mSystems最新文献

The marine dissolved organic matter (DOM) pool is one of Earth's largest carbon reservoirs and a critical regulator of global carbon flux, yet the microbe-molecule interactions governing it remain largely unresolved. In a significant advancement, McParland and colleagues integrate a 3-year, depth-resolved molecular time series of DOM with parallel taxonomic characterization of prokaryoplankton at the Bermuda Atlantic Time-series Study site to examine the coupling between community composition and DOM molecules (E. L. McParland, F. Wittmers, L. M. Bolaños, C. A. Carlson, et al., mSystems 11:e01540-25, 2026, https://doi.org/10.1128/msystems.01540-25). Their analysis reveals high temporal coordination, with approximately 40% of both DOM molecules and microbial taxa exhibiting 12-month periodicities. However, interannual patterns in DOM composition appear more predictable than that of microbial communities, suggesting that functional redundancy, conferred through core metabolic pathways shared across taxa, may act as a stabilizing force for ocean chemistry. By highlighting the endurance of these functional roles, McParland and colleagues provide a framework for incorporating microbial processes into more mechanistic and predictable biogeochemical models.

Bloodstream infections caused by Staphylococcus aureus remain a leading cause of mortality worldwide. Our understanding of S. aureus survival and persistence in human serum, a cell-free fraction of blood hostile for bacteria, is still limited. Here, we applied multivariate data integration methods and network analysis to a multi-omic data set generated from five clinically prevalent S. aureus genotypes exposed to human serum. We observed, and then confirmed using isogenic mutants the significant roles of gapdhB, sucA, sirA, sstD, and perR in bacterial survival in serum. These data show that metabolic versatility in carbon source usage, iron transport, and resistance to oxidative stress is interlinked and central to S. aureus fitness in serum, representing potential S. aureus vulnerabilities that could be exploited therapeutically.IMPORTANCEBloodstream infections caused by Staphylococcus aureus are associated with mortality rates of up to 30%. However, the molecular mechanisms that enable this pathogen to survive in human serum-a nutrient-limited and immunologically hostile environment-remain poorly understood. By integrating multi-omic data from five clinically relevant S. aureus genotypes and validating key signatures using mutants, we identified conserved genetic determinants critical for bacterial survival in serum. Our findings highlight the interconnected roles of carbohydrate metabolic flexibility, iron acquisition, and oxidative stress resistance in shaping S. aureus adaptation to serum. This work advances our understanding of microbial strategies to survive in the bloodstream and demonstrates the potential of multi-omic integration to uncover therapeutic vulnerabilities in bacterial pathogens.

Staphylococcus aureus is a major source of community and nosocomial infections. Due to the extensive application of antibiotics, S. aureus has developed resistance to antibiotics, especially vancomycin, making clinical treatment challenging. Staphylococcal accessory regulator A (SarA) modulates S. aureus virulence by regulating the principal virulence factors. However, its role in vancomycin resistance remains largely unknown. Herein, we found that SarA not only reduces the susceptibility of S. aureus to vancomycin by directly inhibiting the expression of autolysis-related genes, but also enhances resistance to vancomycin by negatively regulating the transcription of an ATP-binding cassette (ABC) transporter, ABC-like, thereby altering the bacterial surface charge and reducing vancomycin's binding efficiency to the cell wall. Moreover, the regulation of antibiotic resistance by SarA is strain-dependent. Our study uncovers the roles of SarA in regulating vancomycin resistance, providing potential targets and ideas for the prevention and control of vancomycin-intermediate S. aureus infections.IMPORTANCEStaphylococcus aureus poses a major threat to public health due to its increasing resistance to vancomycin, a last-line antibiotic. This study reveals that Staphylococcal accessory regulator A regulates vancomycin resistance in S. aureus by suppressing genes related to autolysis and negatively regulating an ATP-binding cassette (ABC) transporter (ABC-like). This regulation of the transporter reduces the bacterial surface charge, impairing the ability of vancomycin to bind to the cell wall. These findings suggest a novel mechanism of antibiotic resistance in S. aureus and identify potential targets for combating vancomycin-intermediate S. aureus infections.

