{"title":"Metabolic state-driven nutrient-based approach to combat bacterial antibiotic resistance.","authors":"Bo Peng, Hui Li, Xuan-Xian Peng","doi":"10.1038/s44259-025-00092-5","DOIUrl":"10.1038/s44259-025-00092-5","url":null,"abstract":"<p><p>To combat antibiotic resistance, one innovative approach, known as the metabolic state-driven approach, exploits the fact that exogenous nutrient metabolites can stimulate uptake of antibiotics. The most effective nutrient metabolites are identified by comparing metabolic states between antibiotic-sensitive and -resistant bacteria. When bacteria are exposed to the specific nutrient metabolites, they undergo a form of metabolic reprogramming. This review summarizes the recent progress on the metabolic state-driven approach.</p>","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789513","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}
Rebecca E McHugh, Liam M Rooney, David R Mark, Kabo R Wale, Megan Clapperton, Gail McConnell, Paul A Hoskisson, Gillian R Douce, Andrew J Roe
{"title":"Evaluating the protective effects of Aurodox in a murine model of Shiga toxin-producing Escherichia coli.","authors":"Rebecca E McHugh, Liam M Rooney, David R Mark, Kabo R Wale, Megan Clapperton, Gail McConnell, Paul A Hoskisson, Gillian R Douce, Andrew J Roe","doi":"10.1038/s44259-025-00094-3","DOIUrl":"10.1038/s44259-025-00094-3","url":null,"abstract":"<p><p>Shiga Toxin-Producing E. coli (STEC) are a group of acute small intestine pathogens responsible for foodborne outbreaks of bloody diarrhoea. The expression of Shiga toxins (Stx) carried by STEC can initiate Haemolytic Uremic Syndrome (HUS), a major cause of acute renal failure in children. Here, we investigate the anti-virulence potential of Aurodox - a natural product of Streptomyces goldiniensis. Previously, we have shown that Aurodox downregulates the expression of the T3SS, inhibiting epithelial cell colonisation in vitro. Here, we use the Citrobacter rodentium DBS770 (Cr Stx2<sub>dact</sub>) model of STEC infection to demonstrate that Aurodox protects mice against Citrobacter rodentium-associated colonic hyperplasia and Stx-mediated renal injury. Given antibiotic-associated dysbiosis of the gut is associated with inflammation and the emergence of opportunistic pathogens, we examined the effect of Aurodox on the faecal bacteriome. We show that although the microbial community is altered following Aurodox treatment, changes are distinct from those associated with traditional antibiotic therapies.</p>","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766228","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}
{"title":"Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery.","authors":"Victor Choi, Dario Carugo, Eleanor Stride","doi":"10.1038/s44259-025-00086-3","DOIUrl":"10.1038/s44259-025-00086-3","url":null,"abstract":"<p><p>Chronic infections represent a major clinical challenge due to the enhanced antimicrobial tolerance of biofilm-dwelling bacteria. To address this challenge, an ultrasound-responsive nanoscale drug delivery platform (nanodroplets) is presented in this work, loaded with four different antimicrobial agents, capable of simultaneous biofilm disruption and targeted antimicrobial delivery. When loaded, a robust protective effect against clinically-derived MRSA and ESBL Gram-positive and Gram-negative planktonic isolates was shown in vitro. Upon application of therapeutic ultrasound, an average 7.6-fold, 44.4-fold, and 25.5-fold reduction was observed in the antibiotic concentrations compared to free drug required to reach the MBC, MBEC and complete persister eradication levels, respectively. Nanodroplets substantially altered subcellular distribution of encapsulated antimicrobials, enhancing accumulation of antimicrobials by 11.1-fold within the biofilm-residing bacteria's cytoplasm compared to treatment with unencapsulated drugs. These findings illustrate the potential of this multifunctional platform to overcome the critical penetration and localization limitations of antimicrobials within biofilms, opening potential new avenues in the treatment of chronic clinical infections.</p>","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766229","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}
