npj antimicrobials and resistance最新文献

Heteroresistance in Enterobacter cloacae complex caused by variation in transient gene amplification events.

npj antimicrobials and resistance Pub Date : 2025-02-22 DOI: 10.1038/s44259-025-00082-7

Johannes Kupke, Julian Brombach, Yuwen Fang, Silver A Wolf, Lakshmipriya Thrukonda, Fereshteh Ghazisaeedi, Benno Kuropka, Dennis Hanke, Torsten Semmler, Niclas Nordholt, Frank Schreiber, Karsten Tedin, Antina Lübke-Becker, Ulrich K Steiner, Marcus Fulde

{"title":"Heteroresistance in Enterobacter cloacae complex caused by variation in transient gene amplification events.","authors":"Johannes Kupke, Julian Brombach, Yuwen Fang, Silver A Wolf, Lakshmipriya Thrukonda, Fereshteh Ghazisaeedi, Benno Kuropka, Dennis Hanke, Torsten Semmler, Niclas Nordholt, Frank Schreiber, Karsten Tedin, Antina Lübke-Becker, Ulrich K Steiner, Marcus Fulde","doi":"10.1038/s44259-025-00082-7","DOIUrl":"10.1038/s44259-025-00082-7","url":null,"abstract":"Heteroresistance (HR) in bacteria describes a subpopulational phenomenon of antibiotic resistant cells of a generally susceptible population. Here, we investigated the molecular mechanisms and phenotypic characteristics underlying HR to ceftazidime (CAZ) in a clinical Enterobacter cloacae complex strain (ECC). We identified a plasmid-borne gene duplication-amplification (GDA) event of a region harbouring an ampC gene encoding a β-lactamase blaDHA-1 as the key determinant of HR. Individual colonies exhibited variations in the copy number of the genes resulting in resistance level variation which correlated with growth onset (lag times) and growth rates in the presence of CAZ. GDA copy number heterogeneity occurred within single resistant colonies, demonstrating heterogeneity of GDA on the single-cell level. The interdependence between GDA, lag time and antibiotic treatment and the strong plasticity underlying HR underlines the high risk for misdetection of antimicrobial HR and subsequent treatment failure.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rethinking the words hostspot reservoir and pristine in the environmental dimensions of antimicrobial resistance.

npj antimicrobials and resistance Pub Date : 2025-02-21 DOI: 10.1038/s44259-025-00080-9

Richard Helliwell, Isabel Ewin, Alexander D Williams, Diane T Levine, Andrew C Singer, Sujatha Raman, Carol Morris, Dov J Stekel

引用次数: 0

Flash optimization of drug combinations for Acinetobacter baumannii with IDentif.AI-AMR.

npj antimicrobials and resistance Pub Date : 2025-02-21 DOI: 10.1038/s44259-025-00079-2

Kui You, Nurhidayah Binte Mohamed Yazid, Li Ming Chong, Lissa Hooi, Peter Wang, Isaiah Zhuang, Stephen Chua, Ethan Lim, Alrick Zi Xin Kok, Kalisvar Marimuthu, Shawn Vasoo, Oon Tek Ng, Conrad E Z Chan, Edward Kai-Hua Chow, Dean Ho

