African swine fever (ASF), caused by the highly contagious African swine fever virus (ASFV), poses a significant threat to domestic and wild pigs worldwide. Despite its limited host range and lack of zoonotic potential, ASF has severe socio-economic and environmental consequences. Current control strategies primarily rely on early detection and culling of infected animals, but these measures are insufficient given the rapid spread of the disease. Developing effective therapeutics against ASFV is crucial to prevent further spread and mitigate economic losses. Although vaccination remains critical, recent vaccine approvals in Vietnam have raised safety and efficacy concerns. Moreover, as challenges persist in vaccine development and deployment, particularly in complex field conditions, antiviral agents have emerged as a critical complementary approach. These agents have the potential to mitigate side effects and control viral spread when vaccines alone are insufficient or when animals face simultaneous exposure to vaccine strains and wild-type viruses. However, advancing them from proof-of-concept to widespread practical application entails a significant interdisciplinary effort, given the logistical and economic constraints of in vivo testing. In this review, we examine emerging antiviral approaches and highlight key ASFV replication mechanisms and therapeutic targets to guide rational drug design amidst an evolving viral landscape.

Histone-like nucleoid structuring protein H-NS plays a pivotal role in orchestrating bacterial chromatin and regulating horizontal gene transfer (HGT) elements. In response to environmental signals, H-NS undergoes dynamic post-translational modifications (PTMs) that resemble the epigenetic codes of eukaryotic histones. This review explores how environmental cues regulate PTMs at specific sites within distinct domains of H-NS, thereby modulating its oligomerization and DNA-binding capabilities to reprogram bacterial responses. Notably, HGT elements commonly encode counter-silencing factors, including PTM-modifying enzymes, that counteract H-NS repression. We propose that combinatorial PTM patterns on H-NS form the bacterial histone-like epigenetic code, regulating the expression of HGT elements. Collectively, these interactions establish a sophisticated network of silencing and counter-silencing mechanisms that drive bacterial genome evolution.

Metabolic engineering is a key enabling technology for rewiring cellular metabolism to enhance production of chemicals, biofuels, and materials from renewable resources. However, how to make cells into efficient factories is still challenging due to its robust metabolic networks. To open this door, metabolic engineering has realized great breakthroughs through three waves of technological research and innovations, especially the third wave. To understand the third wave of metabolic engineering better, we discuss its mainstream strategies and examples of its application at five hierarchies, including part, pathway, network, genome, and cell level, and provide insights as to how to rewire cellular metabolism in the context of maximizing product titer, yield, and productivity. Finally, we highlight future perspectives on metabolic engineering for the successful development of cell factories.

Human oncogenic viruses contribute significantly to the global health burden and include seven types: Epstein-Barr virus, hepatitis B virus, human T-cell leukemia virus type 1, human papillomavirus, hepatitis C virus, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus. While the roles of latent or integrated viral genomes in cancer have been documented, emerging evidence highlights the contribution of defective viruses-those carrying intragenic deletions or loss-of-function mutations-in promoting viral oncogenesis. These altered genomes often lack genes essential for lytic replication or immune recognition, which enhances their persistence and immune evasion. In virus-associated diseases, specific patterns of gene retention and deletion suggest that host-driven selective pressures drive the emergence of these altered genomes. This review examines the generation, prevalence, and functional impact of these viruses, reframing them as active participants in disease development and progression. Recognizing their role offers new insights into viral tumor evolution and creates opportunities for applications in viral diagnostics and targeted intervention strategies.

Escherichia coli and Bacillus subtilis provide well-studied models for understanding how bacteria manage DNA replication stress (RS). These bacteria employ various strategies to detect and stabilize stalled replication forks (RFs), circumvent or bypass lesions, resolve replication-transcription conflicts (RTCs), and resume replication. While central features of responses to RS are broadly conserved, distinct mechanisms have evolved to adapt to their complex environments. In this review, we compare the RS sensors, regulators, and molecular players of these two phylogenetically distant bacteria. The differing roles of the RecA recombinase are used as the touchstone of the distinct strategies each bacterium employs to overcome RS, provided that the fork does not collapse. In E. coli, RecA mainly assembles at locations distal from replisomes, promotes global responses, and contributes to circumvent or bypass lesions. RecA assembles less frequently at stalled RFs, and its role in lesion skipping, fork remodeling, RTC resolution, and replication restart remains poorly defined. In contrast, in B. subtilis, RecA assembles at stalled forks, fine-tunes damage signaling, and, in concert with RecA-interacting proteins, may facilitate fork remodeling or lesion bypass, overcome RTCs, and contribute to replication restart.

