Pub Date : 2025-02-17DOI: 10.1016/j.jgar.2025.02.006
Ronan F. O'Toole , Vitalie Covalciuc , Ana Cooke , Gaetan Thilliez , Emma K. Finlay , Kelvin W.C. Leong , Vanessa Farthing , Sebastiaan J. van Hal
Objective
High rates of resistance to vancomycin are now being reported among invasive isolates of Enterococcus faecium, a major cause of healthcare-associated infections globally. The objective of this study was to generate a better understanding of emerging vanA sequence types (ST) of the pathogen.
Methods
A temporal analysis of isolates collected from 2013 to 2020 at the Royal Prince Alfred Hospital, a large Australian hospital, was performed using genome sequencing. Relative frequencies of multi-locus ST, antibiotic resistance markers, and virulence genes were determined.
Results
ST1421 was the dominant vanA ST from 2014 to 2018. ST1424, which was not evident in the 2013 and 2014 isolates, emerged in 2016 and became the dominant vanA type in 2020 (65% of isolates). vanA ST80 was less common among the Royal Prince Alfred Hospital vanA isolates. Direct comparison of 120 genomes of each ST revealed significantly higher encoded resistance to aminocyclitols (e.g. spectinomycin) and folate-pathway antagonists (e.g. trimethoprim) in ST1421 and ST1424 compared to ST80. Furthermore, significantly higher carriage of enterococcal virulence genes ecbA (E. faecium collagen binding protein A) and hylEfm (glycosyl hydrolase) was found in ST1421 and ST1424 than in ST80.
Conclusions
Newer vanA ST ST1421 and ST1424 harboured several antibiotic resistance loci and virulence genes at significantly higher levels than those observed in ST80. Ongoing genomic surveillance is warranted for the detection of new variants of E. faecium and characterisation of their encoded resistance and virulence.
{"title":"Genomic characterisation of emerging Enterococcus faecium vanA types from 2013 to 2020 in an Australian public hospital","authors":"Ronan F. O'Toole , Vitalie Covalciuc , Ana Cooke , Gaetan Thilliez , Emma K. Finlay , Kelvin W.C. Leong , Vanessa Farthing , Sebastiaan J. van Hal","doi":"10.1016/j.jgar.2025.02.006","DOIUrl":"10.1016/j.jgar.2025.02.006","url":null,"abstract":"<div><h3>Objective</h3><div>High rates of resistance to vancomycin are now being reported among invasive isolates of <em>Enterococcus faecium</em>, a major cause of healthcare-associated infections globally. The objective of this study was to generate a better understanding of emerging <em>vanA</em> sequence types (ST) of the pathogen.</div></div><div><h3>Methods</h3><div>A temporal analysis of isolates collected from 2013 to 2020 at the Royal Prince Alfred Hospital, a large Australian hospital, was performed using genome sequencing. Relative frequencies of multi-locus ST, antibiotic resistance markers, and virulence genes were determined.</div></div><div><h3>Results</h3><div>ST1421 was the dominant <em>vanA</em> ST from 2014 to 2018. ST1424, which was not evident in the 2013 and 2014 isolates, emerged in 2016 and became the dominant <em>vanA</em> type in 2020 (65% of isolates). <em>vanA</em> ST80 was less common among the Royal Prince Alfred Hospital <em>vanA</em> isolates. Direct comparison of 120 genomes of each ST revealed significantly higher encoded resistance to aminocyclitols (e.g. spectinomycin) and folate-pathway antagonists (e.g. trimethoprim) in ST1421 and ST1424 compared to ST80. Furthermore, significantly higher carriage of enterococcal virulence genes <em>ecbA</em> (<em>E. faecium</em> collagen binding protein A) and <em>hylEfm</em> (glycosyl hydrolase) was found in ST1421 and ST1424 than in ST80.</div></div><div><h3>Conclusions</h3><div>Newer <em>vanA</em> ST ST1421 and ST1424 harboured several antibiotic resistance loci and virulence genes at significantly higher levels than those observed in ST80. Ongoing genomic surveillance is warranted for the detection of new variants of <em>E. faecium</em> and characterisation of their encoded resistance and virulence.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 42-50"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-13DOI: 10.1016/j.jgar.2025.02.002
Hannay Crystynah Almeida de Souza , Pedro Panzenhagen , Anamaria Mota Pereira dos Santos , Ana Beatriz Portes , Juliana Fidelis , Carlos Adam Conte-Junior
Antimicrobial resistance is a critical public health threat, compromising treatment effectiveness. The spread of resistant pathogens, facilitated by genetic variability and horizontal gene transfer, primarily through plasmids, poses significant challenges to health systems.
Objective
This review explores the potential of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology and Cas9 nucleases in combating antimicrobial resistance.
Methods
The literature review followed the PRISMA guidelines using PubMed, Embase, and Scopus databases until July 2023.
