Icíar Rodríguez-Avial, Sthefany Torres, Yuri Puglla, Laura Pérez-Martín, Juan-Luis Sebastianes, Alberto Delgado-Iribarren, Esther Culebras, María-José Valderrama
{"title":"Repurposing insights: experimental and pharmacological approach on L-captopril and dimercaprol as metallo-β-lactamase inhibitors.","authors":"Icíar Rodríguez-Avial, Sthefany Torres, Yuri Puglla, Laura Pérez-Martín, Juan-Luis Sebastianes, Alberto Delgado-Iribarren, Esther Culebras, María-José Valderrama","doi":"10.1093/femsle/fnag064","DOIUrl":"10.1093/femsle/fnag064","url":null,"abstract":"<p><p>The design of specific inhibitors of metallo-β-lactamases (MBL) is one of the priority research lines due to the spread of carbapenem resistant bacterial strains which limits therapeutic options. In parallel, the investigation of new uses of known medicines is prompted by regulatory agencies. In this work, the potential MBL inhibitory potency of L-captopril (an antihypertensive drug) and dimercaprol (used in poisoning by metals) was investigated in a clinical collection of Enterobacterales and Pseudomonas spp. In addition, a comprehensive review of the available literature was conducted, to discuss jointly new and previously available data. The results indicate that activity of imipenem and meropenem combined with 400 mg/l is restored for > 80% and 60%, respectively, for Enterobacterales strains, but not in the Pseudomonas group. Dimercaprol had a limited activity in both bacterial groups. Based on these promising results of L-captopril, pharmacological calculations were performed. It is concluded that the repurposing objective could not be achieved as the overall data indicated that the concentrations of captopril required to achieve carbapenemase inhibitory activity in vivo are higher than maximum used in treatment. Communication of negative results would help to discontinue active current research on L-captopril and should focus on other potential MBL inhibitors.</p>","PeriodicalId":12214,"journal":{"name":"Fems Microbiology Letters","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13261764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuqing Sun, Yu Wang, Caopei Zheng, Li Han, Yulin Zhang
{"title":"Exosomes in pulmonary infection: mediators of immune regulation and potential immunotherapeutic targets.","authors":"Yuqing Sun, Yu Wang, Caopei Zheng, Li Han, Yulin Zhang","doi":"10.1093/femsle/fnag017","DOIUrl":"10.1093/femsle/fnag017","url":null,"abstract":"<p><p>Pulmonary infection is one of the major health problems worldwide, with common pathogens including viruses, bacteria, and fungi. During pulmonary infection, exosomes secreted by different immune cells serve as important communication mediators between cells and have the ability to regulate the immune system. Exosomes regulate lung immune responses by carrying bioactive molecules, including miRNA, proteins, and lipids, initiating and inhibiting inflammatory responses, pathogen clearance, and immune tolerance. This paper discusses multiple roles of exosomes in regulating the function of lung-resident innate immune cells (epithelial cells, macrophages, and neutrophils) and their potential effects in infectious diseases of the lung. In addition, the existing research has described the prospects of exosomes in immunotherapy. This review aims to summarise their role in the diagnosis and treatment of pulmonary infection in order to clarify the role and mechanism of exosomes in pulmonary infectious diseases.</p>","PeriodicalId":12214,"journal":{"name":"Fems Microbiology Letters","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CRISPR-Cas gene editing technology in biomanufacturing to enhance stress tolerance of microbial strains.","authors":"Hongmin Zhang, Lerong Liu, Dingkang Wang, Xinya Yang, Yiting Kang, Jing Huang, Yuanshuo Ouyang, Hongfei Yu, Yongjie Zhang","doi":"10.1093/femsle/fnag030","DOIUrl":"10.1093/femsle/fnag030","url":null,"abstract":"<p><p>In response to the loss of microbial efficiency caused by environmental stress in biomanufacturing, CRISPR-Cas gene editing technology has become a core tool for enhancing stress tolerance by accurately targeting genomic loci. This article systematically reviews the progress of its application. By optimizing engineered nucleases, gRNA design, and innovative delivery strategies, this technology successfully regulates key pathways in oxidative stress responses. It integrates functional genome screening with dynamic regulation to examine the networks of multi-gene collaborative tolerance. In the construction of high-stress-tolerant industrial chassis cells, the stress survival rate (>90% in Bacillus subtilis under thermal stress) and product synthesis ability (such as cellulose producing ethanol up to 4.5 g/l) of strains such as Escherichia coli and Corynebacterium glutamicum were significantly improved. Current challenges focus on delivery efficiency, off-target risks, and complex regulatory bottlenecks. In the future, the development of new editing tools and intelligent circuits will promote their industrial application in sustainable biomanufacturing.