Trends in Microbiology最新文献

Antibiotics at sub-minimal inhibitory concentrations (sub-MICs), which are commonly present in food and the environment, can reach the human gut microbiome and silently disrupt the balance of microbes, contributing to the emergence and persistence of antimicrobial resistance (AMR). The gastrointestinal (GI) tract presents spatially heterogeneous antibiotic exposures, making it challenging to assess their full impact with conventional experimental approaches. Although in vitro and in vivo models provide some insight, they often lack physiological relevance or scalability. This highlights the need to reconsider the criteria used to determine 'safe' upper concentration limits in food, as current standards may underestimate the risks of sub-MIC exposures. Therefore, better integrative modeling approaches are essential to uncover hidden drivers of resistance and guide effective interventions.

Next-generation sequencing and bioinformatics paved the way in deciphering the human gut microbiome and challenged fundamental postulates on the causal role of the microbiota for health and pathogenesis of infectious and noncommunicable diseases. To exploit the clinical relevance and potential of microbiome diagnostics and therapy, deep metagenomic sequencing with standardized, validated laboratory procedures, aiming at deciphering the microbiome at strain level and applying index-scores to allow classification of individual microbiomes as dysbiotic (associated with disease) or eubiotic (associated with health) should be implemented. By this means, metagenomically informed therapies with live biotherapeutic products, fecal microbiota transfer, pro-, pre-, or postbiotics might become a standard in personalized prevention and treatment of infectious and non-communicable diseases.

Pathogens can exploit the plasticity of host immune cells, such as the pathway of monocyte differentiation into macrophages and dendritic cells. This review discusses how microbial pathogens hijack the monocyte fate and reprogram macrophages to establish infection, evade immune surveillance, and persist within the host. Viruses such as HIV and cytomegalovirus (CMV) rewire host sentinel cells through modulation of transcriptional networks, cytokine signaling cascades, and autophagic pathways. Bacterial pathogens such as Mycobacterium tuberculosis, Salmonella enterica, or Bordetella pertussis create safe replication niches by disrupting monocyte differentiation. Fungal pathogens expand this repertoire by leveraging cytokine modulation and phenotypic reprogramming to subvert host innate and pathogen-specific immune responses. We highlight here the newly emerging molecular mechanisms of monocyte reprogramming towards pathogen survival and transmission.

The human microbiome plays a crucial role in maintaining homeostasis and influencing disease development, yet its composition varies across geography, age, and lifestyle. These differences challenge the efficacy of universal probiotic treatments and call for more personalized or regionally adapted approaches. In this review we examine the limitations of universal probiotics, emphasizing the importance of considering host-microbe co-adaptation, local dietary practices, and ecological context. We argue that probiotic design must account for microbial diversity, strain-level adaptation, and functional redundancy, and we explore how these factors affect colonization success and therapeutic potential. Finally, we discuss ways to re-center microbiome knowledge within diverse ecological, cultural, and epistemic traditions for a global, inclusive approach allowing for microbiome-targeted therapies that are both effective and accessible.

Nucleocytoplasmic large DNA viruses (NCLDVs) encode multi-subunit RNA polymerases (msRNAPs) that challenge conventional views of viral evolution. Phylogenetic and structural studies reveal that NCLDV RNAP catalytic cores share deep evolutionary roots with eukaryotic counterparts, implicating ancient gene transfers that shaped the last eukaryotic common ancestor (LECA), underscoring NCLDVs' pivotal role in eukaryotic origins. NCLDV RNAP retains the fundamental architecture of cellular RNAPs while evolving and adapting for viral gene regulation. This review summarizes structural and functional divergences between viral and cellular RNAPs, synthesizes evidence for virus-driven RNAP evolution, and evaluates emerging hypotheses of viral eukaryogenesis. Viewing viruses as evolutionary collaborators offers new insights into RNAP adaptability and bridges virology, evolutionary biology, and synthetic biology across diverse biological contexts.

Fundamental research has elucidated the indispensable role of gut microbiota in modulating cancer immunotherapy efficacy. Despite promising preclinical findings, few related approaches have reached clinical trials. In this opinion, we provide insights based on current clinical trials using fecal microbiota transplant or specific bacterial strains as adjuvants to enhance immune checkpoint blockade therapy. We also systematically analyze the challenges in trial design, with a focus on donor selection, patient enrollment, implantation procedures, antibiotic use, safety assessment, and endpoint evaluation. Moving forward, we offer a comprehensive '4D' framework (diversity, diffusion, depth, and delicacy) for accelerating the bench-to-bedside translation. It is hoped that this opinion will help researchers and clinicians aiming to harness microbiome-based strategies to improve cancer immunotherapy outcomes.

Antibiotic combination therapy has a critical role in limiting emergent antibiotic resistance in bacterial pathogens. Collateral sensitivity (CS), resistance to one antibiotic that is inextricable from sensitivity to another antibiotic, presents an opportunity for combinations explicitly selecting against resistance. Complementing efforts to select against resistance, differential genetic vulnerability mapping unravels dependencies unique for resistant strains. In this review, we discuss the potential implications of CS and genetic vulnerability data for the design of bespoke antibiotic combinations, drug discovery, and tracking evolution of resistant strains.

Viral infections of marine microbes greatly impact ecological and biogeochemical processes. Typically, these host-virus interactions are studied at the population level using bulk transcriptomics, which presents a population-averaged perspective and masks diverse infection states. Recent advancements in single-cell technologies enable a simultaneous view of the virus and its host within a population and expose phenotypic heterogeneity during infection. We present a promising avenue for investigating marine viral ecology from a new single-cell perspective to reveal the viral life cycle and host antiviral strategies employed by rare resistant cells. Consequently, we can detect specific host-virus dynamics in the complex natural population, track the spread of infection across ecosystems, and study the ecological impact of marine viruses at an unprecedented resolution.