Results
The Enterobacterales family, particularly Escherichia coli, was the main focus. The resistance genes targeted were mainly associated with β-lactam antibiotics, specifically bla genes, and colistin resistance linked to the mcr-1 gene. Plasmid vectors have been the primary delivery method for the CRISPR-Cas9 system, with conjugative plasmids resensitizing bacterial strains to various antimicrobials. Other delivery methods included electroporation, phage-mediated delivery, and nanoparticles. The efficacy of the CRISPR-Cas9 system in resensitizing bacterial strains ranged from 4.7% to 100%.
Conclusions
Despite challenges in delivery strategies and clinical application, studies integrating nanotechnology present promising approaches to overcome these limitations. This review highlights new perspectives for the clinical use of CRISPR-Cas9 as a specific and efficient antimicrobial agent, potentially replacing traditional broad-spectrum antimicrobials in the future.
{"title":"Unravelling the advances of CRISPR-Cas9 as a precise antimicrobial therapy: A systematic review","authors":"Hannay Crystynah Almeida de Souza , Pedro Panzenhagen , Anamaria Mota Pereira dos Santos , Ana Beatriz Portes , Juliana Fidelis , Carlos Adam Conte-Junior","doi":"10.1016/j.jgar.2025.02.002","DOIUrl":"10.1016/j.jgar.2025.02.002","url":null,"abstract":"<div><div>Antimicrobial resistance is a critical public health threat, compromising treatment effectiveness. The spread of resistant pathogens, facilitated by genetic variability and horizontal gene transfer, primarily through plasmids, poses significant challenges to health systems.</div></div><div><h3>Objective</h3><div>This review explores the potential of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology and Cas9 nucleases in combating antimicrobial resistance.</div></div><div><h3>Methods</h3><div>The literature review followed the PRISMA guidelines using PubMed, Embase, and Scopus databases until July 2023.</div></div><div><h3>Results</h3><div>The <em>Enterobacterales</em> family, particularly <em>Escherichia coli</em>, was the main focus. The resistance genes targeted were mainly associated with β-lactam antibiotics, specifically <em>bla</em> genes, and colistin resistance linked to the <em>mcr-1</em> gene. Plasmid vectors have been the primary delivery method for the CRISPR-Cas9 system, with conjugative plasmids resensitizing bacterial strains to various antimicrobials. Other delivery methods included electroporation, phage-mediated delivery, and nanoparticles. The efficacy of the CRISPR-Cas9 system in resensitizing bacterial strains ranged from 4.7% to 100%.</div></div><div><h3>Conclusions</h3><div>Despite challenges in delivery strategies and clinical application, studies integrating nanotechnology present promising approaches to overcome these limitations. This review highlights new perspectives for the clinical use of CRISPR-Cas9 as a specific and efficient antimicrobial agent, potentially replacing traditional broad-spectrum antimicrobials in the future.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 51-60"},"PeriodicalIF":3.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: To evaluate the in vitro susceptibility of ESBL-producing Enterobacterales isolates to ceftolozane/tazobactam (C/T), a combination of tazobactam (a ß-lactamase inhibitor) and a new antipseudomonal cephalosporin.
Methods: From 2016 to 2019, susceptibilities of 10,545 Enterobacterales isolated from intra-abdominal, urinary tract, respiratory tract and bloodstream infections to C/T and 11 other antimicrobial agents were analyzed. Non-ESBL-producing isolates were included for comparative analysis to provide a comprehensive susceptibility profile.
Results: Among 10,545 isolated Enterobacterales, 54.6% were ESBL producers. The ESBL-positive rates for E. coli (984/10,545, 47.3%) and K. pneumoniae (3,606/10,545, 34.2%) were 59.8% and 51.1%, respectively. The susceptibility rate to C/T for all Enterobacterales was 79.5%. For E. coli and K. pneumoniae, the C/T susceptibilities were 89.3% and 68.0%, respectively. For non-ESBL-producing Enterobacterales, susceptibility to C/T was 99.5%. The susceptibility of non-carbapenem-resistant (CR) ESBL-producing Enterobacterales to C/T was 81.0%. The isolation rates of ESBL-positive and carbapenem-resistant Enterobacterales (CRE), CR-E. coli, and CR-K. pneumoniae were 14.3%, 5.6% and 26.8%, respectively. The susceptibility of ESBL-positive CREs to C/T was < 20% for most antimicrobials except amikacin (50.4%). The susceptibility of ESBL-positive CR-E. coli to C/T was 28.2. For ESBL-producing CR-K. pneumoniae, susceptibility to most antimicrobials was < 10%, except for amikacin (37.4%).
Conclusions: The present research underscores the viability of C/T as an alternative to carbapenems for the treatment of ESBL-producing, carbapenem susceptible Enterobacterales. However, the susceptibilities of ESBL-positive CRE to C/T and other studied antimicrobials were consistently below 20%, emphasizing for new innovative treatment strategies.