Understanding how different microbial groups respond to broad environmental gradients is essential for revealing the processes that structure microbial diversity. In this study, we comparatively investigate the ecological drivers that shape β-diversity across different microbial domains/kingdoms (bacteria, archaea, fungi, and protists) in intertidal mudflats along a broad climatic gradient, spanning ~18,000 km along the Chinese coastline. Distinct latitudinal β-diversity patterns are observed for different microbial domains/kingdoms. Null model analyses reveal significant deviations in β-diversity from null expectations across all microbial domains, with bacterial and archaeal β-diversity primarily associated with the γ-diversity or regional species pools, whereas fungal and protist communities were more strongly shaped by local community assembly processes. Homogeneous selection is the predominant assembly process, with varied relative influence of environmental variables across different domains/kingdoms as revealed by db-RDA. These findings underscore the importance of domain-specific ecological processes in shaping microbial biogeography and highlight the need for comparative frameworks across microbial groups to understand biodiversity patterns along environmental gradients.IMPORTANCEUnderstanding the spatial distribution of biodiversity is a fundamental goal in ecology, yet most microbial studies focus on single domains. This study provides a comprehensive comparison of bacteria, archaea, fungi, and protists along an ~18,000 km latitudinal gradient in intertidal mudflats. We reveal that these microbial domains do not follow a unified diversity pattern but are instead governed by distinct ecological drivers. Bacteria and archaea are strongly influenced by regional species pools, whereas fungal and protist communities are primarily shaped by local stochastic processes such as dispersal limitation. These findings highlight the importance of organismal traits (e.g., body size) in shaping community assembly. This work emphasizes the necessity of establishing a multi-domain framework to accurately predict how Earth's complex microbiomes respond to environmental changes.

Sinks contaminated with opportunistic pathogens are a source of hospital-acquired infections, responsible for morbidity and mortality in neonatal intensive care units (NICUs). Understanding pathogen behavior in sinks is essential for preventing their spread. Only a few studies have examined how sink environments affect pathogen distribution through changes in drain microbiota. This research uses an integrative approach to study three major bacterial pathogens: Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Serratia marcescens. Sink drains in two NICUs were sampled during 2-month and 5-month periods. The diversity and abundance of opportunistic pathogens were determined at the genotypic level. Their occurrence was analyzed considering microbial communities, water parameters, faucet design, and sink usage. P. aeruginosa, S. marcescens, and S. maltophilia were found in 47%, 39%, and 67% of drain samples, respectively. Low genotype diversity was observed within sinks, with 1-3 genotypes per species/sample. Dominant genotypes persisted throughout the sampling periods, showing the persistence of opportunistic pathogen strains in drains. Quantification of the studied bacterial sequence types ranged from 10³ to 10⁷ DNA copies/mL. The heterogeneous spatial distribution of the three species between individual sink drains was primarily attributed to changes in community composition, chlorine concentrations, and faucet design. We isolated a strain of Delftia tsuruhatensis (Dt1S33), whose presence in the sink environment was negatively correlated with the three opportunistic pathogens. Dt1S33 reduced the capacity of the pathogens to form biofilms in laboratory co-cultures. These findings underscore the key roles of biotic and abiotic factors in the colonization of sink drains by pathogens.IMPORTANCEHospital sinks are critical reservoirs for opportunistic pathogens (OPs), increasing the risk of healthcare-associated infections, especially in vulnerable populations such as neonatal intensive care unit (NICU) patients. Our study found that 39%-67% of sink drains were persistently colonized by Pseudomonas aeruginosa, Serratia marcescens, and Stenotrophomonas maltophilia, with a limited number of genotypes dominating for months. Colonization patterns in drains varied between NICUs, mainly influenced by microbial community composition and sink design. Notably, Delftia tsuruhatensis presence was negatively correlated with OP colonization and inhibited OP biofilm formation in vitro. These results highlight the interplay of abiotic and biotic factors in sink colonization and suggest that antagonistic bacteria could help reduce pathogen persistence. Understanding these dynamics is crucial for developing targeted interventions to mitigate infection risks in high-risk hospital settings.

