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PubMed2024

Contaminant-degrading bacteria are super carriers of antibiotic resistance genes in municipal landfills: A metagenomics-based study.

Municipal landfills are hotspot sources of antimicrobial resistance (AMR) and are also important habitats of contaminant-degrading bacteria. However, high diversity of antibiotic resistance genes (ARGs) in landfills hinders assessing AMR risks in the affected environment. More concerned, whether there is co-selection or enrichment of antibiotic-resistant bacteria and contaminant-degrading bacteria in these extremely polluted environments is far less understood. Here, we collected metagenomic datasets of 32 raw leachate and 45 solid waste samples in 22 municipal landfills of China. The antibiotic resistome, antibiotic-resistant bacteria and contaminant-degrading bacteria were explored, and were then compared with other environmental types. Results showed that the antibiotic resistome in landfills contained 1,403 ARG subtypes, with the total abundance over the levels in natural environments and reaching the levels in human feces and sewage. Therein, 49 subtypes were listed as top priority ARGs for future surveillance based on the criteria of enrichment in landfills, mobilizable and present in pathogens. By comparing to those in less contaminated river environments, we elucidated an enrichment of antibiotic-resistant bacteria with contaminant-degrading potentials in landfills. Bacteria in Pseudomonadaceae, Moraxellaceae, Xanthomonadaceae and Enterobacteriaceae deserved the most concerns since 72.2 % of ARG hosts were classified to them. Klebsiella pneumoniae, Acinetobacter nosocomialis and Escherichia coli were abundant multidrug-resistant pathogenic species in raw leachate (∼10.2 % of total microbiomes), but they rarely carried contaminant-degradation genes. Notably, several bacterial genera belonging to Pseudomonadaceae had the most antibiotic-resistant, pathogenic, and contaminant-degrading potentials than other bacteria. Overall, the findings highlight environmental selection for contaminant-degrading antibiotic-resistant pathogens, and provide significant insights into AMR risks in municipal landfills.

Metagenomics↗
PubMed2025

Unveiling the mechanism of micro-and-nano plastic phytotoxicity on terrestrial plants: A comprehensive review of omics approaches.

Micro-and-nano plastics (MNPs) are pervasive in terrestrial ecosystems and represent an increasing threat to plant health; however, the mechanisms underlying their phytotoxicity remain inadequately understood. MNPs can infiltrate plants through roots or leaves, causing a range of toxic effects, including inhibiting water and nutrient uptake, reducing seed germination rates, and impeding photosynthesis, resulting in oxidative damage within the plant system. The effects of MNPs are complex and influenced by various factors including size, shape, functional groups, and concentration. Recent advancements in omics technologies such as proteomics, metabolomics, transcriptomics, and microbiomics, coupled with emerging technologies like 4D omics, phenomics, spatial transcriptomics, and single-cell omics, offer unprecedented insight into the physiological, molecular, and cellular responses of terrestrial plants to MNPs exposure. This literature review synthesizes current findings regarding MNPs-induced phytotoxicity, emphasizing alterations in gene expression, protein synthesis, metabolic pathways, and physiological disruptions as revealed through omics analyses. We summarize how MNPs interact with plant cellular structures, disrupt metabolic processes, and induce oxidative stress, ultimately affecting plant growth and productivity. Furthermore, we have identified critical knowledge gaps and proposed future research directions, highlighting the necessity for integrative omics studies to elucidate the complex pathways of MNPs toxicity in terrestrial plants. In conclusion, this review underscores the potential of omics approaches to elucidate the mechanisms of MNPs-phytotoxicity and to develop strategies for mitigating the environmental impact of MNPs on plant health.

Plants↗
PubMed2024

Metagenomic analysis reveals gene taxonomic and functional diversity response to microplastics and cadmium in an agricultural soil.