{"title":"In vitro activity of ceftolozane/tazobactam against ESBL-producing Enterobacterales in China: SMART 2016-2019 CE Level information received is 2T.","authors":"Wei Yu, Hui Zhang, Yingchun Xu, Ying Zhu, Peiyao Jia, Yue Kang, Qiwen Yang","doi":"10.1016/j.jgar.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.jgar.2025.02.001","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the in vitro susceptibility of ESBL-producing Enterobacterales isolates to ceftolozane/tazobactam (C/T), a combination of tazobactam (a ß-lactamase inhibitor) and a new antipseudomonal cephalosporin.</p><p><strong>Methods: </strong>From 2016 to 2019, susceptibilities of 10,545 Enterobacterales isolated from intra-abdominal, urinary tract, respiratory tract and bloodstream infections to C/T and 11 other antimicrobial agents were analyzed. Non-ESBL-producing isolates were included for comparative analysis to provide a comprehensive susceptibility profile.</p><p><strong>Results: </strong>Among 10,545 isolated Enterobacterales, 54.6% were ESBL producers. The ESBL-positive rates for E. coli (984/10,545, 47.3%) and K. pneumoniae (3,606/10,545, 34.2%) were 59.8% and 51.1%, respectively. The susceptibility rate to C/T for all Enterobacterales was 79.5%. For E. coli and K. pneumoniae, the C/T susceptibilities were 89.3% and 68.0%, respectively. For non-ESBL-producing Enterobacterales, susceptibility to C/T was 99.5%. The susceptibility of non-carbapenem-resistant (CR) ESBL-producing Enterobacterales to C/T was 81.0%. The isolation rates of ESBL-positive and carbapenem-resistant Enterobacterales (CRE), CR-E. coli, and CR-K. pneumoniae were 14.3%, 5.6% and 26.8%, respectively. The susceptibility of ESBL-positive CREs to C/T was < 20% for most antimicrobials except amikacin (50.4%). The susceptibility of ESBL-positive CR-E. coli to C/T was 28.2. For ESBL-producing CR-K. pneumoniae, susceptibility to most antimicrobials was < 10%, except for amikacin (37.4%).</p><p><strong>Conclusions: </strong>The present research underscores the viability of C/T as an alternative to carbapenems for the treatment of ESBL-producing, carbapenem susceptible Enterobacterales. However, the susceptibilities of ESBL-positive CRE to C/T and other studied antimicrobials were consistently below 20%, emphasizing for new innovative treatment strategies.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To describe the molecular characterisation of an Enterobacter cloacae strain resistant to cefiderocol and co-harbouring blaIMP-19 and mcr-4.3 resistance genes
Methods
The strain was isolated from the rectal swab of a 77-year-old woman during screening for the detection of patients colonised by carbapenemase-producing Enterobacterales (CPE) in Bologna (Italy). The strain was identified at species level by MALDI-TOF mass spectrometry and the presence of active-on-imipenem (IMP) carbapenemase was confirmed both by a phenotypic immunochromatographic method, and by a rapid commercial nucleic acid amplification test. The strain underwent antimicrobial susceptibility testing and its genome was fully characterised to assess (i) the multilocus sequence type, (ii) the presence of antimicrobial resistance (AMR) genes, and (iii) the presence of virulence genes coupled with mobile genetic elements.
Results
Multilocus sequence typing identified the strain as ST837. A plasmid of 60 691 bp, very similar to the MW574937 plasmid of Escherichia coli, was identified and carried the following AMR genes: aac(6′)-II, blaBEL-1, blaIMP-19, msr(E), mph(E), and sul1. This plasmid harboured several tra genes (traB, traC, traD, traG, traI, traJ, traKtraL, and traM) of the transfer operon of the E. coli conjugative F plasmid. Other AMR genes were located in the chromosome (blaCMH-3 and fosA) or in other plasmids (blaSHV-12 and mcr-4.3). The strain showed resistance to many β-lactams in vitro, including cefiderocol, whereas, despite the presence of the mcr-4.3 gene, it was susceptible to colistin.
Conclusions
Further studies are needed to better evaluate the origin of this strain and monitor the presence of Gram-negative bacilli with a similar molecular structure in our area.