The human gut microbiome is a dynamic ecosystem. Host behaviors (e.g., diet) provide a regular source of environmental variation that induces fluctuations in the abundances of resident microbiota. Despite these displacements, microbial community members remain highly resilient. Population abundances tend to fluctuate around a characteristic steady-state over long timescales in healthy human hosts. These temporary excursions from steady-state abundances, known as sojourn trajectories, have the potential to inform our understanding of the fundamental dynamics of the microbiome. However, to our knowledge, the macroecology of sojourn trajectories has yet to be systematically characterized. In this study, we leverage theoretical tools from the study of random walks to characterize the duration of sojourn trajectories, their shape, and the degree that diverse community members exhibit similar qualitative and quantitative dynamics. We apply the stochastic logistic model as a theoretical lens for interpreting our empirical observations. We find that the typical timescale of a sojourn trajectory does not depend on the mean abundance of a community member (i.e., carrying capacity), although it is strongly related to its coefficient of variation (i.e., environmental noise). This work provides fundamental insight into the dynamics, timescales, and fluctuations exhibited by diverse microbial communities.IMPORTANCEMicroorganisms in the human gut often fluctuate around a characteristic abundance in healthy hosts over extended periods of time. These typical abundances can be viewed as steady states, meaning that fluctuating abundances do not continue towards extinction or dominance but rather return to a specific value over a typical timescale. Here, we empirically characterize the (i) length (i.e., number of days), (ii) relationship between length and height, and (iii) typical deviation of a sojourn trajectory. These three patterns can be explained and unified through an established minimal model of ecological dynamics, the stochastic logistic model of growth.

Acute pancreatitis (AP) is a frequent inflammatory disorder with outcomes ranging from mild disease to severe forms marked by infection and organ failure. Gut microenvironment disruption and barrier dysfunction are increasingly recognized as key drivers of AP progression, yet most microbiome studies have focused on bacteria. The gut virome modulates bacterial ecology and host immune responses and remains poorly characterized in AP. We aimed to comprehensively profile virome alterations in AP and evaluate their associations with disease severity, etiology, and clinical parameters. Metagenomic sequencing data from AP patients and healthy controls (HCs) were analyzed using the viromic tools. Viral diversity, taxonomy, functional composition, and predicted viral-host linkages were profiled. Microbial-viral-metabolite networks were constructed, and classification performance was evaluated using random forest models. AP viromes exhibited significantly reduced Shannon and Simpson diversity and distinct β-diversity separation from HCs. AP-enriched phages predominantly targeted Parabacteroides, Escherichia, and Bacteroides, while HC-enriched phages were linked to SCFA-producing commensals. Functional analysis revealed enrichment of replication- and lysis-related auxiliary metabolic genes (AMGs) in AP-enriched viral operational taxonomic units (vOTUs), whereas HC-associated vOTUs carried stability-related functions. Severity- and etiology-stratified analyses indicated consistent enrichment of Peduoviridae infecting Enterobacteriaceae and higher prevalence of eukaryotic viruses in advanced stages. Network analyses revealed denser microbial-viral-metabolite interactions in AP, correlated with hepatobiliary and lipid metabolic markers. A minimal seven-virus panel achieved an AUC of 97.5% for AP classification. AP is characterized by profound gut virome remodeling reflecting disease severity and etiology, with diagnostic and mechanistic relevance for future therapeutic strategies.IMPORTANCEThis study highlights the gut virome as a previously underappreciated component of acute pancreatitis (AP)-associated dysbiosis and suggests that viral communities may influence disease severity and metabolic disturbances beyond bacterial effects alone. By demonstrating the diagnostic potential of virome-based signatures, our findings support expanding microbiome research in AP to include viral components, with implications for improved disease stratification and future therapeutic development.