Both microplastics (MPs) and heavy metals are common soil pollutants and can interact to generate combined toxicity to soil ecosystems, but their impact on soil microbial communities (e.g., archaea and viruses) remains poorly studied. Here, metagenomic analysis was used to explore the response of soil microbiome in an agricultural soil exposed to MPs [i.e., polyethylene (PE), polystyrene (PS), and polylactic acid (PLA)] and/or Cd. Results showed that MPs had more profound effects on microbial community composition, diversity, and gene abundances when compared to Cd or their combination. Metagenomic analysis indicated that the gene taxonomic diversity and functional diversity of microbial communities varied with MPs type and dose. MPs affected the relative abundance of major microbial phyla and genera, while their coexistence with Cd influenced dominant fungi and viruses. Nitrogen-transforming and pathogenic genera, which were more sensitive to MPs variations, could serve as the indicative taxa for MPs contamination. High-dose PLA treatments (10%, w/w) not only elevated nitrogen metabolism and pathogenic genes, but also enriched copiotrophic microbes from the Proteobacteria phylum. Overall, MPs and Cd showed minimal interactions on soil microbial communities. This study highlights the microbial shifts due to co-occurring MPs and Cd, providing evidence for understanding their environmental risks.

Soil Microbiology↗
PubMed2026

Enrichment of Lysobacter in a long-term organically managed agricultural field with low soilborne disease incidence.

Disease-suppressive soils, in which soilborne pathogens are naturally suppressed, offer a promising model for sustainable crop protection, particularly in organic farming systems where chemical disease control options are limited. Although disease suppression in these soils is considered to rely on biological control, the underlying mechanisms remain poorly understood. In this study, we investigated soil from a long-term organically managed field in Shiga Prefecture, Japan, where soilborne disease incidence has remained consistently low, to identify bacterial community features potentially associated with this field. The 16S rRNA gene amplicon sequencing indicated that this soil harbored a bacterial community distinct from those of nearby agricultural soils. Following the application of organic compounds, the genus Lysobacter, a taxon with known antagonistic activity against plant pathogens, was markedly enriched in response to proteinaceous organic inputs. This enrichment was consistent across sampling times and specific to certain proteinaceous organic inputs, whereas minimal effects were observed on chitin, N-acetyl-d-glucosamine, or cysteine. Broader soil surveys indicated that Lysobacter enrichment was not strictly associated with whether soils had been managed under organic or conventional farming practices. Stepwise multiple regression analysis identified 10 co-occurring bacterial genera that were strongly associated with Lysobacter abundance. These findings highlight condition-dependent Lysobacter enrichment as a characteristic microbial response to proteinaceous organic amendments in this low-disease-incidence field and provide microbial insights that may inform microbiome-based strategies for sustainable soil management.

Lysobacter↗
PubMed2026

Quantifying the aromatic amino acid metabolome: UPLC-MS/MS analysis of aromatic amino acids and their host and co-metabolites in plasma.

Aromatic amino acids (AAAs), tryptophan, phenylalanine, and tyrosine along with their pathway metabolites have been implicated in the pathogenesis of diseases ranging from cardiovascular, neurological, inflammatory, and cancer diseases, among others. As such, the measurement of the primary AAAs, their host pathway metabolites, and microbiome derived co-metabolites in blood can provide a sensitive reflection of systemic health. The aim of the study was to develop a method for the quantification of 17 metabolites, the three AAAs and various of their metabolites in plasma using a high-throughput ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The method demonstrated a dynamic range (1 to 16,700 ng/mL), with detection limits (LOD) as low as 0.05 ng/mL. Quantification limits ranged from 3 to 5019 ng/mL (LLOQ) and up to 16,700 ng/mL (ULOQ). Recovery at LQC, MQC, and HQC was satisfactory and consistent across most metabolites, with significant matrix effects observed only for 4-ethylphenol sulfate. Furthermore, intra and inter-day accuracy and precision met all acceptance criteria at all quality control concentrations for most of the metabolites. Measurement of NIST SRM 1950 showcased the method's accuracy for most of the metabolites. Finally, the method was applied on the analysis of plasma samples from 55 individuals (13 males and 42 females) providing information on AAAs and their pathway metabolites relevant concentrations in human plasma.