The genus Enterococcus comprises a diverse group of species, many of which are commensal members of the gut microbiota of humans and animals. The two most prominent species associated with humans, Enterococcus faecalis and Enterococcus faecium, have also emerged as prominent opportunistic pathogens causing a range of infections in hospitalized patients, including urinary tract infections, bloodstream infections, and endocarditis. The rise of antibiotic resistance in enterococci undermines the efficacy of the treatment of infections, thus posing a significant public health risk. Enterococci readily acquire resistance to antibiotics through chromosomal mutations and the horizontal gene transfer of antibiotic resistance genes. This review offers a comprehensive examination of the mechanisms of antibiotic resistance among enterococci, with an emphasis on resistance to last-line antibiotics, including to glycopeptide antibiotics like vancomycin and teicoplanin, oxazolidinones (primarily linezolid), and daptomycin. Furthermore, we evaluate relevant candidates in the current development pipeline for antibiotics and discuss alternative strategies (phage therapy and immunotherapeutics) for the treatment and prevention of infections with multidrug-resistant enterococci. As enterococci rapidly adapt to novel conditions, including by developing resistance to new drugs and therapies, sustained research efforts are required to ensure the continuous development of treatment options for these important opportunistic pathogens.

Coenzyme A (CoA) biosynthesis is a crucial process in living organisms, characterized by the production of conserved intermediates through enzyme-catalysed steps that vary across species. The synthesis of CoA entails several conversions, starting from pantothenate. Pantothenate is an essential vitamin in humans and is synthesized by certain bacterial species. Intermediates of the biosynthetic pathway have been shown to impact bacteria, especially in community settings such as the intestinal microbiota. Additionally, various diseases have been associated with specific CoA precursors and metabolic pathways downstream of CoA in the gut microbiota, underscoring the significance of evaluating the current knowledge on how the CoA pathway influences the metabolic state of bacteria. This also highlights the importance of having standardized methodologies that can be employed to better understand the metabolism of the microbiome. In this review, we explore the current literature on bacterial CoA metabolism, with a particular focus on gut bacteria and the impact of CoA-related metabolites on bacterial composition, function and metabolism. Furthermore, we discuss previous and current methodologies employed to investigate CoA biosynthesis. Our goal is to provide valuable insights into the intricate relationship between CoA metabolism, gut microbiota and their implications for health and disease, offering a foundation for future research and therapeutic approaches.

The Bacterial Locomotion And Signal Transduction (BLAST) conference was founded in 1991 and has been held biennially thereafter. While BLAST meetings have typically covered two-component and chemotactic signaling, as well as aspects of motor and flagellum, this year's program broadened its scope and included emerging areas of research, such as microbial signal perception, cellular signal processing, downstream physiological impacts of bacterial signaling, microbe interactions and communities, integrative approaches, and technology innovations. This review summarizes the oral presentations from BLAST XVIII, held in January 2025 in Cancun, Mexico.

Microbial manufacturing offers a sustainable and environmentally friendly approach for chemical production. However, the inherent toxicity of certain high-value chemicals to microbial cell factories presents a significant challenge, severely constraining production efficiency. To enhance microbial tolerance, extensive synthetic biology strategies have been developed. The cell envelope serves as the primary natural barrier in microorganisms, and both its intrinsic composition, including membrane lipids, membrane proteins, and cell wall components, and the regulation of these components play crucial roles in modulating cellular responses to environmental stress. Engineering strategies targeting intracellular components, such as transcription factors and repair pathways, have demonstrated effectiveness in enhancing microbial tolerance to toxic end-products and intermediates. Additionally, recent advances have focused on extracellular engineering, including biofilm formation and the modulation of intercellular interactions, which have garnered significant scientific interest. This review aims to provide a systematic overview of these strategies and offers insights to facilitate the industrial translation and commercialization of microbial production of toxic end-products and intermediates.

