Shane Whelan , Francesca Bottacini , Colin Buttimer , Karen Finn , Brigid Lucey
{"title":"爱尔兰尿路致病性大肠杆菌的全基因组测序揭示了多种耐药机制,并与表型(EUCAST)药敏试验密切相关","authors":"Shane Whelan , Francesca Bottacini , Colin Buttimer , Karen Finn , Brigid Lucey","doi":"10.1016/j.meegid.2024.105600","DOIUrl":null,"url":null,"abstract":"<div><p>Urinary tract infections (UTI) caused by uropathogenic <em>Escherichia coli</em> (UPEC) pose a global health concern. Resistance mechanisms, including genetic mutations in antimicrobial target genes, efflux pumps, and drug deactivating enzymes, hinder clinical treatment. These resistance factors often spread through mobile genetic elements. Molecular techniques like whole genome sequencing (WGS), multilocus sequence typing (MLST), and phylotyping help decode bacterial genomes and categorise resistance genes.</p><p>In this study, we analysed 57 UPEC isolates from different UTI patients following EUCAST guidelines. A selection of 17 representative strains underwent WGS, phylotyping, MLST, and comparative analysis to connect laboratory susceptibility data with predictive genomics based on key resistance genes and chromosomal mutations in antimicrobial targets.</p><p>Trimethoprim resistance consistently correlated with <em>dfr</em> genes, with six different alleles detected among the isolates. These <em>dfr</em> genes often coexisted with class 1 integrons, with the most common gene cassette combining <em>dfr</em> and <em>aadA</em>. Furthermore, 52.9% of isolates harboured the <em>bla</em><sup><em>Tem-1</em></sup> gene, rendering resistance to ampicillin and amoxicillin. Ciprofloxacin-resistant strains exhibited mutations in GyrA, GyrB and ParC, plasmid-mediated quinolone resistance genes (<em>qnrb10</em>), and <em>aac(6′)-Ib-cr5.</em> Nitrofurantoin resistance in one isolate stemmed from a four amino acid deletion in NfsB.</p><p>These findings illustrate the varied strategies employed by UPEC to resist antibiotics and the correlation between clinical susceptibility testing and molecular determinants. As molecular testing gains prominence in clinical applications, understanding key resistance determinants becomes crucial for accurate susceptibility testing and guiding effective antimicrobial therapy.</p></div>","PeriodicalId":54986,"journal":{"name":"Infection Genetics and Evolution","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567134824000510/pdfft?md5=d0e848887134c663496cf3edc74b9bf5&pid=1-s2.0-S1567134824000510-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Whole genome sequencing of uropathogenic E. coli from Ireland reveals diverse resistance mechanisms and strong correlation with phenotypic (EUCAST) susceptibility testing\",\"authors\":\"Shane Whelan , Francesca Bottacini , Colin Buttimer , Karen Finn , Brigid Lucey\",\"doi\":\"10.1016/j.meegid.2024.105600\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Urinary tract infections (UTI) caused by uropathogenic <em>Escherichia coli</em> (UPEC) pose a global health concern. Resistance mechanisms, including genetic mutations in antimicrobial target genes, efflux pumps, and drug deactivating enzymes, hinder clinical treatment. These resistance factors often spread through mobile genetic elements. Molecular techniques like whole genome sequencing (WGS), multilocus sequence typing (MLST), and phylotyping help decode bacterial genomes and categorise resistance genes.</p><p>In this study, we analysed 57 UPEC isolates from different UTI patients following EUCAST guidelines. A selection of 17 representative strains underwent WGS, phylotyping, MLST, and comparative analysis to connect laboratory susceptibility data with predictive genomics based on key resistance genes and chromosomal mutations in antimicrobial targets.</p><p>Trimethoprim resistance consistently correlated with <em>dfr</em> genes, with six different alleles detected among the isolates. These <em>dfr</em> genes often coexisted with class 1 integrons, with the most common gene cassette combining <em>dfr</em> and <em>aadA</em>. Furthermore, 52.9% of isolates harboured the <em>bla</em><sup><em>Tem-1</em></sup> gene, rendering resistance to ampicillin and amoxicillin. Ciprofloxacin-resistant strains exhibited mutations in GyrA, GyrB and ParC, plasmid-mediated quinolone resistance genes (<em>qnrb10</em>), and <em>aac(6′)-Ib-cr5.</em> Nitrofurantoin resistance in one isolate stemmed from a four amino acid deletion in NfsB.</p><p>These findings illustrate the varied strategies employed by UPEC to resist antibiotics and the correlation between clinical susceptibility testing and molecular determinants. 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Whole genome sequencing of uropathogenic E. coli from Ireland reveals diverse resistance mechanisms and strong correlation with phenotypic (EUCAST) susceptibility testing
Urinary tract infections (UTI) caused by uropathogenic Escherichia coli (UPEC) pose a global health concern. Resistance mechanisms, including genetic mutations in antimicrobial target genes, efflux pumps, and drug deactivating enzymes, hinder clinical treatment. These resistance factors often spread through mobile genetic elements. Molecular techniques like whole genome sequencing (WGS), multilocus sequence typing (MLST), and phylotyping help decode bacterial genomes and categorise resistance genes.