{"title":"Flash optimization of drug combinations for Acinetobacter baumannii with IDentif.AI-AMR.","authors":"Kui You, Nurhidayah Binte Mohamed Yazid, Li Ming Chong, Lissa Hooi, Peter Wang, Isaiah Zhuang, Stephen Chua, Ethan Lim, Alrick Zi Xin Kok, Kalisvar Marimuthu, Shawn Vasoo, Oon Tek Ng, Conrad E Z Chan, Edward Kai-Hua Chow, Dean Ho","doi":"10.1038/s44259-025-00079-2","DOIUrl":"10.1038/s44259-025-00079-2","url":null,"abstract":"Antimicrobial resistance (AMR) is an emerging threat to global public health. Specifically, Acinetobacter baumannii (A. baumannii), one of the main pathogens driving the rise of nosocomial infections, is a Gram-negative bacillus that displays intrinsic resistance mechanisms and can also develop resistance by acquiring AMR genes from other bacteria. More importantly, it is resistant to nearly 90% of standard of care (SOC) antimicrobial treatments, resulting in unsatisfactory clinical outcomes and a high infection-associated mortality rate of over 30%. Currently, there is a growing challenge to sustainably develop novel antimicrobials in this ever-expanding arms race against AMR. Therefore, a sustainable workflow that properly manages healthcare resources to ultra-rapidly design optimal drug combinations for effective treatment is needed. In this study, the IDentif.AI-AMR platform was harnessed to pinpoint effective regimens against four A. baumannii clinical isolates from a pool of nine US FDA-approved drugs. Notably, IDentif.AI-pinpointed ampicillin-sulbactam/cefiderocol and cefiderocol/polymyxin B/rifampicin combinations were able to achieve 93.89 ± 5.95% and 92.23 ± 11.89% inhibition against the bacteria, respectively, and they may diversify the reservoir of treatment options for the indication. In addition, polymyxin B in combination with rifampicin exhibited broadly applicable efficacy and strong synergy across all tested clinical isolates, representing a potential treatment strategy for A. baumannii. IDentif.AI-pinpointed combinations may potentially serve as alternative treatment strategies for A. baumannii.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473250","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

An Australian perspective on clinical, economic and regulatory considerations in emerging nanoparticle therapies for infections.

npj antimicrobials and resistance Pub Date : 2025-02-18 DOI: 10.1038/s44259-024-00070-3

Benjamin W Muir, Jennifer A E Payne, Jennifer H Martin, Riley O' Shea, Sarigama Rajesh, Lewis D Blackman, Hsin-Hui Shen, Chad Heazlewood, Vipul Bansal, Branwen Morgan

引用次数: 0

Genomic survey of multidrug resistant Salmonella enterica serovar Minnesota clones in chicken products.

npj antimicrobials and resistance Pub Date : 2025-02-11 DOI: 10.1038/s44259-025-00077-4

Jiayi Huang, Khaloud O Alzahrani, Ge Zhou, Shahad A Alsalman, Amani T Alsufyani, Nourah M Alotaibi, Saleh I Al-Akeel, Abdullah A Alajlan, Lenah E Mukhtar, Ayidh M Almansour, Fahad M Al-Reshoodi, Malfi S Al Rashidy, Shaykhah Alhussain, Afnan Althobaiti, Manal Almusa, Talah Almadi, Nouf Almutairi, Abdulrahman Alzauhair, Meshari A Alhadlaq, Elaf Alshodokhi, Ashwag Alhamed, Abdulmohsen L AlHarbi, Manuel Banzhaf, Mathew Milner, Mohammad AlArawi, Sulaiman M Alajel, Danesh Moradigaravand

{"title":"Genomic survey of multidrug resistant Salmonella enterica serovar Minnesota clones in chicken products.","authors":"Jiayi Huang, Khaloud O Alzahrani, Ge Zhou, Shahad A Alsalman, Amani T Alsufyani, Nourah M Alotaibi, Saleh I Al-Akeel, Abdullah A Alajlan, Lenah E Mukhtar, Ayidh M Almansour, Fahad M Al-Reshoodi, Malfi S Al Rashidy, Shaykhah Alhussain, Afnan Althobaiti, Manal Almusa, Talah Almadi, Nouf Almutairi, Abdulrahman Alzauhair, Meshari A Alhadlaq, Elaf Alshodokhi, Ashwag Alhamed, Abdulmohsen L AlHarbi, Manuel Banzhaf, Mathew Milner, Mohammad AlArawi, Sulaiman M Alajel, Danesh Moradigaravand","doi":"10.1038/s44259-025-00077-4","DOIUrl":"10.1038/s44259-025-00077-4","url":null,"abstract":"Salmonella enterica serovar Minnesota (S. Minnesota) is an emerging serovar that persists within poultry supply chains, potentially causing outbreaks in humans. Understanding its population genomics is crucial for designing preventive measures. We performed a genomic surveillance study of S. Minnesota by analyzing 259 isolates from poultry in Saudi Arabia. Whole-genome sequencing data for these isolates were analyzed to characterize emerging clones and the genetic factors underlying antimicrobial resistance and virulence. We compared the isolates to all available global genomes of S. Minnesota. Our results revealed the emergence of four clones, three of which were mixed with global strains. These clones exhibited higher levels of antimicrobial resistance and virulence due to the acquisition of multiple plasmids, particularly IncC plasmids, carrying resistance and virulence genes. IncC plasmids underwent genomic rearrangements, presenting diverse configurations of resistance genes. Our findings demonstrate the emergence and persistence of pathogenic and multidrug-resistant S. Minnesota clones.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401179","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