{"title":"Exploiting social traits for clinical applications in bacteria and viruses.","authors":"Ashleigh S Griffin, Asher Leeks","doi":"10.1038/s44259-025-00091-6","DOIUrl":"10.1038/s44259-025-00091-6","url":null,"abstract":"<p><p>Despite generating a great deal of interest in the form of review papers, progress in exploiting social dynamics for treatment strategies against bacterial infection has made limited progress since it was suggested twenty years ago. In contrast, anti-viral strategies based on social interactions are entering clinical trial stage. We explore possible reasons for this difference and highlight areas where the two fields of research may learn from one another.</p>","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744631","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}
Marlon I Diaz, Lauren N Cooper, John J Hanna, Alaina M Beauchamp, Tanvi A Ingle, Abdi D Wakene, Zachary Most, Trish Perl, Chaitanya Katterpalli, Tony Keller, Clark Walker, Christoph U Lehmann, Richard J Medford
{"title":"Integrating socioeconomic deprivation indices and electronic health record data to predict antimicrobial resistance.","authors":"Marlon I Diaz, Lauren N Cooper, John J Hanna, Alaina M Beauchamp, Tanvi A Ingle, Abdi D Wakene, Zachary Most, Trish Perl, Chaitanya Katterpalli, Tony Keller, Clark Walker, Christoph U Lehmann, Richard J Medford","doi":"10.1038/s44259-025-00090-7","DOIUrl":"https://doi.org/10.1038/s44259-025-00090-7","url":null,"abstract":"<p><p>We developed machine learning models to predict the presence of AMR organisms in blood cultures obtained at the first patient encounter, offering a new and inspiring direction for antimicrobial resistance management. Three supervised machine learning classifiers were used: penalized logistic regression, random forest, and XGBoost, which were used to classify five AMR organisms: ESBL, CRE, AmpC, MRSA, and VRE. The random forest and XGBoost models performed best, with AUC-ROC values of 0.70 and 92.9% negative predictive value, respectively. The multi-class random forest model's AUC-ROC values ranged from 0.80-0.95. Our models highlight how the combination of ADI and SVI increased the predictive power. This approach could reduce costs and mitigate the global public health threat posed by antibiotic-resistant infections. Machine learning techniques can predict antimicrobial-resistant infections in suspected cultures using patient data from EHRs, enabling clinicians to make targeted prescribing decisions and mitigate resistance development.</p>","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744634","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}
Autumn Arnold, Stewart McLellan, Jonathan M Stokes
{"title":"How AI can help us beat AMR.","authors":"Autumn Arnold, Stewart McLellan, Jonathan M Stokes","doi":"10.1038/s44259-025-00085-4","DOIUrl":"10.1038/s44259-025-00085-4","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) is an urgent public health threat. Advancements in artificial intelligence (AI) and increases in computational power have resulted in the adoption of AI for biological tasks. This review explores the application of AI in bacterial infection diagnostics, AMR surveillance, and antibiotic discovery. We summarize contemporary AI models applied to each of these domains, important considerations when applying AI across diverse tasks, and current limitations in the field.</p>","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627090","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}
Silvia T Cardona, A S M Zisanur Rahman, Julieta Novomisky Nechcoff
{"title":"Innovative perspectives on the discovery of small molecule antibiotics.","authors":"Silvia T Cardona, A S M Zisanur Rahman, Julieta Novomisky Nechcoff","doi":"10.1038/s44259-025-00089-0","DOIUrl":"10.1038/s44259-025-00089-0","url":null,"abstract":"<p><p>Antibiotics are essential to modern medicine, but multidrug-resistant (MDR) bacterial infections threaten their efficacy. Resistance evolution shortens antibiotic lifespans, limiting investment returns and slowing new approvals. Consequently, the WHO defines four innovation criteria: new chemical class, target, mode of action (MoA), and lack of cross-resistance. This review explores innovative discovery approaches, including AI-driven screening, metagenomics, and target-based strategies, to develop novel antibiotics that meet these criteria and combat MDR infections.</p>","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627149","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}
