Microbial Genomics最新文献

{"title":"Birmingham-group IncP-1<i>α</i> plasmids revisited: RP4, RP1 and RK2 are identical and their remnants can be detected in environmental isolates.","authors":"Vuong Van Hung Le, Zhuang Gong, Lorrie Maccario, Emma Bousquet, Boris Parra, Arnaud Dechesne, Søren J Sørensen, Joseph Nesme","doi":"10.1099/mgen.0.001381","DOIUrl":"10.1099/mgen.0.001381","url":null,"abstract":"<p><p>RP4, RP1, RK2 and R68 were isolated from the multidrug-resistant bacterial wound isolates in 1969 in the Birmingham Accident Hospital, Birmingham, England, and collectively called Birmingham-group IncP-1<i>α</i> plasmids. These plasmids have been widely used as models to study different aspects of plasmid biology, develop genetic delivery systems and design plasmid vectors. Early studies showed that these plasmids conferred the same antibiotic resistance profile, had a similar size and were undistinguishable from each other using DNA heteroduplex electron microscopy and restriction endonuclease analyses. These observations have led to the widely held assumption that they are identical, although there has been no conclusive supporting evidence. In this work, we sequenced the plasmids RP1 and RP4 from our laboratory strain collection and compared these new sequences with the plasmids RP4 and RK2 assembled from a publicly available sequencing database, showing that the RP1, RP4 and RK2 plasmids are 60 095 bp in length and identical at the nucleotide resolution. Noteworthily, the plasmid sequence is highly conserved despite having been distributed to different labs over 50 years and propagated in different bacterial hosts, strengthening the previous observation that the bacterial host adapts to the RP4/RP1/RK2 plasmid rather than the opposite. In the updated RP4/RP1/RK2 sequence, we found a fusion gene, called <i>pecM-orf2</i>, that was formed putatively by a genetic deletion event. By searching for <i>pecM-orf2</i> in the National Center for Biotechnology Information database, we detected remnants of the RP4/RP1/RK2 plasmid that carry features of laboratory-engineered vectors in bacterial environmental isolates, either in their chromosome or as a plasmid. This suggests a leak of these plasmids from the laboratory into the environment, which may subsequently impact bacterial evolution and raises concerns about the biocontainment of engineered plasmids when being handled in laboratory settings.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"11 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular epidemiology of a multidrug-resistant <i>Shigella sonnei</i> outbreak in Tunisia (2022-2023) using whole-genome sequencing.","authors":"Fahmi Smaoui, Boutheina Ksibi, Senda Mezghani, Eya Guermazi, Fatma Charfi, Sonia Ktari, Nourelhouda Ben Ayed, Thouraya Kammoun, Héla Karray, Adnene Hammami","doi":"10.1099/mgen.0.001362","DOIUrl":"10.1099/mgen.0.001362","url":null,"abstract":"<p><p><b>Purpose.</b> The prevalence of multidrug-resistant (MDR) <i>Shigella sonnei</i> is increasing globally, raising concerns for public health. In 2022, an outbreak of MDR <i>S. sonnei</i> was observed in Tunisia. We aimed to evaluate the genetic profile of <i>S. sonnei</i> isolates during the outbreak, including their clonal relationship, antimicrobial determinants and connection to international strains.<b>Methods.</b> In this study, we sequenced the whole genome of 24 S. <i>sonnei</i> strains collected from South Tunisia between July 2022 and November 2023. Bioinformatic analysis was conducted to confirm species identification, assign sequence types, determine core genome sequence types, analyse phylogenetic relationships and identify antimicrobial resistance determinants. Phylodynamic and phylogeographic analyses were performed to trace the spatiotemporal spread of the outbreak genotype.<b>Results.</b> Our investigation revealed that 23 out of 24 isolates were grouped into the HC10-20662 genotype within the 3.6.3 subclade. All isolates carried the <i>blaCTX-M-15</i> gene associated with extended-spectrum beta-lactamase production, as well as the <i>dfrA1</i> and <i>qnrS1</i> genes, along with the D87G mutation in <i>gyrA</i>. Additionally, the s<i>ul2, tet(A</i>) and <i>mph(A</i>) resistance genes were present in most isolates (96%, 96 and 83, respectively). Phylogeographic analysis suggested that the outbreak genotype likely spread in Europe before being introduced into Tunisia.