</p>","PeriodicalId":12214,"journal":{"name":"Fems Microbiology Letters","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Beatriz Reis Alvaro da Silva, Amanda Vieira de Barros, Bruna Rodrigues de Sousa, Milena Danda Vasconcelos Santos, Carem Tavares Pessoa Mendes, Steffany Ghlende Gomes Chaves, Bruno Oliveira de Veras, Reginaldo Gonçalves de Lima Neto, Oscar Felipe Fonseca de Brito, Henrique Douglas Melo Coutinho, Maria Betânia Melo de Oliveira
{"title":"Antibacterial activity of geraniol in prevalent and resistant bacteria of the oral microbiota of patients.","authors":"Beatriz Reis Alvaro da Silva, Amanda Vieira de Barros, Bruna Rodrigues de Sousa, Milena Danda Vasconcelos Santos, Carem Tavares Pessoa Mendes, Steffany Ghlende Gomes Chaves, Bruno Oliveira de Veras, Reginaldo Gonçalves de Lima Neto, Oscar Felipe Fonseca de Brito, Henrique Douglas Melo Coutinho, Maria Betânia Melo de Oliveira","doi":"10.1093/femsle/fnag085","DOIUrl":"10.1093/femsle/fnag085","url":null,"abstract":"<p><p>Dysbiotic diseases of the oral microbiota, such as dental caries, endodontic infections, and periodontitis, represent a clinical challenge due to bacterial resistance and biofilm formation. In this context, plant-derived secondary metabolites such as Geraniol have emerged as promising alternatives owing to their low toxicity and multiple mechanisms of action. This study aimed to evaluate the antibacterial and antibiofilm activity of Geraniol against resistant and prevalent bacterial species from the oral microbiota of patients treated at the Dental Clinic of the Federal University of Pernambuco (UFPE). Samples were collected from patients with oral alterations, and microorganisms were identified using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using the VITEK® automated system. Multidrug-resistant (MDR) isolates and reference strains were selected to assess the minimum inhibitory concentration (MIC), minimum bactericidal concentration, and antibiofilm activity of Geraniol. A total of 74 isolates were identified, including Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, and Pseudomonas stutzeri, with 60% classified as MDR. Geraniol exhibited significant inhibitory activity against Streptococcus mutans (ATCC 700610) and Enterococcus faecalis (ATCC 29212), with an MIC of 0.032 mg/ml. Furthermore, Geraniol inhibited biofilm formation in six isolates of S. mutans and E. faecalis. These findings highlight the potential of Geraniol as a therapeutic alternative for resistant oral infections, particularly in dysbiosis-associated biofilms. Future studies should explore its clinical applications and potential combinations with other agents to overcome bacterial resistance and improve outcomes in the treatment of oral diseases.</p>","PeriodicalId":12214,"journal":{"name":"Fems Microbiology Letters","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Phenotypic profiling of carbon utilization of Pectobacterium brasiliense (Pbr1692).","authors":"","doi":"10.1093/femsle/fnag025","DOIUrl":"10.1093/femsle/fnag025","url":null,"abstract":"","PeriodicalId":12214,"journal":{"name":"Fems Microbiology Letters","volume":"373 ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lineage-specific remodeling of a conserved tRNA-Thr-associated genomic island in Edwardsiella anguillarum.","authors":"Shogo Harakawa, Hidemasa Kawakami, Shin-Ichi Kitamura, Naritoyo Ishibashi, Shuntaro Watanabe, Tohru Mekata","doi":"10.1093/femsle/fnag119","DOIUrl":"10.1093/femsle/fnag119","url":null,"abstract":"<p><p>Edwardsiella anguillarum is a bacterial pathogen affecting diverse aquaculture species worldwide, including red seabream, Japanese eel, and tilapia. In Japan, strains show a phenotypic dichotomy, where red seabream-derived strains are non-motile and ornithine decarboxylase (ODC)-negative, whereas eel-derived strains retain both traits. However, the evolutionary processes underlying lineage diversification within this species remain poorly understood. We performed a global comparative genomic analysis of 24 E. anguillarum