Amino Acids, Aromatic↗
PubMed2026

Global lessons from antibiotic resistance: Metformin-hydrolysing genes in transposable elements, a new threat for type II diabetic patients?

OBJECTIVES: To investigate the evolutionary origin, genomic mobility, and potential dissemination of metformin-hydrolysing genes (mfmAB), and to assess whether environmental selection by metformin pollution may drive the emergence of transferable pharmaceutical-degrading traits analogous to antibiotic resistance. METHODS: Large-scale comparative genomics was performed using publicly available bacterial genomes carrying mfmAB homologs. Phylogenomic reconstruction, average nucleotide identity analysis, genomic context comparison, plasmid characterization, and insertion sequence mapping were used to infer evolutionary history and identify mechanisms of horizontal gene transfer. RESULTS: mfmAB homologs were identified in twelve Aminobacter and three Pseudomonas genomes within a conserved ∼8.2 kb gene cluster. Phylogenomic analyses showed that metformin-degrading capacity emerged independently in multiple Aminobacter lineages across distinct continents, consistent with convergent evolution under anthropogenic selective pressure. Genomic comparisons indicated a chromosomal origin of mfmAB, followed by mobilization onto conjugative plasmids through IS1182-mediated transposition. In Pseudomonas, additional IS3/IS6-mediated transposition events integrated mfmAB into diverse plasmid backbones, frequently within composite transposons also encoding guanylurea and biguanide degradation pathways (guuH, bguH). These findings reveal a dynamic modular assembly of metabolic functions facilitating adaptation to pharmaceutical pollutants. CONCLUSIONS: Metformin pollution appears to promote the emergence and mobilization of pharmaceutical-degrading genes through mechanisms paralleling antibiotic resistance evolution. Although no clinical impact has yet been demonstrated, the potential spread of such genes into human-associated microbiomes and their possible co-selection with antibiotic resistance determinants represent an emerging One Health concern. Environmental surveillance of pharmaceutical-degrading genes is warranted to anticipate future threats to drug efficacy.

Convergent evolution↗
PubMed2026

Integrated immunoinformatics for the design of novel multi-epitope vaccine and identification of new drug targets against Stenotrophomonas maltophilia, a multidrug-resistant superbug.

BACKGROUND: Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen causing severe hospital-acquired infections, especially in immunocompromised patients. The absence of an effective vaccine and rising antibiotic resistance underscore the need for novel interventions. This study employed an integrated reverse vaccinology and computational analyses to identify new immunogenic targets, design a multi-epitope vaccine (MEV), and propose potential drug targets. METHODS: A comprehensive immunoinformatics pipeline was employed to assess antigenicity, allergenicity, human similarity, and physicochemical properties of S. maltophilia proteins. Both B- and T-cell epitopes were screened; however, only the top B-cell epitopes were selected for MEV construction, given the extracellular nature of S. maltophilia. MEV-TLR interactions were analyzed through molecular docking and dynamics simulations. In parallel, cytoplasmic proteins were screened via a subtractive genomics approach to identify essential, non-human homologous, and non-microbiome-similar proteins, which were further evaluated for druggability and interaction networks to propose novel therapeutic targets. RESULTS: From a total of 4111 proteins, seven potential immunogenic targets were identified: GspD (WP_108270537.1), FhuE (WP_049451370.1), fimbrial protein (WP_012479122.1), TonB-dependent receptor (WP_169448402.1), TolC family protein (WP_108270106.1), autotransporter beta-barrel OMP (WP_169448945.1), and a hypothetical protein (WP_005407892.1). Subsequently, an MEV was designed using five immunogenic epitopes derived from four of these targets: WP_005407892.1 (ADQDSSNM), WP_049451370.1 (SGKAEQ and GEESKTPS), WP_108270537.1 (GVTSTQSDSERT), and WP_169448945.1 (RELGGDRNE). Molecular docking and molecular dynamics simulations demonstrated strong, stable, and feasible interactions between the MEV and TLR-2 and TLR-4 receptors. Moreover, nine novel drug targets were predicted for S. maltophilia, providing new therapeutic insights. CONCLUSION: The designed MEV and identified immunogenic targets represent promising vaccine candidates against S. maltophilia. Further in vitro and in vivo studies are essential to confirm their safety, immunogenicity, and protective efficacy. Additionally, subtractive genomics analysis revealed nine novel, non-homologous drug targets, offering safer and more specific therapeutic avenues.