{"title":"First report of an Enterobacter cloacae ST837 resistant to cefiderocol co-harbouring blaIMP-19 and mcr-4.3 resistance genes in Italy","authors":"Ilaria Menozzi , Erika Scaltriti , Benedetta Secci , Alessandra Dodi , Tiziana Lazzarotto , Stefano Pongolini , Claudio Foschi , Simone Ambretti","doi":"10.1016/j.jgar.2025.01.023","DOIUrl":"10.1016/j.jgar.2025.01.023","url":null,"abstract":"<div><h3>Objective</h3><div>To describe the molecular characterisation of an <em>Enterobacter cloacae</em> strain resistant to cefiderocol and co-harbouring <em>bla</em><sub>IMP-19</sub> and <em>mcr-4.3</em> resistance genes</div></div><div><h3>Methods</h3><div>The strain was isolated from the rectal swab of a 77-year-old woman during screening for the detection of patients colonised by carbapenemase-producing Enterobacterales (CPE) in Bologna (Italy). The strain was identified at species level by MALDI-TOF mass spectrometry and the presence of active-on-imipenem (IMP) carbapenemase was confirmed both by a phenotypic immunochromatographic method, and by a rapid commercial nucleic acid amplification test. The strain underwent antimicrobial susceptibility testing and its genome was fully characterised to assess (i) the multilocus sequence type, (ii) the presence of antimicrobial resistance (AMR) genes, and (iii) the presence of virulence genes coupled with mobile genetic elements.</div></div><div><h3>Results</h3><div>Multilocus sequence typing identified the strain as ST837. A plasmid of 60 691 bp, very similar to the MW574937 plasmid of <em>Escherichia coli</em>, was identified and carried the following AMR genes: <em>aac(6′)-II</em>, bla<sub>BEL-1</sub>, <em>bla</em><sub>IMP-19</sub>, <em>msr(E), mph(E)</em>, and <em>sul1.</em> This plasmid harboured several <em>tra</em> genes (<em>traB, traC, traD, traG, traI, traJ, traKtraL</em>, and <em>traM</em>) of the transfer operon of the <em>E. coli</em> conjugative F plasmid. Other AMR genes were located in the chromosome (<em>bla</em><sub>CMH-3</sub> and <em>fosA</em>) or in other plasmids (<em>bla</em><sub>SHV-12</sub> and <em>mcr-4.3</em>). The strain showed resistance to many β-lactams in vitro, including cefiderocol, whereas, despite the presence of the <em>mcr-4.3</em> gene, it was susceptible to colistin.</div></div><div><h3>Conclusions</h3><div>Further studies are needed to better evaluate the origin of this strain and monitor the presence of Gram-negative bacilli with a similar molecular structure in our area.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 37-41"},"PeriodicalIF":3.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-11DOI: 10.1016/j.jgar.2025.01.022
Aimee Songo, Hervé Jacquier, Maxime Danjean, Fabrice Compain, Delphine Dorchène, Zainab Edoo, Paul-Louis Woerther, Michel Arthur, David Lebeaux
Objective: Molecular determinants of β-lactam resistance are poorly explored for most Nocardia species, such as Nocardia brasiliensis. In this study, we characterised resistance mediated by two β-lactamases in the reference strain N. brasiliensis HUJEG-1 and extended our analysis to nine N. brasiliensis clinical strains.
Methods: The susceptibility of N. brasiliensis HUJEG-1 was determined by measuring the MIC via microdilution for five β-lactam antibiotics that were or were not associated with β-lactamase inhibitors (clavulanate and avibactam, 4 µg/mL). Two putative class A β-lactamase-encoding genes (blaBRA-1 and blaBRS-1) were identified in the HUJEG-1 genome. The kinetic parameters of purified BRA-1 and BRS-1 were determined by spectrophotometry. Measurement of β-lactam resistance was then extended to nine clinical strains. These phenotypic data were compared with the genomic diversity of whole genomes (next-generation sequencing).
Results: N. brasiliensis HUJEG-1 was resistant to amoxicillin, cefuroxime, and cefotaxime, but susceptible to their combination with clavulanate or avibactam. This strain was resistant to imipenem (with or without inhibitors) and susceptible to meropenem. BRA-1 showed high catalytic efficiencies against penams (penicillin, ampicillin) and cephems (cephaloridine, cephalothin, and cefamandole), but not against penems (imipenem, meropenem), suggesting that imipenem resistance was mediated by another mechanism. The hydrolytic activity of BRS-1 was 100-1000-fold lower than that of BRA-1 for all β-lactams tested, suggesting that BRS-1 has a minor contribution to β-lactam resistance. Analysis of the nine clinical strains showed variations in susceptibility to cefotaxime, as well as diversity in genetic backgrounds and BRA-1 sequences.
Conclusions: N. brasiliensis HUJEG-1 resistance to penams and cephems is mainly due to the class A β-lactamase BRA-1.