strains, including seven newly sequenced genomes from Japan. Despite high ANI values (>99.6%), SNP analysis revealed lineage-level divergence, with 6500-7500 SNPs separating red seabream-associated and eel-associated lineages. Comparative analysis identified a conserved chromosomal hotspot adjacent to the tRNA-Thr gene with lineage-specific structural variation. The Japanese red seabream-associated lineage possessed a compact ∼10-kb region containing a Type I-E CRISPR/Cas system, whereas eel-associated and tilapia-derived strains carried expanded genomic islands (∼48-52 kb) enriched in DNA repair and mobile genetic element functions. These configurations were associated with phylogeographic lineages. Genes associated with motility and ODC activity were conserved across lineages, with no evidence of gene loss or major structural disruption. Phylogenetic analysis of the island-associated tyrosine-type recombinase/integrase (YR) was broadly consistent with the core genome. A shared frameshift mutation in eel- and tilapia-derived strains was consistent with a shared pseudogenization event. Overall, our findings indicate that diversification in E. anguillarum is associated with localized structural variation at a conserved tRNA-Thr-associated chromosomal hotspot within an otherwise highly conserved core genome.</p>","PeriodicalId":12214,"journal":{"name":"Fems Microbiology Letters","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Najeeb, Sara Matthews, Michèle Prévost, Sebastien P Faucher
{"title":"Comparative genomic analysis reveals distinct population structure in Legionella anisa.","authors":"Maria Najeeb, Sara Matthews, Michèle Prévost, Sebastien P Faucher","doi":"10.1093/femsle/fnag100","DOIUrl":"10.1093/femsle/fnag100","url":null,"abstract":"<p><p>Legionella anisa has been frequently isolated from engineered water systems; however, its population structure remains understudied compared to Legionella pneumophila. Here, we generated complete genome sequences for four L. anisa isolates recovered from a healthcare facility in Rimouski, Canada. Further the population structure of this species was investigated by performing comparative genomic analyses of the genomes generated in this study together with publicly available L. anisa genomes. Genome-wide phylogenetic analysis revealed the presence of three distinct clades separated by substantial genetic divergence (∼500 single nucleotide polymorphisms), with the Rimouski isolates forming a tightly clustered group, suggesting a clonal lineage. Comparative pangenome analysis indicated moderate core genome conservation accompanied by a highly variable accessory genome (∼50%). The isolates characterized in this study harbored multiple plasmids encoding genes associated with conjugation, heavy metal resistance, and other stress-related functions, suggesting potential roles in environmental persistence. Previous studies have shown that L. anisa can proliferate within protozoan host cells, although outcomes vary depending on the host species. Our isolates showed efficient proliferation within Acanthamoeba castellanii, but not within Vermamoeba vermiformis, under the conditions tested. Together, these findings underscore the genomic diversity of this understudied Legionella species and provide a framework for future investigations regarding environmental persistence and potential pathogenicity.</p>","PeriodicalId":12214,"journal":{"name":"Fems Microbiology Letters","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxin-antitoxin systems propagate through addictive selection during bacterial chromosome-plasmid conflicts.","authors":"Pavithra Anantharaman Sudhakari, Bhaskar Chandra Mohan Ramisetty","doi":"10.1093/femsle/fnag021","DOIUrl":"10.1093/femsle/fnag021","url":null,"abstract":"<p><p>Plasmids are obligate genetic parasites that significantly influence bacterial host adaptation, ecology, and clinically relevant traits such as antibiotic resistance. They persist within host populations primarily through self-maintenance mechanisms, most notably Toxin-Antitoxin (TA) systems, which are autoregulated poison-antidote operons mediating genomic conflict. Plasmid-encoded TAs act as \"addiction modules,\" promoting plasmid stability via post-segregational killing of daughter cells that fail to inherit the plasmid. However, the widespread and abundant presence of TAs on bacterial chromosomes remains an evolutionary puzzle. We conducted comprehensive bioinformatics analyses of 11 000 bacterial chromosomes and 1300 plasmids, focusing on Type II TAs in Escherichia and Shigella species, to elucidate their prevalence, distribution, and ecological significance. Our results reveal distinct horizontal gene transfer patterns and strongly support the antiaddiction hypothesis, which posits that chromosomal TAs protect host cells by neutralizing TA-plasmid addiction effects. This neutralization allows for plasmid loss without the toxin-mediated lethal consequences, resulting in a pattern of mutual exclusivity between identical chromosomal and plasmid TAs. This study reinforces the view that chromosomal Type II TA systems play a significant role in counteracting addiction processes within bacterial chromosomes.