Staphylococcus aureus, a leading human pathogen, is increasingly recognized as a genotoxic bacterium that reshapes host cell integrity beyond its classical virulence traits. By inducing DNA damage in host cells, S. aureus activates host DNA damage response (DDR) pathways that can determine the balance between bacterial clearance and persistence. By promoting chromatin remodeling and epigenetic reprogramming, through bacterial effectors such as phenol-soluble modulins and infection-induced metabolic changes, S. aureus modulates host immune responses and supports intracellular persistence. These interconnected mechanisms link DNA damage with immune evasion, chronic inflammation, and long-term tissue remodeling, which may contribute to carcinogenesis in chronically infected tissues. Recognizing S. aureus as both an infectious and genotoxic agent opens new therapeutic perspectives. Targeting DDR and epigenetic pathways, or modulating trained immunity to restore protective responses, offers promising strategies to counteract bacterial persistence and limit infection-associated pathologies. This integrative perspective redefines the pathogenesis of S. aureus by linking its genotoxic activity to host cellular reprogramming, and underscores the potential of host-directed therapeutic strategies as complementary approaches to conventional antibiotic treatment. It establishes a conceptual framework for understanding S. aureus persistence and pathogenicity in the context of rising antibiotic resistance.

In the innovative field of engineered living materials (ELMs) microbiology and material sciences meet. These materials incorporate living organisms, such as bacteria, fungi, plants, or algae, to enable unique functions like self-assembly, actuation, and dynamic interaction. By utilizing (micro)biological systems in material design, ELMs promise to transform industries including healthcare, construction, and agriculture. In the early phase of ELM technology development, researchers implemented a single living strain in an already established user material. However, the complexity and potential of these materials is limited by the abilities of this single strain. Even though synthetic biology brings the opportunity to add a range of nonnative bioactivities to these cells and thus the material, the increasing metabolic burden upon implementation of multiple nonnative pathways limits the capacity of a single strain. Furthermore, higher organisms and nonstandard hosts are often desired in material settings for their native physical or metabolic advantages. However these are not always straightforward to further engineer. Thus, the use of multiple, specialized strains broadens the functionalities and thus the applicability of ELMs. Multistrain ELMs are a brand-new technology, with many promising applications.

Leptospirosis is one of the most common zoonotic infections in the world and is considered a neglected disease. Development of molecular methods and approaches in gene typing significantly contributed to the discovery of novel Leptospira strains, which require detailed studying and systematization and are an important factor of managing the pathogen and the disease leptospirosis as a classic One Health problem. Characterization of Leptospira populations in water, soil, and other environmental objects will aid in the development and implementation of prevention and control approaches aimed at reducing the risks of infection, and will contribute to a deeper understanding of the bacteria's ecology. This study aimed to briefly describe the phylogenic history of Leptospira spp., and to conduct a review and retrospective analysis of new strains discovered during the years 2000-2025 impacting the leptospires landscape significantly. The discovery of novel Leptospira strains has been an important development in the research of this pathogen, and has helped to better understand the potential risks associated with its presence. In this review, we analyzed and summarized literature on the detection of new Leptospira strains and their global distribution.

One hundred years after planctomycetes were discovered and 50 years since the first isolate was successfully cultured, this bacterial phylum remains enigmatic in many ways. In the last few decades, a significant effort to characterize new isolates has resulted in >150 described species, allowing a more comprehensive analysis of their features. However, metagenomic studies reveal that a diverse group of planctomycetes has yet to be cultured and characterized, and that many biological surprises are yet to be revealed. This is the case for the recently discovered phagotrophic Candidatus Uabimicrobium, which challenges our understanding of the distinction between prokaryotes and eukaryotes. The unique biology of planctomycete cells, such as their ability to divide without the FtsZ protein, their complex structure and characteristic morphology, their relatively large genomes containing many genes with unknown function, and their variable metabolic capabilities, imposes significant barriers for researchers. Although ubiquitous, the precise ecological roles of planctomycetes in various environments are still not fully understood. However, their distinctive metabolism opens the door to a large number of potential biotechnological applications, which are beginning to be unveiled. In this article, we first review the historical milestones in planctomycetes research and describe the pioneers of the field. We then describe the controversies and their resolutions, we highlight the past discoveries and current interrogations related to planctomycetes, and discuss the ongoing challenges that hinder a comprehensive understanding of their biology. We end up with directions for exploring the biology and ecological roles of these fascinating organisms.