{"title":"Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibiotics.","authors":"Aimee Songo, Hervé Jacquier, Maxime Danjean, Fabrice Compain, Delphine Dorchène, Zainab Edoo, Paul-Louis Woerther, Michel Arthur, David Lebeaux","doi":"10.1016/j.jgar.2025.01.022","DOIUrl":"10.1016/j.jgar.2025.01.022","url":null,"abstract":"<p><strong>Objective: </strong>Molecular determinants of β-lactam resistance are poorly explored for most Nocardia species, such as Nocardia brasiliensis. In this study, we characterised resistance mediated by two β-lactamases in the reference strain N. brasiliensis HUJEG-1 and extended our analysis to nine N. brasiliensis clinical strains.</p><p><strong>Methods: </strong>The susceptibility of N. brasiliensis HUJEG-1 was determined by measuring the MIC via microdilution for five β-lactam antibiotics that were or were not associated with β-lactamase inhibitors (clavulanate and avibactam, 4 µg/mL). Two putative class A β-lactamase-encoding genes (bla<sub>BRA-1</sub> and bla<sub>BRS-1</sub>) were identified in the HUJEG-1 genome. The kinetic parameters of purified BRA-1 and BRS-1 were determined by spectrophotometry. Measurement of β-lactam resistance was then extended to nine clinical strains. These phenotypic data were compared with the genomic diversity of whole genomes (next-generation sequencing).</p><p><strong>Results: </strong>N. brasiliensis HUJEG-1 was resistant to amoxicillin, cefuroxime, and cefotaxime, but susceptible to their combination with clavulanate or avibactam. This strain was resistant to imipenem (with or without inhibitors) and susceptible to meropenem. BRA-1 showed high catalytic efficiencies against penams (penicillin, ampicillin) and cephems (cephaloridine, cephalothin, and cefamandole), but not against penems (imipenem, meropenem), suggesting that imipenem resistance was mediated by another mechanism. The hydrolytic activity of BRS-1 was 100-1000-fold lower than that of BRA-1 for all β-lactams tested, suggesting that BRS-1 has a minor contribution to β-lactam resistance. Analysis of the nine clinical strains showed variations in susceptibility to cefotaxime, as well as diversity in genetic backgrounds and BRA-1 sequences.</p><p><strong>Conclusions: </strong>N. brasiliensis HUJEG-1 resistance to penams and cephems is mainly due to the class A β-lactamase BRA-1.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":"135-141"},"PeriodicalIF":3.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-03DOI: 10.1016/j.jgar.2025.01.012
Guangfen Zhang , Chunli Li , Xiaofan Li , Yuanyuan Li , Yunbing Li , Xiangkun Zeng , Chen Xu , Shuyan Wu , Ning Dong
Refractory infections caused by multidrug-resistant bacteria pose a significant threat to public health. Here we report that ibuprofen inhibits conjugation of the RP4 plasmid and plasmids from clinical strains carrying different resistance genes including mcr-1, blaNDM, blaKPC, tet(X4), and tmexCD1-toprJ1. Mechanistic studies suggest that ibuprofen reduces ATP production and inhibits conjugation-related genes. The inhibitory effect of ibuprofen on conjugation has significant clinical implications for preventing the spread of multidrug resistance, opening new therapeutic avenues to combat multidrug-resistant bacteria.
{"title":"Ibuprofen prevents the conjugative transfer of plasmid-mediated antimicrobial resistance genes","authors":"Guangfen Zhang , Chunli Li , Xiaofan Li , Yuanyuan Li , Yunbing Li , Xiangkun Zeng , Chen Xu , Shuyan Wu , Ning Dong","doi":"10.1016/j.jgar.2025.01.012","DOIUrl":"10.1016/j.jgar.2025.01.012","url":null,"abstract":"<div><div>Refractory infections caused by multidrug-resistant bacteria pose a significant threat to public health. Here we report that ibuprofen inhibits conjugation of the RP4 plasmid and plasmids from clinical strains carrying different resistance genes including <em>mcr-1, bla</em><sub>NDM</sub>, <em>bla</em><sub>KPC</sub>, <em>tet</em>(X4), and <em>tmexCD1</em>-<em>toprJ1</em>. Mechanistic studies suggest that ibuprofen reduces ATP production and inhibits conjugation-related genes. The inhibitory effect of ibuprofen on conjugation has significant clinical implications for preventing the spread of multidrug resistance, opening new therapeutic avenues to combat multidrug-resistant bacteria.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 10-14"},"PeriodicalIF":3.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jgar.2025.01.011
Hazim O. Khalifa , Shizuo Kayama , Mohammed Elbediwi , Liansheng Yu , Wataru Hayashi , Yo Sugawara , Mohamed-Yousif Ibrahim Mohamed , Hazem Ramadan , Ihab Habib , Tetsuya Matsumoto , Motoyuki Sugai
Objective
To investigate the genetic basis of carbapenem resistance in clinical Serratia marcescens isolates collected from patients in Japan between 1994 and 2016. A total of 5135 clinical isolates of S. marcescens were recovered from different medical centres across Japan, identified in central laboratories, and tested for antimicrobial agents using the broth microdilution method.
Methods
All the isolates that showed intermediate or resistant phenotypes for at least one carbapenem antibiotic were confirmed by antimicrobial susceptibility testing and for carbapenemase production by the modified carbapenem inactivation method. Furthermore, full genetic characterization was performed by whole genome sequencing for all the isolates.
Results
Based on our findings, 27 isolates (0.53%) exhibited resistance to ertapenem and/or meropenem. Among these, 10 isolates were phenotypically confirmed as carbapenemase producers using the modified carbapenem inactivation method test. The isolates were resistant to a wide range of antibiotics including β-lactams (48.1%–100%), two fluoroquinolones (77.8%–88.9%), tigecycline and minocycline (70.4% each), and sulfamethoxazole-trimethoprim (55.6%). Whole-genome sequencing was conducted on all carbapenem-resistant strains, uncovering blaIMP in eight isolates, comprising seven with blaIMP-1 and one with blaIMP-11, alongside multiple antimicrobial resistance determinants. Importantly, the phylogenomic comparison with international S. marcescens isolates revealed genetic relatedness and potential cross-border transmission events.