</p>","PeriodicalId":12214,"journal":{"name":"Fems Microbiology Letters","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Affinity between gut microbiota and ankylosing spondylitis: insight from causal analysis.","authors":"Zengkun Li, Jianying Pei, Jiangwen Ruan, Hongwang Cui, Shicheng Li, Tongmeng Jiang","doi":"10.1093/femsle/fnag016","DOIUrl":"10.1093/femsle/fnag016","url":null,"abstract":"<p><p>Ankylosing spondylitis (AS) is a chronic inflammatory disease with a global prevalence, primarily affecting the axial skeleton. While traditional therapies are often employed before surgical interventions, pharmacotherapy is typically reserved for cases of unstable AS condition. The gut microbiota has been implicated in numerous pathological conditions. However, its specific role in AS remains poorly understood. To address this knowledge gap, we applied Mendelian randomization (MR) to explore potential causal relationships between gut microbiota and AS. For this analysis, we utilized two large-scale genome-wide association study datasets: one comprising 18 340 individuals across 24 cohorts for human gut microbiota, and another consisting of 9069 AS cases and 1550 controls for AS susceptibility. Following heterogeneity testing, assessment of horizontal pleiotropy and application of multiple MR methods and 'leave-one-out' analysis, we identified 10 bacterial traits associated with AS risk. These include four risk-increasing factors: Actinobacteria (class), Streptococcaceae (family), Enterorhabdus (genus), and the Ruminococcaceae NK4A214 group (genus); and six risk-decreasing factors: Lactobacillaceae (family), Rikenellaceae (family), Anaerotruncus (genus), Eubacterium oxidoreducens group (genus), Howardella (genus), and Oscillibacter (genus). This study provides novel insights into the gut-spine axis and suggests potential avenues for AS management through microbiota-targeted interventions.</p>","PeriodicalId":12214,"journal":{"name":"Fems Microbiology Letters","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fumiaki Mori, Ann G Dunlea, Tatsuhiko Hoshino, Erika Tanaka, Kazutaka Yasukawa, Takeshi Terada, Yuki Morono
{"title":"Sedimentary hiatus causes abrupt decline and shifts in marine subsurface sediment microbial communities: a study from IODP Exp. 378 Site U1553 offshore southern New Zealand.","authors":"Fumiaki Mori, Ann G Dunlea, Tatsuhiko Hoshino, Erika Tanaka, Kazutaka Yasukawa, Takeshi Terada, Yuki Morono","doi":"10.1093/femsle/fnag058","DOIUrl":"10.1093/femsle/fnag058","url":null,"abstract":"<p><p>Hiatuses within marine sediment are discontinuities in stratigraphic sediment records, forming adjacent layers of different ages. To evaluate how such discontinuities relate to subsurface microbial distribution, we examined microbial cell abundance and 16S rRNA gene-based community structure along a sediment core from International Ocean Discovery Program Expedition 378 Site U1553 (offshore southern New Zealand). Cell abundances decreased logarithmically with depth but showed two step-like declines: a sharp drop across a major hiatus at ∼4 mbsf and a second decline at ∼21.5-25 mbsf that overlaps, within sampling resolution, a reported Mn-Fe transition in porewater chemistry. Across the major hiatus, community composition and alpha diversity shifted markedly, indicating a persistent imprint of depositional discontinuity on subseafloor communities. Within the interval where community data were obtained (1.5-21.5 mbsf), community variation was more strongly associated with sediment depth and age than with the measured porewater solutes. These observations highlight stratigraphic age discontinuities as important contextual features for interpreting subseafloor microbial biomass and community patterns.</p>","PeriodicalId":12214,"journal":{"name":"Fems Microbiology Letters","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13234949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}