Genomic analysis of antimicrobial resistant Escherichia coli isolated from manure and manured agricultural grasslands.

npj antimicrobials and resistance Pub Date : 2025-02-03 DOI: 10.1038/s44259-025-00081-8

C Tyrrell, C M Burgess, F P Brennan, D Münzenmaier, D Drissner, R J Leigh, F Walsh

{"title":"Genomic analysis of antimicrobial resistant Escherichia coli isolated from manure and manured agricultural grasslands.","authors":"C Tyrrell, C M Burgess, F P Brennan, D Münzenmaier, D Drissner, R J Leigh, F Walsh","doi":"10.1038/s44259-025-00081-8","DOIUrl":"10.1038/s44259-025-00081-8","url":null,"abstract":"Antimicrobial resistance (AMR) is a multifactorial issue involving an intertwining relationship between animals, humans and the environment. The environment can harbour Escherichia coli that are pathogenic or commensal. Escherichia coli is used as an indicator of environmental faecal contamination. Through culture dependent approaches this study identified 46 E. coli isolates in porcine and bovine manure, non-manured and manured soil, and manured grass. The grass isolation highlights grass as an environmental reservoir for E. coli. We also identified a diverse plasmidome with 23 different plasmid replicon types. The E. coli isolates were phenotypically antimicrobial resistant, predominantly multidrug resistant. Whole genome sequencing identified 31 antimicrobial resistance genes, and mutations in the gyrA, parC, and parE genes, conferring fluoroquinolone resistance. This study demonstrates grass as an understudied environmental niche of AMR E. coli, which directly links the environment to the grass grazing animal and vice-versa via the circular economy of manure application.","PeriodicalId":520007,"journal":{"name":"npj antimicrobials and resistance","volume":"3 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124257","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

Epidemiology, mechanisms, and clinical impact of bacterial heteroresistance.

npj antimicrobials and resistance Pub Date : 2025-01-28 DOI: 10.1038/s44259-025-00076-5

Linna Xu, Xiaofen Mo, Hui Zhang, Fen Wan, Qixia Luo, Yonghong Xiao

引用次数: 0

Targeting Acinetobacter baumannii resistance-nodulation-division efflux pump transcriptional regulators to combat antimicrobial resistance.

npj antimicrobials and resistance Pub Date : 2025-01-25 DOI: 10.1038/s44259-024-00074-z

Ruwani L Wimalasekara, Dawn White, Ayush Kumar

引用次数: 0

A historical perspective on the multifunctional outer membrane channel protein TolC in Escherichia coli.

npj antimicrobials and resistance Pub Date : 2025-01-25 DOI: 10.1038/s44259-025-00078-3

Mallory Wright, Mandeep Kaur, Laura K Thompson, Georgina Cox

引用次数: 0

The genus Nocardia as a source of new antimicrobials.

npj antimicrobials and resistance Pub Date : 2025-01-25 DOI: 10.1038/s44259-025-00075-6

Napawit Nonthakaew, Liam K R Sharkey, Sacha J Pidot

引用次数: 0