Drug targets↗
PubMed2026

Ancient DNA as a temporal lens: reconstructing evolution, migration, and disease dynamics.

Ancient DNA (aDNA) has transformed evolutionary biology and anthropology by providing direct, chronologically validated genetic evidence over millennia. This review synthesizes significant findings from the paleogenomic era (2010-2025), demonstrating how ancient DNA has resolved persistent debates across four interconnected themes: (i) human migration and admixture, revealing complex population transitions from archaic hominins to Holocene expansions; (ii) adaptation, tracking allele frequency changes during domestication and selection; (iii) pathogen history, clarifying the origins of pandemics and the evolution of microbiomes; and (iv) ecosystem dynamics, identifying extinction causes through sedimentary DNA and conservation genomics. We contend that scientific rigor and ethical stewardship are crucial for accurate conclusions, given ancient DNA study requires the destructive collection of culturally significant remains. This review argues that continued advancement will depend on the integration of genomic data with archaeological, isotopic, and proteomic evidence, and highlights the necessity for equitable involvement with descendant communities. By conceptualizing the past as a continuum of dynamic processes rather than static events, ancient DNA provides a revised historical narrative and insights relevant to contemporary concerns in conservation, health, and social justice.

Evolution↗
PubMed2026

Cooperative anaerobic catabolism of chlorinated organic compounds: implications for sustainable bioremediation.

Biodegradation research historically followed a reductionist approach focused on axenic (pure) cultures capable of catabolizing the specific contaminant(s) of interest. While this approach has substantially advanced our understanding of the microbiology, physiology, biochemistry, and genetics of contaminant degradation under laboratory conditions, it does not capture the complexity of natural and engineered environments. During in situ bioremediation, microbiomes are exposed to mixtures of contaminants, and microbial interactions profoundly influence contaminant transformation and fate. In anoxic environments, degradation of chlorinated compounds is often sustained by metabolic cooperation among taxonomically and physiologically distinct microorganisms. Through the exchange of metabolites such as hydrogen, formate, acetate, and other nutrients, microbial populations establish interdependent networks that overcome thermodynamic and physiological constraints, enabling self-sustaining systems of contaminant transformations that would be inefficient or impossible with individual organisms. We highlight examples of microbial interactions that underpin anaerobic catabolism of chlorinated contaminants, including systems resulting in self-sustained anaerobic bioremediation.

Biodegradation, Environmental↗
PubMed2026

Acetylcholine signaling regulates osmotic stress adaptation in the phytopathogen Dickeya solani.

Plants impose strong selective pressures that shape both the composition and functional potential of plant microbiomes. The adaptation of plant-associated bacteria to their hosts relies on an extensive repertoire of signal transduction systems that sense plant-derived molecules and dynamically adjust bacterial physiology and metabolism within the holobiont. These signals include key plant signaling compounds that regulate processes essential for plant-microbe interactions. Among them, acetylcholine is emerging as an important signaling molecule in both plants and bacteria. Here, we demonstrate that acetylcholine regulates the expression of the osmotic stress response betIBA gene cluster in the important phytopathogen Dickeya solani, where it plays an important role in osmoprotection. We show that the TetR-family transcriptional regulator associated with this pathway, BetIDs, recognizes acetylcholine as well as choline and trimethylamine. These three ligands differentially induce betIBA transcription in a manner that correlates with their binding affinities. Ligand binding does not affect BetIDs binding to the bet promoter or its oligomeric state. Instead, it induces pronounced changes in the secondary structure of BetIDs, with the magnitude of these conformational changes being ligand-dependent. We further show that quorum sensing modulates osmotic stress tolerance in D. solani by regulating the expression of the Bet pathway. The Bet system is required for the full virulence of D. solani, particularly in chemically complex plant tissues. Phylogenetic analyses reveal that the BetIBA system is widely distributed among plant-associated Pseudomonadota, collectively supporting its importance for bacterial survival and adaptation in plant-related environments.