Mtb subverts host immune surveillance by damaging phagolysosomal membranes, exploiting them as replication niches. In response, host cells initiate a coordinated LDR, integrating membrane repair, selective autophagy, and de novo biogenesis. This review delineates a systems-level model of lysosomal quality control governed by three critical regulatory axes: LGALS3/8/9, TRIM E3 ubiquitin ligases, and the AMPK-TFEB signaling pathway. LGALSs detect exposed glycans on ruptured membranes, triggering ESCRT-mediated repair and recruiting ARs. TRIM proteins mediate context-specific ubiquitination, enhancing cargo selection and facilitating transcriptional reprogramming via TFEB. Simultaneously, AMPK-TFEB signaling links metabolic stress to lysosomal regeneration, reinforcing immune defense and cellular adaptation. We highlight emerging mechanisms, including ATG8ylation, CASM, Ca2 + leakage, and SG formation, that refine this multilayered response. Mtb virulence factors selectively disrupt these pathways, revealing their relevance to pathogen persistence. Beyond infection, this triadic network maintains lysosomal integrity in neurodegeneration, inflammation, and lysosomal storage disorders. Understanding its modular design reveals novel therapeutic targets and HDTs for combatting drug-resistant TB. This review integrates recent advances into a coherent framework that redefines lysosomal function as a dynamic, immune-regulatory hub essential for cellular resilience under infectious and metabolic stress.

Biodegradation plays a pivotal role in controlling environmental pollution. Naturally occurring microbes can degrade various environmental pollutants; however, the bioremediation of emerging pollutants resulting from the synthesis of recalcitrant organic compounds has not been sufficiently studied. These compounds pose significant environmental risks when released into soil and water bodies. Therefore, it is essential to accelerate the acquisition of knowledge on their biodegradation and foster the development of advanced bioremediation strategies. Recent progress in sequencing technologies and high-precision analytical instruments, coupled with ever-increasing computing power, has revolutionized conventional biodegradation research. In this review, the fundamental principles and commonly used techniques in bacteria-mediated biodegradation were discussed, emphasizing an integrated approach for a comprehensive understanding of the biodegradation process. This review provides in-depth insights into the current progress and prospects of biodegradation research.

Targeted degradation is emerging as a new therapeutic approach in the treatment of different diseases. It allows hijacking the cellular pathways deputed to protein or nucleic acid homeostasis to degrade a target macromolecule of interest involved in a pathogenic process. In the last decades, targeted protein degradation has been widely applied for the treatment of cancer or neurodegenerative disorders and some of such therapies are already in clinical use. More recently, therapeutic degraders such as PROTACs, LYTACs, HyTs, BacPROTACs, and others have also been explored in the field of antimicrobial and antiviral drug discovery. The peculiar mechanism of action, along with the opportunity to degrade both microbial and host targets, holds great promise for overcoming some limitations of classic antimicrobials, e.g. drug resistance, as well as for increasing the potency of current therapies. With a focus on the antimicrobial field, this Review aims at providing a comprehensive, state-of-the-art description of targeted degradation mechanisms and strategies developed so far, as well as to discuss advantages, disadvantages, and caveats of this innovative approach for combating infectious diseases.

Bacterial vaginosis (BV) is a complex polymicrobial vaginal infection that affects a large percentage of women during different stages of life including the reproductive age. In a healthy vaginal environment, the epithelium is colonized by protective Lactobacillus species that make up 90%-95% of the total vaginal microbiota. BV is characterized by a reduction of lactobacilli and a concurrent increase in diverse anaerobic bacteria, including Gardnerella vaginalis, Prevotella bivia, Hoylesella timonensis, and Fannyhessea vaginae. BV is associated with an increased risk of infertility, preterm birth, and a higher susceptibility to sexually transmitted infections (STIs), including Human Immunodeficiency Virus type-1 (HIV-1). This review examines the contribution of individual pathogenic bacteria to the development of BV and the resulting effects on susceptibility to STI. The impact of the different key bacterial virulence factors, such as secreted proteins, biofilm formation, and inflammatory potential on subsequent viral infection are discussed. While antibiotics are commonly prescribed to treat BV, recurrence rates are high, and antimicrobial resistance among BV-associated bacteria is increasingly reported. Understanding the mechanisms underlying BV and the impact of specific bacteria and their virulence factors on viral infections can improve preventive strategies and open up novel therapeutic applications.