The inherent barriers posed by bacterial outer membranes, efflux pumps, and biofilm matrices significantly limit the clinical efficacy of antimicrobial agents, underscoring the urgent need for strategies to enhance drug penetration. Integrating pathogen-specific exogenous nutrients with conventional antibiotics has emerged as a promising approach, facilitating the targeted delivery and enhanced efficacy of antimicrobial compounds. In this study, we aimed to improve antimicrobial efficacy by enhancing transmembrane transport. First, we comprehensively compared various genome-scale metabolic reconstruction methods to identify the optimal approach. Subsequently, we enhanced our previous approach to identify exogenous nutrients by integrating topological screening, flux scoring, and chemical structure analysis. Key exogenous nutrients were identified for three pathogens: urea for Acinetobacter baumannii, acetamide for Pseudomonas aeruginosa, and succinic acid for Salmonella enterica. Growth assays confirmed that these nutrients significantly promoted bacterial proliferation. Leveraging these findings, four novel antimicrobial compounds (NC, NA, MA, and MN) were synthesized by conjugating membrane-resistant nalidixic acid or magnolol with the respective nutrients. MN enhanced the antimicrobial activity against wild-type S. enterica by 56.5%, while MA and NA boosted the activity against wild-type P. aeruginosa by 51.4% and 70.4%, respectively. Moreover, NC improved efficacy against drug-resistant A. baumannii by fourfold. These results demonstrate that conjugating exogenous nutrients with antibiotics can effectively enhance antimicrobial activity and help overcome membrane-associated resistance. This nutrient-conjugation strategy offers a promising avenue for developing new antimicrobial agents.IMPORTANCEThe difficulty of achieving effective drug penetration into bacterial cells is a major obstacle limiting antimicrobial efficacy and posing a significant global health challenge. This study demonstrates a novel strategy to combat resistance by "hijacking" nutrients that pathogens rely on for growth. By combining antibiotics with these nutrients, drugs can bypass membrane barriers and effectively reach their targets. The preferred exogenous nutrients of the high-priority pathogens Acinetobacter baumannii, Pseudomonas aeruginosa, and Salmonella enterica were identified. Combining these with the existing antibiotics markedly enhanced antimicrobial efficacy against both susceptible and resistant strains. This approach offers a practical way to revitalize existing antibiotics and design new ones, potentially slowing the spread of resistance. Importantly, it highlights how understanding bacterial metabolism can lead to smarter drug design, addressing a critical need in global health.

Introns are generally considered rare in bacteria, yet they are frequently observed in Patescibacteria, which have highly reduced genomes. To systematically explore the diversity, roles, and evolution of introns in Patescibacteria, we first focused on the tRNA introns. Using 95 complete genomes, we identified tRNA^Asn and tRNA^Asp genes previously undetected by standard annotation tools due to group I introns inserted at an unusual position, 35/36, in the anticodon loop. In vitro splicing assays confirmed that these introns catalyze precise self-splicing, validating our computational approach. A large-scale survey of complete bacterial genomes revealed that intron insertions at position 35/36 are highly enriched in Patescibacteria but rare in other phyla. Subgroup classification indicated that 81% of all tRNA introns belong to the IC subgroup, whereas nearly all Patescibacteria introns were classified as IA. As most tRNA introns lack homing endonuclease genes, horizontal transfer appears limited. Comparative analysis across bacterial phyla showed that Patescibacteria and Cyanobacteriota exhibit the highest prevalence of group I introns (~40% of genomes). In contrast, group II introns, which require protein cofactors for activity, were more common in other bacteria, including Cyanobacteriota, but absent in Patescibacteria. Collectively, these findings suggest that Patescibacteria harbor introns with phylum-specific trends in abundance, structure, and evolutionary lineage. The coexistence of extensive genome reduction and persistent group I introns may reflect an adaptive strategy, where introns serve as efficient RNA-based regulatory elements, potentially substituting for complex protein-mediated systems.IMPORTANCEIntrons were traditionally thought to be rare in bacteria, yet their occurrence and diversity may have been underestimated. Here, we present the first comprehensive overview of group I and group II introns in Patescibacteria. While most introns are readily identified, group I introns inserted at position 35/36 within the anticodon loop often escape detection by standard annotation tools; through experimental verification, we demonstrate that these introns are accurately spliced despite their unusual insertion site. Notably, approximately 40% of genomes in both Patescibacteria and Cyanobacteriota harbor group I introns; however, while around 20% of Cyanobacteriota genomes also contain group II introns, none were detected in Patescibacteria. These results illustrate a previously overlooked phylogenetic distribution of group I and group II introns across the bacterial domain.