Osmotic Pressure↗
PubMed2026

The current and future perspective of ChickenGTEx project and its applications in precision breeding.

The Chicken Genotype-Tissue Expression (ChickenGTEx) project was established to systematically characterize the regulatory landscape of the chicken genome and to accelerate the translation of functional genomics into precision breeding. By integrating whole-genome sequencing with multi-tissue transcriptomic profiling, ChickenGTEx provides a comprehensive atlas of gene expression regulation across diverse tissues and physiological systems. Current findings demonstrate that complex production traits are governed by coordinated regulatory networks rather than isolated loci, with substantial contributions from tissue-specific gene expression, structural variation, and genotype-by-sex interactions. Sex-dependent regulatory effects further refine the genetic architecture of metabolic, immune, and reproductive traits, highlighting the importance of incorporating sex as a biological variable in genomic analyses. Application of integrative omics frameworks within elite layer populations has revealed multilayer regulatory mechanisms underlying extended laying performance, feed efficiency, metabolic health, and eggshell quality. By partitioning phenotypic variance into genetic, regulatory, and host-microbiome components, these approaches move beyond association-based mapping toward causal inference and biological interpretation. Importantly, validated regulatory loci identified through ChickenGTEx and related analyses provide actionable markers for genomic selection and rational targets for precision genome modification. Looking forward, continued expansion of regulatory atlases, incorporation of single-cell and longitudinal data in diverse environmental conditions, and integration of functional annotation into breeding pipelines will further enhance prediction accuracy and sustainable genetic improvement. The ChickenGTEx project thus represents a foundational platform bridging functional genomics and practical poultry breeding.

Animals↗
PubMed2026

Multi-omics panorama of glaucoma: Pathogenesis, biomarkers, and novel therapeutic strategies.

Glaucoma is a group of irreversible, blinding eye diseases characterized by progressive loss of retinal ganglion cells, leading to gradual visual field defects that severely impact patients' quality of life. Its complex pathophysiological mechanisms remain incompletely understood, limiting the development of early diagnostic and effective therapeutic strategies. Advances in omics technologies have provided new insights into elucidating the pathophysiology of glaucoma. We summarize specific alterations in genomics, transcriptomics, proteomics, metabolomics, epigenomics, and microbiomics associated with glaucoma. We emphasize the systematic analysis of disease mechanisms, identification of clinically applicable biomarkers, and discovery of novel therapeutic targets through the integration of these data. This approach paves new pathways for glaucoma subtype diagnosis and personalized treatment, while also outlining future research directions and challenges.

Humans↗
PubMed2026

Host-virus dynamics in anaerobic digesters facing abiotic inhibition.

Viruses play a major role in controlling the structure and dynamics of microbial communities in anaerobic digesters, ecosystems sensitive to disturbances that inhibit methane production. Here, we studied the interplay between abiotic disturbances, microbiome and virome composition, and process performance, to assess whether provirus induction can be triggered by abiotic stresses known to inhibit anaerobic digestion (ammonium, phenol and sodium chloride). We monitored viral dynamics in batch mesophilic anaerobic digesters fed with biowaste through shotgun metavirome sequencing. The diversity of both prokaryotes and viruses was high, with Clostridiales dominating the prokaryotic community and Caudoviricetes dominating the viromes. We identified 132 viral contigs and 19 host genera that were differentially abundant under disturbed conditions. No significant impact of the tested abiotic stresses on provirus induction was observed under the current experimental and analytical framework. The results were consistent with viruses exerting steady, background-level predation through a putative combination of kill-the-winner dynamics at the sub-genus level and piggyback-the-winner dynamics, rather than stress-triggered, synchronous lytic bursts. A few auxiliary metabolic genes were detected, potentially targeting carbon, sulfur and cofactor metabolism in anaerobic digestion. Temperate viruses were dominant, representing up to 71% of the viral genomes confirmed as complete across all conditions. Electron microscopy analysis revealed diverse virus-like particles, including head-tailed particles typical of Caudoviricetes, but also spherical, rod-shaped and spindle-shaped particles typical of archaeal viruses. Notably, we present a new virus family, Eurekaviridae, of spindle-shaped viruses associated with methanogenic archaea.