<b>Conclusion.</b> To the best of our knowledge, this is the first MDR <i>S. sonnei</i> outbreak in the country. The HC10-20662 genotype appears to be responsible for a multi-country outbreak, affecting both Tunisia and Europe. Continued genomic surveillance efforts, both nationally and internationally, are essential for monitoring the dynamic evolution and global spread of MDR <i>S. sonnei</i>.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"11 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effect of monoterpenes and flavonoids on the transcription of aromatic ring-hydroxylating dioxygenase genes in <i>Rhodococcus opacus</i> C1 and <i>Rhodococcus</i> sp. WAY2.","authors":"Andrea Zubrova, Manuela Tadrosova, Jaroslav Semerad, Tomas Cajthaml, Petr Pajer, Michal Strejcek, Jachym Suman, Ondrej Uhlik","doi":"10.1099/mgen.0.001359","DOIUrl":"10.1099/mgen.0.001359","url":null,"abstract":"<p><p>Aromatic ring-hydroxylating dioxygenases (ARHDs) play a crucial role in the aerobic biodegradation of both natural and anthropogenic aromatic compounds. Although their ability to process contaminants is not entirely understood, it is thought to have evolved from the transformation of structurally similar secondary plant metabolites (SPMs). Hence, to investigate this connection, we tested a variety of SPMs from the monoterpene and flavonoid classes as carbon sources and transcriptional effectors of several phylogenetically distant ARHD genes involved in the degradation of aromatic pollutants. Specifically, we focused on <i>bphA1</i>, <i>nahA1</i> and <i>phtA1</i> in <i>Rhodococcus opacus</i> C1, whose genomic analysis is also presented hereinafter, and <i>bphA1a</i>, <i>nahA1-bphA1b</i> and <i>etbA1ab</i> in <i>Rhodococcu</i>s sp. WAY2. Whilst induction was only observed with (<i>R</i>)-carvone for <i>bphA1a</i> and <i>nahA1-bphA1b</i> of strain WAY2, and with <i>p</i>-cymene for <i>nahA1</i> and <i>nahA1-bphA1b</i> of strains C1 and WAY2, respectively, an extensive inhibition by flavonoids was observed for most of the genes in both strains. To the best of our knowledge, our study is the first to report the effect of flavonoids and monoterpenes on the transcription of <i>nahA1</i>, <i>etbA1</i> and <i>phtA1</i> genes. In addition, we show that, in contrast to pseudomonads, many flavonoids inhibit the transcription of the ARHD genes in rhodococci. Thus, our work provides a new perspective on flavonoids as the transcriptional effectors of ARHDs, highlighting the significant variability of these enzymes and the divergent responses that they elicit. Moreover, our results contribute to understanding the complex interactions between microorganisms and SPMs and provide insights into the molecular basis of a number of them.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"11 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global phylogenomic analysis of <i>Staphylococcus pseudintermedius</i> reveals genomic and prophage diversity in multidrug-resistant lineages.","authors":"Lucy F Grist, Alice Brown, Noel Fitzpatrick, Giuseppina Mariano, Roberto M La Ragione, Arnoud H M Van Vliet, Jai W Mehat","doi":"10.1099/mgen.0.001369","DOIUrl":"10.1099/mgen.0.001369","url":null,"abstract":"<p><p><i>Staphylococcus pseudintermedius</i> is the foremost cause of opportunistic canine skin and mucosal infections worldwide. Multidrug-resistant (MDR) and methicillin-resistant <i>Staphylococcus pseudintermedius</i> (MRSP) lineages have disseminated globally in the last decade and present significant treatment challenges. However, little is known regarding the factors that contribute to the success of MDR lineages. In this study, we compared the genome sequence of 110 UK isolates of <i>S. pseudintermedius</i> with 2166 genomes of <i>S. pseudintermedius</i> populations from different continents. A novel core genome multi-locus typing scheme was generated to allow large-scale, rapid and detailed analysis of <i>S. pseudintermedius</i> phylogenies and was used to show that the <i>S. pseudintermedius</i> population