting drug inactivation by changes in bacterial growth dynamics. 通过细菌生长动力学的变化预测药物失活。

npj antimicrobials and resistance Pub Date : 2025-09-09 DOI: 10.1038/s44259-025-00152-w

Carmen Li, Serkan Sayin, Ethan Hau Chian Chang, Amir Mitchell

{"title":"Predicting drug inactivation by changes in bacterial growth dynamics.","authors":"Carmen Li, Serkan Sayin, Ethan Hau Chian Chang, Amir Mitchell","doi":"10.1038/s44259-025-00152-w","DOIUrl":"10.1038/s44259-025-00152-w","url":null,"abstract":"Studying how antibacterials operate at subinhibitory concentrations reveals how they impede normal growth. While previous works demonstrated drugs can impact multiple aspects of growth, such as prolonging the doubling time or reducing the maximal bacterial load, a systematic understanding of this phenomenon is lacking. It remains unknown if common principles dictate how drugs interfere with growth. We monitored growth curves across thirty-eight drugs, spanning multiple mechanisms of action in Escherichia coli to deconvolve their impact on the lag, growth rate, and carrying capacity and developed a mathematical framework to quantitatively compare their effects. We discovered that drugs induced considerably different inhibition phenotypes, which were independent from the drug's target. Functional assays of drug inactivation revealed that drug inactivation is a key shared factor underlying a lag-associated phenotype. Our work reveals that likely drug inactivation can be directly inferred from growth dynamics which is instrumental for rapidly identifying drug-inactivating bacteria.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"79"},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biosynthetic ε-poly-L-lysine for the treatment of extensively- and pan-drug-resistant Pseudomonas aeruginosa. 生物合成ε-聚l -赖氨酸治疗广泛耐药和泛耐药铜绿假单胞菌。

npj antimicrobials and resistance Pub Date : 2025-09-09 DOI: 10.1038/s44259-025-00142-y

Darren Shu Jeng Ting, Thet Tun Aung, Venkatesh Mayandi, Mercy Halleluyah Periayah, Eunice Tze Leng Goh, Mugil Muthu, Veluchamy Amutha Barathi, Jodhbir S Mehta, Donald Tiang Hwee Tan, Rajamani Lakshminarayanan

{"title":"Biosynthetic ε-poly-L-lysine for the treatment of extensively- and pan-drug-resistant Pseudomonas aeruginosa.","authors":"Darren Shu Jeng Ting, Thet Tun Aung, Venkatesh Mayandi, Mercy Halleluyah Periayah, Eunice Tze Leng Goh, Mugil Muthu, Veluchamy Amutha Barathi, Jodhbir S Mehta, Donald Tiang Hwee Tan, Rajamani Lakshminarayanan","doi":"10.1038/s44259-025-00142-y","DOIUrl":"10.1038/s44259-025-00142-y","url":null,"abstract":"Pseudomonas aeruginosa (PA) represents a major cause of antimicrobial resistance-related morbidity and mortality. The recent emergence of highly fatal infections, caused by carbapenem-resistant PA, has called for novel antimicrobial therapies and strategies. In this study, we highlight the therapeutic potential of ε-poly-L-lysine (εPL), an antimicrobial polymer for treating extensively-and pan-drug-resistant-PA. εPL displayed potent antimicrobial activity against all eight drug-resistant PA, including carbapenem- and polymyxin-resistant PA. It exhibited a low risk of AMR evolution, with no evidence of cross-resistance with polymyxin B (a last-line treatment for drug-resistant Gram-negative bacteria). We further demonstrated promising in vivo efficacy and safety of εPL against PA in a pre-clinical PA keratitis model, with comparable effects to topical levofloxacin (a gold standard treatment of infectious keratitis) in terms of clinical scoring, corneal health/thickness, and bacterial bioburden. In view of its broad-spectrum antimicrobial activity, low risk of AMR evolution and cross-resistance with existing last-line antibiotics, and general acceptance of safety when orally administered, εPL serves as a promising novel antimicrobial agent for further clinical development and translation to tackle antimicrobial resistance.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"77"},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetic and pharmacodynamic studies of injectable nocathiacin as a novel antibacterial agent. 注射用诺卡那星作为新型抗菌剂的药动学和药效学研究。

npj antimicrobials and resistance Pub Date : 2025-09-01 DOI: 10.1038/s44259-025-00148-6

Xisheng Xiong, Junjian Qian, Lang Wang, Jiawei Liu, Lulu Zhang, Kai Diao, Tao Tang, Xianliang Zhang, Xuri Wu, Yijun Chen

{"title":"Pharmacokinetic and pharmacodynamic studies of injectable nocathiacin as a novel antibacterial agent.","authors":"Xisheng Xiong, Junjian Qian, Lang Wang, Jiawei Liu, Lulu Zhang, Kai Diao, Tao Tang, Xianliang Zhang, Xuri Wu, Yijun Chen","doi":"10.1038/s44259-025-00148-6","DOIUrl":"10.1038/s44259-025-00148-6","url":null,"abstract":"The extreme hydrophobicity of nocathiacin, a potent thiopeptide antibiotic against multidrug-resistant (MDR) Gram-positive pathogens, has limited its clinical development. This study formulated an injectable lyophilized nocathiacin with enhanced solubility (12.59 mg/mL). In vitro testing against 1050 clinical isolates demonstrated exceptional potency (MIC50: 0.0078-0.0156 mg/L; 64-128-fold lower than vancomycin/linezolid) and bactericidal activity (MBC50 = 4-16 × MIC). Murine systemic and localized infection models showed superior efficacy (ED50: 0.64-1.96 mg/kg; ~3 log (CFU/g) reduction in lung/thigh at 2/8 mg/kg). PK/PD analysis in immunocompromised mice identified AUC0-24/MIC and %T > MIC as primary efficacy drivers (R2 ≥ 0.97), indicating time-dependent killing. Favorable PK in rats/monkeys included moderate half-lives (4.7-5.5 h), biliary-dominated excretion (26.01% parent drug), minimal renal clearance (<0.10%), and no CYP inhibition/induction or significant transporter interactions. These results support injectable nocathiacin as a promising clinical candidate for MDR Gram-positive infections.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"76"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0