Glycolysis stops where gluconeogenesis starts-at pyruvate, the central metabolite of biosynthesis. The early history of carbon metabolism is preserved in archaeal and bacterial enzymes for glucose synthesis and breakdown. Here, we summarize the distribution and phylogeny of enzymes involved in glycolysis, gluconeogenesis, and glycogen metabolism from genomes of cultured prokaryotes. The presence of glycolytic pathways in H2-dependent chemolithoautotrophs, including methanogens, which cannot grow on exogenous glucose, correlates with their use of glycogen for intracellular carbon storage. Glycogen synthesis and gluconeogenesis are universal among prokaryotes, but glycolysis is not, indicating that the enzymatic conversions of glycolysis arose in the gluconeogenic direction encompassing three phases: (1) an autotrophic origin from H2 and CO2 to pyruvate and triosephosphate (trunk glycolysis) fulfilling basic amino acid and cofactor synthesis in the last universal common ancestor, (2) from triosephosphate to glucose supplying cell wall (murein and pseudomurein) and nucleic acid biosynthetic requirements in the first free-living autotrophs, also giving rise to intracellular carbon reserves (glycogen), followed by (3) diversification and transfer of enzymes for glycogen-mobilizing glycolytic routes. An autotrophic origin of trunk glycolysis followed by glycogen-dependent origin of glucose utilization account for conservation, distribution, and diversity of enzymes observed in microbial sugar phosphate pathways.

Host-mediated natural competence for transformation of DNA and mobile genetic element (MGE)-driven conjugation and transduction are key modes of horizontal gene transfer. While these mechanisms are traditionally believed to shape bacterial evolution by enabling the acquisition of new genetic traits, numerous studies have elucidated an antagonistic relationship between natural transformation and MGEs. A new role of natural transformation as a chromosome-curing mechanism has now been proposed. Experimental data, along with mathematical models, suggest that transformation can eliminate deleterious MGEs. Supporting this hypothesis, MGEs have been shown to use various mechanisms to decrease or block transformability, such as disrupting competence genes, regulating the development of competence, hindering DNA uptake machinery, producing DNases that target the exogenous (transforming) DNA, and causing lysis of competent cells. A few examples of synergistic relationships between natural transformation and MGEs have also been reported, with natural transformation facilitating MGE transfer and phages enhancing transformation by supplying extracellular DNA through lysis and promoting competence via kin discrimination. Given the complexity of the relationships between natural transformation and MGEs, the balance between antagonism and synergy likely depends on specific selection pressures in a given context. The evidence collected here indicates a continuous conflict over horizontal gene transfer in bacteria, with semiautonomous MGEs attempting to disrupt host-controlled DNA acquisition, while host competence mechanisms work to resist MGE interference.

Group A Streptococcus (GAS) has recently reemerged as a leading cause of both mild and severe invasive infections worldwide, with recent upsurges in invasive disease among children and adults. Notwithstanding a partial synchronicity with the COVID-19 pandemic, this rapid global dissemination of more virulent GAS lineages has been promptly detected, as well as the molecular shifts underlying the observed changes in clinical patterns. Whole-genome sequencing (WGS)-based genomic epidemiology allowed us to gain relevant insights into this upsurge as it was happening. This review integrates the canonical research publication-based approach with genomic data and metadata and identifies a subset of genomic clusters playing a major role in invasive GAS (iGAS) infections worldwide, which were named as Global Pathogenic Lineages (GPLs). The four GPLs broadly coincide with five sequence types (STs): GPL1 with ST28, GPL2 with ST15 and ST315, GPL3 with ST52, and GPL4 with ST39. While non-GPLs clusters maintain a baseline reservoir of antimicrobial-resistance and virulence genes, GPLs show varying but noteworthy resistance profiles and are frequent causes of iGAS. The integration of WGS into routine diagnostics procedures is a forthcoming improvement, aimed not only at informing tailored therapy and implementing infection control strategies, but also to perform continuous surveillance. Ongoing WGS in clinical microbiology, as a matter of fact, will provide unparalleled insights into lineage emergence, transmission dynamics, and the geographic clustering of virulence and resistance determinants.