structure is broadly segregated into an MDR population and a non-MDR population. MRSP lineages are predicted to encode certain resistance genes either chromosomally or on plasmids, and this is associated with their MLST sequence type. A comparison of lineages most frequently implicated in disease, ST-45 and ST-71, with the phylogenetically related ST-496 lineage that has a comparatively low disease rate, revealed that ST-45 and ST-71 genomes encode distinct combinations of phage-defence systems and concurrently encode a high number of intact prophages. In contrast, ST-496 genomes encode a wider array of phage defence systems and lack intact and complete prophages. These findings indicate that MRSP lineages have significant structural genomic differences and that prophage integration and differential antiviral systems correlate with the emergence of successful genotypes.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"11 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"microGWAS: a computational pipeline to perform large-scale bacterial genome-wide association studies.","authors":"Judit Burgaya, Bamu F Damaris, Jenny Fiebig, Marco Galardini","doi":"10.1099/mgen.0.001349","DOIUrl":"10.1099/mgen.0.001349","url":null,"abstract":"<p><p>Identifying genetic variants associated with bacterial phenotypes, such as virulence, host preference and antimicrobial resistance, has great potential for a better understanding of the mechanisms involved in these traits. The availability of large collections of bacterial genomes has made genome-wide association studies (GWAS) a common approach for this purpose. The need to employ multiple software tools for data pre- and postprocessing limits the application of these methods by experienced bioinformaticians. To address this issue, we have developed a pipeline to perform bacterial GWAS from a set of assemblies and annotations, with multiple phenotypes as targets. The associations are run using five sets of genetic variants: unitigs, gene presence/absence, rare variants (i.e. gene burden test), gene-cluster-specific <i>k</i>-mers and all unitigs jointly. All variants passing the association threshold are further annotated to identify overrepresented biological processes and pathways. The results can be further augmented by generating a phylogenetic tree and predicting the presence of antimicrobial resistance and virulence-associated genes. We tested the microGWAS pipeline on a previously reported dataset on <i>Escherichia coli</i> virulence, successfully identifying the causal variants and providing further interpretation of the association results. The microGWAS pipeline integrates state-of-the-art tools to perform bacterial GWAS into a single, user-friendly and reproducible pipeline, allowing for the democratization of these analyses. The pipeline, together with its documentation, can be accessed at https://github.com/microbial-pangenomes-lab/microGWAS.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"11 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: An updated catalogue of diverse type II polyketide synthase biosynthetic gene clusters captured from large-scale nucleotide databases.","authors":"Christina M McBride, Eric L Miller, Louise K Charkoudian","doi":"10.1099/mgen.0.001348","DOIUrl":"10.1099/mgen.0.001348","url":null,"abstract":"","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"11 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Chlamydia trachomatis</i> genomes from rectal samples: description of a new clade comprising <i>ompA</i>-genotype L4 from Argentina.","authors":"Karina Andrea Büttner, Fanny Wegner, Vera Bregy, Andrea Carolina Entrocassi, María Lucía Gallo Vaulet, Deysi López Aquino, Luciana La Rosa, Laura Svidler López, Mirja H Puolakkainen, Eija Hiltunen-Back, Frank Imkamp, Adrian Egli, Helena M B Seth-Smith, Marcelo Rodríguez Fermepin, On Behalf Of The Escmid Study Group For Mycoplasma And Chlamydia Infections Esgmac","doi":"10.1099/mgen.0.001350","DOIUrl":"10.1099/mgen.0.001350","url":null,"abstract":"<p><p>Whole-genome analysis has provided insights into the evolution of <i>Chlamydia trachomatis</i> and, recently, into circulating strains that cause lymphogranuloma venereum (LGV). A large LGV outbreak of a new <i>ompA</i>-genotype, L2b, was first reported in Europe in the early 2000s, primarily affecting men who have sex with men (MSM), and then expanded globally. More recent work shows that this outbreak is diversifying into variants of described <i>ompA</i>-genotypes, with the same L2b genomic backbone. This study extends the investigation of LGV cases to Argentina and Finland. In 2017, an LGV outbreak was described in Argentina characterized by distinct genomic features shown by both <i>ompA</i>-genotyping and Multi-Locus Sequence Typing (MLST) analysis. We have obtained whole-genome sequences from cultured isolates and clinical samples via SureSelect (Agilent) target enrichment. Based on <i>ompA</i> and phylogenetic analyses, we describe further diversity within the <i>ompA</i>-genotype L2b clade, illustrating the transmission dynamics in Argentina and Finland. A key finding is that of a novel clade of Argentinian samples, characterized by a proposed new <i>ompA</i>-genotype L4. Additionally, we present the genome sequence of a non-LGV strain associated with anorectal proctitis. These findings contribute to the investigation of LGV evolution, particularly with the presence of the novel L4 lineage, and provide insights into genomic diversity and transmission dynamics of <i>C. trachomatis</i>.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"11 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic and genetic heterogeneity of <i>Acinetobacter baumannii</i> in the course of an animal chronic infection.","authors":"Léa Bednarczuk, Alexandre Chassard, Julie Plantade, Xavier Charpentier, Maria-Halima Laaberki","doi":"10.1099/mgen.0.001352","DOIUrl":"10.1099/mgen.0.001352","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> is a nosocomial pathogen associated with various infections, including urinary tract infections (UTIs). In the course of an infection, <i>A. baumannii</i> is known to rapidly become resistant to antibiotic therapy, but much less is known about possible adaptation without antibiotic pressure. Through a retrospective study, we investigated within-host genetic diversity during a subclinical 5-year UTI in an animal-patient after withdrawal of colistin treatment. We conducted whole-genome sequencing and phenotypic assays on 17 clonally related isolates from the Sequence Type 25 lineage. Phylogenomic analysis revealed their proximity with animal and human strains from the same country suggesting zoonotic transmission (France). In this case study, the clonally related strains presented variations in genome sizes and nucleotide sequences. Over the course of the infection, <i>A. baumannii</i> underwent genome reduction through insertion sequence (IS) recombination, phage excision or plasmid curing. Alongside this global genome reduction, we observed an expansion of IS<i>17</i>, initially located on the endogenous large plasmid. Genetic variations were mainly located in biofilm formation and metabolism genes. We observed repeated variations affecting three biofilm genes and two adhesion operons associated with weak biofilm-forming capacity. Conversely, only two metabolic genes were recurrently affected, and phenotypic assays indicated a rather stable metabolism profile between the isolates suggesting minor adaptations to its host. Lastly, an overall decreased antibiotic resistance - expected in the absence of antibiotic treatment - contrasted with a conserved colistin resistance due to a <i>pmrB</i> mutation among the isolates.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"11 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic diversity and evolutionary patterns of <i>Edwardsiella ictaluri</i> affecting farmed striped catfish (<i>Pangasianodon hypophthalmus</i>) in Vietnam over 20 years.","authors":"Christopher J Payne, Vo Hong Phuong, Nguyen Ngoc Phuoc, Tu Thanh Dung, Le Hong Phuoc, Margaret Crumlish","doi":"10.1099/mgen.0.001368","DOIUrl":"10.1099/mgen.0.001368","url":null,"abstract":"<p><p><i>Edwardsiella ictaluri</i> continues to pose a significant risk to the health and production of striped catfish (<i>Pangasianodon hypophthalmus</i>) in Vietnam. Whilst recent advances in genomic sequencing provide an