Conclusions
Our findings underscore the importance of enhanced surveillance and infection control measures to mitigate the dissemination of multidrug-resistant pathogens, emphasizing the need for international collaboration and coordinated efforts to address antimicrobial resistance on a global scale.
{"title":"Genetic basis of carbapenem-resistant clinical Serratia marcescens in Japan","authors":"Hazim O. Khalifa , Shizuo Kayama , Mohammed Elbediwi , Liansheng Yu , Wataru Hayashi , Yo Sugawara , Mohamed-Yousif Ibrahim Mohamed , Hazem Ramadan , Ihab Habib , Tetsuya Matsumoto , Motoyuki Sugai","doi":"10.1016/j.jgar.2025.01.011","DOIUrl":"10.1016/j.jgar.2025.01.011","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the genetic basis of carbapenem resistance in clinical <em>Serratia marcescens</em> isolates collected from patients in Japan between 1994 and 2016. A total of 5135 clinical isolates of <em>S. marcescens</em> were recovered from different medical centres across Japan, identified in central laboratories, and tested for antimicrobial agents using the broth microdilution method.</div></div><div><h3>Methods</h3><div>All the isolates that showed intermediate or resistant phenotypes for at least one carbapenem antibiotic were confirmed by antimicrobial susceptibility testing and for carbapenemase production by the modified carbapenem inactivation method. Furthermore, full genetic characterization was performed by whole genome sequencing for all the isolates.</div></div><div><h3>Results</h3><div>Based on our findings, 27 isolates (0.53%) exhibited resistance to ertapenem and/or meropenem. Among these, 10 isolates were phenotypically confirmed as carbapenemase producers using the modified carbapenem inactivation method test. The isolates were resistant to a wide range of antibiotics including β-lactams (48.1%–100%), two fluoroquinolones (77.8%–88.9%), tigecycline and minocycline (70.4% each), and sulfamethoxazole-trimethoprim (55.6%). Whole-genome sequencing was conducted on all carbapenem-resistant strains, uncovering <em>bla</em><sub>IMP</sub> in eight isolates, comprising seven with <em>bla</em><sub>IMP-1</sub> and one with <em>bla</em><sub>IMP-11</sub>, alongside multiple antimicrobial resistance determinants. Importantly, the phylogenomic comparison with international <em>S. marcescens</em> isolates revealed genetic relatedness and potential cross-border transmission events.</div></div><div><h3>Conclusions</h3><div>Our findings underscore the importance of enhanced surveillance and infection control measures to mitigate the dissemination of multidrug-resistant pathogens, emphasizing the need for international collaboration and coordinated efforts to address antimicrobial resistance on a global scale.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 28-36"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.jgar.2025.01.020
Carlton Cannon , Seon Woo Kim , Jung-lim Lee , Jo Ann S. Van Kessel , Bradd J. Haley
Objective
Raoultella planticola is an emerging opportunistic pathogen closely related to members of the Klebsiella genus. Genomic characterization of R. planticola isolates recovered from food animals is lacking. Here we describe the antimicrobial resistance genes, virulence factors, plasmid replicons, and phylogeny of three antimicrobial-resistant R. planticola isolates recovered from the feces of three dairy calves within 48 hours of birth.
Methods
The genomes of the three R. planticola isolates were sequenced on a NextSeq 2000 platform using paired-end sequencing. The raw reads were trimmed using Trimmomatic and assembled using SPAdes v 3.15.4. Antimicrobial resistance genes, virulence factors and plasmid replicons were identified using ABRicate. Single nucleotide polymorphisms were identified among the genomes using the Harvest package and phylogenies were inferred using RAxML.
Results
In total, nine different ARGs known to confer resistance to at least five different classes of antibiotics were detected among the three R. planticola genomes. These include blaPLA, a β-lactamase found only in R. planticola, fosfomycin resistance gene fosA, and a sequence aligned with oxqAB, an efflux pump conferring resistance to antibiotics including fluoroquinolones. Each genome encoded between four and seven ARGs, with three considered genotypically to be multidrug-resistant (MDR). Two of the three genomes harbored plasmids, and all three encoded 41–42 virulence factors, including iron scavenging genes sitABCD.
Conclusions
Results of this study demonstrate the presence of diverse antimicrobial-resistant R. planticola, isolated from the feces of healthy dairy calves, that had some virulence factors that may cause human disease.