Anaerobiosis↗
PubMed2026

Building biofilms for saline hydrogenotrophic denitrification from contrasting origins: Convergent acclimation, divergent performance.

Hydrogenotrophic denitrification is promising for deep nitrogen removal from saline, low-C/N wastewaters, but rapid establishment of stable biofilms at high salinity remains challenging. Here, two saline-adapted inocula from two representative, functionally contrasting habitats-a functionally-diversified inoculum from mangrove sediment and a functionally-focused inoculum from seabed sediment-were acclimated in parallel H2-based membrane biofilm reactors at constant 3.5% salinity. The Diverse-derived biofilm required 80 d to reach steady state and achieved only partial denitrification with 61.1% nitrate removal and considerable nitrite accumulation. In contrast, the Focus-derived biofilm rapidly established complete denitrification within ∼40 d, which was maintained for >50 d, with effluent NOx- below 1 mg-N·L-1 and 98.7% nitrate removal. Microbiome analyses showed that identical operation promoted convergence in community structure and enriched similar community-level functional potentials. However, genome-resolved analysis revealed distinct source-dependent functional organization among dominant microbial populations. Complete denitrifiers co-encoding denitrifying, hydrogenotrophic, and autotrophic functions were preferentially enriched in the Focus-derived biofilm, whereas these functions remained partitioned among different dominant populations in the Diverse-derived biofilm, coinciding with less complete denitrification. These findings indicate that saline hydrogenotrophic denitrification performance depends not only on which functions are enriched at the community level, but also on how key functions become organized among microbial populations, providing a previously overlooked criterion for inoculum selection in saline biological nitrogen control.

Complete denitrification↗
PubMed2026

Genetic legacy effects in a mungbean-wheat rotation reveal potential to breed for system-level yield gains.

Legume crops provide protein-rich food, serve as critical disease breaks in cereal rotations, and contribute to soil fertility through symbiotic nitrogen fixation. However, crop improvement programs typically focus on within-crop performance rather than system-level benefits. We hypothesize that legacy effects (the influence of one crop's genotype on subsequent crop performance) are under genetic control and could be targeted in breeding programs. To test this, we evaluated how 309 genetically diverse mungbean genotypes influenced subsequent wheat performance. The mungbean panel was grown, followed by a single wheat cultivar sown in the same plots. Remarkably, wheat yield varied by nearly 1 t ha-1 (2.52-3.49 t ha-1), depending solely on the preceding mungbean genotype. Legacy effects showed moderate heritability (H2: 0.43-0.65), suggesting untapped genetic potential for breeding. However, these estimates were derived from a single site and season and require validation across environments. Analyses of mungbean traits, soil properties, and volatile organic compounds identified root architecture, symbiotic nitrogen fixation, and the soil microbiome as potential contributors to legacy effects, although these mechanisms remain to be tested directly. Haplotype mapping identified genomic regions in mungbean associated with wheat yield and, to a lesser extent, grain protein, revealing trade-offs between within-crop performance and legacy effects. Genetic simulations based on empirically derived marker effects compared genomic selection strategies targeting mungbean yield, wheat yield, or both simultaneously. A selection strategy placing equal weight on mungbean yield and subsequent wheat yield (50:50 weighting) achieved simultaneous gains in both crops (19.5% and 7.6%), highlighting the potential to breed for system-level productivity with reduced input requirements.

crop rotations↗
PubMed2026

Precision Engineering of Evolution-Resilient Rice against Bacterial Blight.