insight into the global genomic diversity of this important fish pathogen, genome-wide analysis of Vietnamese isolates recovered over time is lacking. In this study, we used a whole-genome sequencing approach to compare the genomes of 31 <i>E. ictaluri</i> isolates recovered over a 20-year period (2001-2021) and performed comparative genomic analysis to explore temporal changes in genome diversity, population structure and mechanisms driving pathogenesis and antimicrobial resistance. Our findings revealed an open pan-genome with 4148 genes and a core genome (3 060 genes) accounting for over two-thirds of the genome. Moreover, we found the genomes sequenced to classify into two distinct lineages and estimated the ancestral origin of these lineages within Vietnam to date back to the 1950s. Plasmids were highly prevalent in Vietnamese <i>E. ictaluri</i>, with isolates harbouring up to four plasmids within their genome. Further, a diverse mobilome was observed with nine different plasmid types detected across the genome collection. Exploration of putative plasmids revealed a diverse set of antimicrobial resistance genes (ARGs) against key antibiotics used in Vietnamese aquaculture and virulence genes associated with protein secretion systems. Correlation analysis revealed the total number of ARGs detected in genomes to increase with isolate recovery time. Whilst the number of virulence genes remained relatively stable, temporal variation was noted in several virulence factors related to motility and immune system modulation. Findings from this study highlight the need for continued genomic surveillance to monitor changes in antimicrobial resistance and pathogenesis, to help inform the development of disease control and management strategies.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"11 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutations in the riboflavin biosynthesis pathway confer resistance to furazolidone and abolish the synergistic interaction between furazolidone and vancomycin in <i>Escherichia coli</i>.","authors":"Hannah Wykes, Vuong Van Hung Le, Jasna Rakonjac","doi":"10.1099/mgen.0.001356","DOIUrl":"10.1099/mgen.0.001356","url":null,"abstract":"<p><p>The combined application of furazolidone and vancomycin has previously been shown to be synergistic against Gram-negative pathogens, with great therapeutic promise. However, the emergence and mechanism of resistance to this antibiotic combination have not been characterized. To fill this gap, we here selected <i>Escherichia coli</i> progeny for growth on the furazolidone-vancomycin combination at the concentration where the parent was sensitive. We show that selected clones were associated with increased resistance to neither, only one drug, or both furazolidone and vancomycin, but in all cases were associated with a decrease in the growth inhibition synergy. Using whole-genome sequencing, we identified various gene mutations in the resistant mutants. We further investigated the mechanism behind the most frequently arising mutations, those in the riboflavin biosynthesis genes <i>ribB</i> and <i>ribE</i>, that represent novel mutations causing furazolidone resistance and diminished vancomycin-furazolidone synergy. It was found that these <i>ribB/ribE</i> mutations act predominantly by decreasing the activity of the NfsA and NfsB nitroreductases. The emergence of the <i>ribB</i>/<i>ribE</i> mutations imposes a significant fitness cost on bacterial growth. Surprisingly, supplementing the medium with riboflavin, which compensates for the affected riboflavin biosynthesis pathway, could restore the normal growth of the <i>ribB</i>/<i>ribE</i> mutants while having no effects on the furazolidone resistance phenotype. Searching the <i>ribB/ribE</i> mutations in the public sequencing database detects the presence of the furazolidone-resistance-conferring <i>ribE</i> mutations (TKAG^131-134 deletion or duplication) in clinical isolates from different countries. Hypotheses explaining why these <i>ribE</i> mutations were found in clinical isolates despite having poor fitness were further discussed.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"11 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}