{"title":"Antimicrobial-resistant raoultella planticola isolated from preweaned dairy calf feces","authors":"Carlton Cannon , Seon Woo Kim , Jung-lim Lee , Jo Ann S. Van Kessel , Bradd J. Haley","doi":"10.1016/j.jgar.2025.01.020","DOIUrl":"10.1016/j.jgar.2025.01.020","url":null,"abstract":"<div><h3>Objective</h3><div><em>Raoultella planticola</em> is an emerging opportunistic pathogen closely related to members of the <em>Klebsiella</em> genus. Genomic characterization of <em>R. planticola</em> isolates recovered from food animals is lacking. Here we describe the antimicrobial resistance genes, virulence factors, plasmid replicons, and phylogeny of three antimicrobial-resistant <em>R. planticola</em> isolates recovered from the feces of three dairy calves within 48 hours of birth.</div></div><div><h3>Methods</h3><div>The genomes of the three <em>R. planticola</em> isolates were sequenced on a NextSeq 2000 platform using paired-end sequencing. The raw reads were trimmed using Trimmomatic and assembled using SPAdes v 3.15.4. Antimicrobial resistance genes, virulence factors and plasmid replicons were identified using ABRicate. Single nucleotide polymorphisms were identified among the genomes using the Harvest package and phylogenies were inferred using RAxML.</div></div><div><h3>Results</h3><div>In total, nine different ARGs known to confer resistance to at least five different classes of antibiotics were detected among the three <em>R. planticola</em> genomes. These include <em>bla</em><sub>PLA</sub>, a β-lactamase found only in <em>R. planticola,</em> fosfomycin resistance gene <em>fosA,</em> and a sequence aligned with <em>oxqAB</em>, an efflux pump conferring resistance to antibiotics including fluoroquinolones. Each genome encoded between four and seven ARGs, with three considered genotypically to be multidrug-resistant (MDR). Two of the three genomes harbored plasmids, and all three encoded 41–42 virulence factors, including iron scavenging genes <em>sitABCD</em>.</div></div><div><h3>Conclusions</h3><div>Results of this study demonstrate the presence of diverse antimicrobial-resistant <em>R. planticola</em>, isolated from the feces of healthy dairy calves, that had some virulence factors that may cause human disease.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 98-99"},"PeriodicalIF":3.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-30DOI: 10.1016/j.jgar.2025.01.013
Ikuri Alvarez-Maya , Manuel Garcia-Ulloa , Armando Martinez-Guarneros , Carlos A. Vazquez-Chacon , Jaime Martinez-Urtaza
Background
Tuberculosis disease is a major global health concern. In Mexico, information regarding the genomic variants of Mycobacterium tuberculosis (MTB) prevailing in the country and the existence of specific biogeographical patterns remains extremely scarce.
Objective
This study aimed to identify the genotypic patterns of MTB isolates in Mexico and determine the genes and specific single nucleotide polymorphisms involved in the evolution of these populations.
Methods
Phylogenomic and pan-genomic analyses were performed using publicly available Mexican MTB genomes along with 33 newly sequenced genomes from Jalisco, considering a global context.
Results
The L4 sublineages of MTB, such as L4.1.1 (X), L4.1.2 (H), and L4.3 (LAM), were the most prevalent in Mexico. We found exclusive mutations and gene clusters in a virulent sublineage L4.1.1.3 (X3), which is endemic to Mexico. These genes encoded three PE/PPE family proteins: a multidrug transporter, thioredoxin domain-containing protein, quinone-dependent l-lactate dehydrogenase, DUF1725 domain-containing protein, amidase, poly (A) polymerase, and six hypothetical/uncharacterised proteins. Additionally, the genes encode an ESX-1 secretion-associated protein and a deazaflavin-dependent nitroreductase (ddn).
Conclusion
X3 was distinguished from the rest of the sublineages by containing genes related to pathogenicity and virulence, as well as a gene linked to delamanid, an antibiotic for active multidrug-resistant tuberculosis. These findings provide valuable insight into the circulation and spread of MTB in Mexico.
{"title":"Nationwide phylogenomic surveillance of Mycobacterium tuberculosis in Mexico reveals pathogenic and drug resistant signatures of the prevailing L4 sublineage","authors":"Ikuri Alvarez-Maya , Manuel Garcia-Ulloa , Armando Martinez-Guarneros , Carlos A. Vazquez-Chacon , Jaime Martinez-Urtaza","doi":"10.1016/j.jgar.2025.01.013","DOIUrl":"10.1016/j.jgar.2025.01.013","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculosis disease is a major global health concern. In Mexico, information regarding the genomic variants of <em>Mycobacterium tuberculosis</em> (MTB) prevailing in the country and the existence of specific biogeographical patterns remains extremely scarce.</div></div><div><h3>Objective</h3><div>This study aimed to identify the genotypic patterns of MTB isolates in Mexico and determine the genes and specific single nucleotide polymorphisms involved in the evolution of these populations.</div></div><div><h3>Methods</h3><div>Phylogenomic and pan-genomic analyses were performed using publicly available Mexican MTB genomes along with 33 newly sequenced genomes from Jalisco, considering a global context.</div></div><div><h3>Results</h3><div>The L4 sublineages of MTB, such as L4.1.1 (X), L4.1.2 (H), and L4.3 (LAM), were the most prevalent in Mexico. We found exclusive mutations and gene clusters in a virulent sublineage L4.1.1.3 (X3), which is endemic to Mexico. These genes encoded three PE/PPE family proteins: a multidrug transporter, thioredoxin domain-containing protein, quinone-dependent <span>l</span>-lactate dehydrogenase, DUF1725 domain-containing protein, amidase, poly (A) polymerase, and six hypothetical/uncharacterised proteins. Additionally, the genes encode an ESX-1 secretion-associated protein and a deazaflavin-dependent nitroreductase (<em>ddn</em>).</div></div><div><h3>Conclusion</h3><div>X3 was distinguished from the rest of the sublineages by containing genes related to pathogenicity and virulence, as well as a gene linked to delamanid, an antibiotic for active multidrug-resistant tuberculosis. These findings provide valuable insight into the circulation and spread of MTB in Mexico.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"41 ","pages":"Pages 224-232"},"PeriodicalIF":3.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aims to investigate the effectiveness of UIO-66-NH2, a metal-organic framework, as a carrier for imipenem/cilastatin (Imp/Cil) in overcoming resistance in clinical isolates of imipenem-resistant Pseudomonas aeruginosa.