Madeline Mei, Isaac Estrada, Stephen P Diggle, Joanna B Goldberg
{"title":"R-pyocins as targeted antimicrobials against Pseudomonas aeruginosa.","authors":"Madeline Mei, Isaac Estrada, Stephen P Diggle, Joanna B Goldberg","doi":"10.1038/s44259-025-00088-1","DOIUrl":"10.1038/s44259-025-00088-1","url":null,"abstract":"<p><p>R-pyocins, bacteriocin-like proteins produced by Pseudomonas aeruginosa, present a promising alternative to phage therapy and/or adjunct to currently used antimicrobials in treating bacterial infections due to their targeted specificity, lack of replication, and stability. This review explores the structural, mechanistic, and therapeutic aspects of R-pyocins, including their potential for chronic infection management, and discusses recent advances in delivery methods, paving the way for novel antimicrobial applications in clinical settings.</p>","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532131","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}
Endrews Delbaje, Laís Pontes, Johanna Rhodes, Jacob Steenwyk, Ling Lu, Thaila F Dos Reis, Antonis Rokas, Gustavo H Goldman
{"title":"Aspergillus fumigatus mitogenomes and their influence on azole-resistant and -susceptible populations.","authors":"Endrews Delbaje, Laís Pontes, Johanna Rhodes, Jacob Steenwyk, Ling Lu, Thaila F Dos Reis, Antonis Rokas, Gustavo H Goldman","doi":"10.1038/s44259-025-00083-6","DOIUrl":"10.1038/s44259-025-00083-6","url":null,"abstract":"<p><p>The role of the fungal mitochondria goes far beyond energy metabolism. The genomes of 318 Aspergillus fumigatus clinical and environmental isolates from different geographic origins were analyzed aiming to study the mitochondrial sequences from populations sensitive and resistant to azoles. Our results show that A. fumigatus mitogenomic sequences are very conserved and only show variation in small intergenic regions and one intronic sequence in the cox3 gene. Furthermore, a genome-wide association analysis of accessory mitochondrial genes revealed potential mitochondria-based genotypes that may interact synergistically with the ergosterol biosynthesis pathway to confer the resistant phenotype. This includes a mutation in the AMID-like mitochondrial oxidoreductase (aifA, AFUA_3G01290) and the absence of the mitochondrial carrier protein (pet8, AFUA_8G01400). Deletion of these genes did not change the azole-susceptibility but increased the azole-persistence, suggesting mitochondrial genes could be involved in azole-persistence. Our work opens new hypotheses for the involvement of mitochondria in A. fumigatus azole-resistance.</p>","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525944","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}
Daniele Roberto Giacobbe, Cristina Marelli, Bianca La Manna, Donatella Padua, Alberto Malva, Sabrina Guastavino, Alessio Signori, Sara Mora, Nicola Rosso, Cristina Campi, Michele Piana, Ylenia Murgia, Mauro Giacomini, Matteo Bassetti
{"title":"Advantages and limitations of large language models for antibiotic prescribing and antimicrobial stewardship.","authors":"Daniele Roberto Giacobbe, Cristina Marelli, Bianca La Manna, Donatella Padua, Alberto Malva, Sabrina Guastavino, Alessio Signori, Sara Mora, Nicola Rosso, Cristina Campi, Michele Piana, Ylenia Murgia, Mauro Giacomini, Matteo Bassetti","doi":"10.1038/s44259-025-00084-5","DOIUrl":"10.1038/s44259-025-00084-5","url":null,"abstract":"<p><p>Antibiotic prescribing requires balancing optimal treatment for patients with reducing antimicrobial resistance. There is a lack of standardization in research on using large language models (LLMs) for supporting antibiotic prescribing, necessitating more efforts to identify biases and misinformation in their outputs. Educating future medical professionals on these aspects is crucial for ensuring the proper use of LLMs for supporting antibiotic prescribing, providing a deeper understanding of their strengths and limitations.</p>","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525985","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}