The persistent conflict between rice and Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight, exemplifies a dynamic genetic arms race in agriculture. The cyclical deployment and erosion of major resistance (R) genes highlight the high adaptive potential of Xoo and the need for strategies that are durable rather than absolute. This review synthesizes a paradigm shift from reactive, single R-gene deployment toward proactive engineering of evolution-resilient resistance. We explore the molecular-genetic basis of Xoo adaptability, including TAL effector diversification, non-TAL virulence functions, genome variation, and immune suppression mechanisms. In response, we propose a framework for durable disease management with three connected components: precision disarmament through editing of susceptibility-gene effector-binding elements and executor/decoy designs; smart induction through targeted delivery and immune priming; and ecological fortification through protective microbiomes. We also discuss the limits, trade-offs, and field-validation requirements of these approaches. Integrating frontier technologies with evolutionary genetics, predictive genomics, and pathogen population dynamics can help develop rice varieties and deployment systems that are more difficult for Xoo populations to overcome.

CRISPR↗
PubMed2026

An Acetyltransferase Conferring Self-Resistance of the Producer to Lasso Peptide Antibiotic Lariocidin.

The soil microbiome, a reservoir of antibiotic-producing bacteria, also harbors resistance determinants encoded within antibiotic biosynthetic gene clusters (BGCs). Studying self-resistance mechanisms, which have evolved in producers to protect against their own toxic metabolites, provides critical insights into the evolution of resistance and the potential vulnerabilities of new antibiotics and can facilitate the production of natural products in heterologous hosts. Here, we describe the self-resistance mechanism to lariocidin (LAR), a recently discovered lasso peptide antibiotic that inhibits the ribosomal machinery and exhibits antibacterial activity against key pathogens. We identified and characterized an N-acetyltransferase enzyme (LrcE) encoded within the LAR BGC that mediates self-resistance in LAR-producing Paenibacillus sp. M2. LrcE is a member of the GCN5-related N-acetyltransferase (GNAT) superfamily and performs site-specific acetylation of LAR at a critical lysine residue. This modification disrupts ribosomal binding, thereby reducing LAR's antibacterial activity. Using in silico modeling, we predicted a conserved acetyl-CoA-binding motif and an LAR-binding region on LrcE. Bioinformatic analysis revealed LrcE homologues in environmental but not clinically relevant pathogens, suggesting a limited risk of horizontal gene transfer and, therefore, supporting the further development of LAR as a next-generation antibiotic.

Anti-Bacterial Agents↗
PubMed2026

Human Milk Oligosaccharides Modulate Nitrogen Utilization in Lactobacillus crispatus in a Glucose-Dependent Manner.

The vaginal microbiome's transition to a dysbiotic state increases susceptibility to pathogens like group B Streptococcus. While human milk oligosaccharides are established prebiotics in the neonatal gut, their impact on the vaginal niche remains largely unexplored. This study investigated the effects of pooled human milk oligosaccharides on the growth and physiology of vaginal (Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners) and gut-derived (Lactobacillus reuteri, Lactobacillus rhamnosus) commensals. Growth analyses revealed that human milk oligosaccharides significantly and selectively stimulated growth across all vaginal strains tested, whereas gut commensals exhibited variable or inhibited growth. Carbohydrate utilization assays and comparative genomics against Bifidobacterium infantis showed that Lactobacillus crispatus and Lactobacillus reuteri lack the canonical metabolic machinery to catabolize human milk oligosaccharides. Instead, nitrogen utilization assays identified a glucose-dependent pathway where human milk oligosaccharides are associated with the depletion of primary amines and amino acids in Lactobacillus crispatus supernatants. These results suggest that human milk oligosaccharides act as noncatabolic modulators of vaginal lactobacilli. Collectively, these in vitro findings may warrant investigation of human milk oligosaccharides as modulators of vaginal commensal physiology in more complex experimental systems.

Humans↗