In this study, we analysed 57 UPEC isolates from different UTI patients following EUCAST guidelines. A selection of 17 representative strains underwent WGS, phylotyping, MLST, and comparative analysis to connect laboratory susceptibility data with predictive genomics based on key resistance genes and chromosomal mutations in antimicrobial targets.
Trimethoprim resistance consistently correlated with dfr genes, with six different alleles detected among the isolates. These dfr genes often coexisted with class 1 integrons, with the most common gene cassette combining dfr and aadA. Furthermore, 52.9% of isolates harboured the blaTem-1 gene, rendering resistance to ampicillin and amoxicillin. Ciprofloxacin-resistant strains exhibited mutations in GyrA, GyrB and ParC, plasmid-mediated quinolone resistance genes (qnrb10), and aac(6′)-Ib-cr5. Nitrofurantoin resistance in one isolate stemmed from a four amino acid deletion in NfsB.
These findings illustrate the varied strategies employed by UPEC to resist antibiotics and the correlation between clinical susceptibility testing and molecular determinants. As molecular testing gains prominence in clinical applications, understanding key resistance determinants becomes crucial for accurate susceptibility testing and guiding effective antimicrobial therapy.
期刊介绍:
(aka Journal of Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases -- MEEGID)
Infectious diseases constitute one of the main challenges to medical science in the coming century. The impressive development of molecular megatechnologies and of bioinformatics have greatly increased our knowledge of the evolution, transmission and pathogenicity of infectious diseases. Research has shown that host susceptibility to many infectious diseases has a genetic basis. Furthermore, much is now known on the molecular epidemiology, evolution and virulence of pathogenic agents, as well as their resistance to drugs, vaccines, and antibiotics. Equally, research on the genetics of disease vectors has greatly improved our understanding of their systematics, has increased our capacity to identify target populations for control or intervention, and has provided detailed information on the mechanisms of insecticide resistance.
However, the genetics and evolutionary biology of hosts, pathogens and vectors have tended to develop as three separate fields of research. This artificial compartmentalisation is of concern due to our growing appreciation of the strong co-evolutionary interactions among hosts, pathogens and vectors.
Infection, Genetics and Evolution and its companion congress [MEEGID](http://www.meegidconference.com/) (for Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases) are the main forum acting for the cross-fertilization between evolutionary science and biomedical research on infectious diseases.
Infection, Genetics and Evolution is the only journal that welcomes articles dealing with the genetics and evolutionary biology of hosts, pathogens and vectors, and coevolution processes among them in relation to infection and disease manifestation. All infectious models enter the scope of the journal, including pathogens of humans, animals and plants, either parasites, fungi, bacteria, viruses or prions. The journal welcomes articles dealing with genetics, population genetics, genomics, postgenomics, gene expression, evolutionary biology, population dynamics, mathematical modeling and bioinformatics. We also provide many author benefits, such as free PDFs, a liberal copyright policy, special discounts on Elsevier publications and much more. Please click here for more information on our author services .