Methods
The UIO-66-NH2-Imp/Cil formulations were synthesized and characterized using dynamic light scattering, scanning electron microscopy, and transmission electron microscopy. Drug entrapment efficiency of UIO-66-NH2-Imp/Cil, and Imp/Cil release rates were determined. The stability of formulations was assessed at room temperature and refrigeration for two months. The antibacterial, anti-biofilm, and anti-virulence activities of formulations were investigated against imipenem-resistant P. aeruginosa isolates.
Results
The UIO-66-NH2-Imp/Cil formulation showed an average particle size of 212.3 ± 7.3 nm, a polydispersity index of 0.142 ± 0.010, and an entrapment efficiency (EE%) of 74.19% ± 1.12%. Drug release from the formulation followed a Korsmeyer-Peppas kinetic model, with 52% of the drug released over 72 h. Antibacterial testing indicated a significant decrease in minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the UIO-66-NH2-Imp/Cil formulation compared to free Imp/Cil, demonstrating enhanced antibacterial activity. Furthermore, the anti-biofilm and anti-virulence activity of UIO-66-NH2-Imp/Cil was confirmed by the reduction of bacterial haemolysis activity, minimal pyocyanin, EPS (extracellular polymeric substance) production, and lower metabolic activity of pathogens. Also, UIO-66-NH2-Imp/Cil causes significant reduction in the expression of lasA, lasB and, rhlA genes, which resulted in the inhibition of quorum-sensing system activity.
Conclusions
These findings indicate that UIO-66-NH2-Imp/Cil nanocarriers offer a promising new approach against multidrug-resistant Gram-negative pathogens, providing insights into potential mechanisms of antimicrobial action.
{"title":"Imipenem/cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates","authors":"Shakila Baei Lashaki , Pooria Moulavi , Fatemeh Ashrafi , Aram Sharifi , Sepideh Asadi","doi":"10.1016/j.jgar.2025.01.010","DOIUrl":"10.1016/j.jgar.2025.01.010","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to investigate the effectiveness of UIO-66-NH<sub>2</sub>, a metal-organic framework, as a carrier for imipenem/cilastatin (Imp/Cil) in overcoming resistance in clinical isolates of imipenem-resistant <em>Pseudomonas aeruginosa</em>.</div></div><div><h3>Methods</h3><div>The UIO-66-NH<sub>2</sub>-Imp/Cil formulations were synthesized and characterized using dynamic light scattering, scanning electron microscopy, and transmission electron microscopy. Drug entrapment efficiency of UIO-66-NH<sub>2</sub>-Imp/Cil, and Imp/Cil release rates were determined. The stability of formulations was assessed at room temperature and refrigeration for two months. The antibacterial, anti-biofilm, and anti-virulence activities of formulations were investigated against imipenem-resistant <em>P. aeruginosa</em> isolates.</div></div><div><h3>Results</h3><div>The UIO-66-NH<sub>2</sub>-Imp/Cil formulation showed an average particle size of 212.3 ± 7.3 nm, a polydispersity index of 0.142 ± 0.010, and an entrapment efficiency (EE%) of 74.19% ± 1.12%. Drug release from the formulation followed a Korsmeyer-Peppas kinetic model, with 52% of the drug released over 72 h. Antibacterial testing indicated a significant decrease in minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the UIO-66-NH<sub>2</sub>-Imp/Cil formulation compared to free Imp/Cil, demonstrating enhanced antibacterial activity. Furthermore, the anti-biofilm and anti-virulence activity of UIO-66-NH<sub>2</sub>-Imp/Cil was confirmed by the reduction of bacterial haemolysis activity, minimal pyocyanin, EPS (extracellular polymeric substance) production, and lower metabolic activity of pathogens. Also, UIO-66-NH<sub>2</sub>-Imp/Cil causes significant reduction in the expression of <em>lasA, lasB</em> and, <em>rhlA</em> genes, which resulted in the inhibition of quorum-sensing system activity.</div></div><div><h3>Conclusions</h3><div>These findings indicate that UIO-66-NH<sub>2</sub>-Imp/Cil nanocarriers offer a promising new approach against multidrug-resistant Gram-negative pathogens, providing insights into potential mechanisms of antimicrobial action.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 15-27"},"PeriodicalIF":3.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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