FEMS microbiology reviews最新文献

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.

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.

Helicobacter pylori is a widespread pathogen responsible for chronic gastritis, peptic ulcers, and an elevated risk of gastric cancer. Lipopolysaccharide (LPS), localized exclusively in the outer leaflet of the outer membrane, is essential for maintaining bacterial integrity. Recent advances have deepened our understanding of H. pylori LPS structure, particularly lipid A modifications and the redefinition of the core oligosaccharide and O-antigen regions. The complete set of enzymes involved in LPS biosynthesis has been identified in the reference strain G27, and comparative genomics has revealed a notable regional difference (the absence of the heptan domain in East Asian strains). Here, we summarize recent insights into the structure and function of H. pylori LPS, emphasizing its role in bacterial persistence and its promise as a target for LPS-based glycoconjugate vaccine development.

Numerous pathogens, including viruses, enter the central nervous system and cause neurological disorders, such as encephalitis. Viruses are the main etiologic agents of such neurological diseases, and some of them cause a high death toll worldwide. Our knowledge about neuroinvasive and encephalitogenic virus infections is still limited due to the relative inaccessibility of the brain. To mitigate this shortcoming, neural ex vivo models have been developed and turned out to be of paramount importance for understanding neuroinvasive and neurotropic viruses. In this review, we describe the major ex vivo models for the central nervous system, including neural cultures, brain organoids, and organotypic brain cultures. We highlight the key findings from these models and illustrate how these models inform on viral processes, including neurotropism, neuroinvasion, and neurovirulence. We discuss the limitations of ex vivo models, highlight ongoing progress, and outline next-generation ex vivo models for virus research at the interface of neuroscience and infectious diseases.

Although a large fraction of Earth's volume and most places beyond the planet lack life because physical and chemical conditions are too extreme, intriguing scientific questions are raised in many environments within or at the edges of life's niche space in which active life is absent. This review explores the environments in which active microorganisms do not occur. Within the known niche space for life, uninhabited, but habitable physical spaces potentially offer opportunities for hypothesis testing, such as using them as negative control environments to investigate the influence of life on planetary processes. At the physico-chemical limits of life, questions such as whether spaces devoid of actively metabolizing or reproducing life constitute uninhabitable space or space containing vacant niches that could be occupied with appropriate adaptation are raised. We do not know the extent to which evolution has allowed life to occupy all niche space within its biochemical potential. The case of habitable extraterrestrial environments and the scientific and ethical questions that they raise is discussed.

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.

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.

Clostridium scindens is a keystone bacterial species in the mammalian gut that, while low in abundance, has a significant impact on bile acid and steroid metabolism. Numerous studies indicate that the two most studied strains of C. scindens (i.e. ATCC 35704 and VPI 12708) are important for a myriad of physiological processes in the host. We focus on both historical and current microbiological and molecular biology work on the Hylemon-Björkhem pathway and the steroid-17,20-desmolase pathway that were first discovered in C. scindens. Our most recent analysis now calls into question whether strains currently defined as C. scindens represent two separate taxonomic groups. Future directions include developing genetic tools to further explore the physiological role of bile acid and steroid metabolism by strains of C. scindens and the causal role of these pathways in host physiology and disease.

Leprosy, caused by Mycobacterium leprae and Mycobacterium lepromatosis, remains a significant global health issue despite a tremendous decline in its worldwide prevalence in the last four decades. Mycobacterium leprae strains possess very limited genetic variability, making it difficult to distinguish them using traditional genotyping tools. Successful genome sequencing of a considerable number of M. leprae strains in the recent past has allowed development of improved genotyping tools for the molecular epidemiology of leprosy. Comparative genomics has identified distinct M. leprae genotypes and revealed their characteristic genomic markers. This review summarizes the progress made in M. leprae genomics, with special emphasis on the development of genotyping schemes. Further, an updated genotyping scheme is introduced that also includes the newly reported genotypes 1B_Bangladesh, 1D_Malagasy, 3K-0/3K-1, 3Q and 4N/O. Additionally, genotype-specific markers (single nucleotide polymorphisms, Insertion/Deletion) have been incorporated into the typing scheme for the first time to enable differentiation of closely related strains. This will be particularly useful for geographic regions where M. leprae strains characterized by a small number of genotypes are predominant. The detailed compilation of genomic markers will also enable accurate identification of M. leprae genotypes, using targeted analysis of variable regions. Such markers are good candidates for developing artificial intelligence-based algorithms for classifying M. leprae genomic datasets.

Iron and heme are crucial for pathogenic bacteria living in the human host but are not available in free form due to their binding by iron- and heme-sequestering proteins. Porphyromonas gingivalis causes dysbiosis in the oral microbiome and is considered a keystone pathogen in the onset and progression of periodontal diseases. Its ability to infect and multiply in host cells and its presence in distant tissues and fluids highlights its pathogenic versatility and explains the relationship between periodontal diseases and systemic or neurodegenerative diseases. Porphyromonas gingivalis has evolved specialized mechanisms that allow it to thrive in the host under adverse nutrient-limited conditions. This review presents the updated summary of the mechanisms of iron and heme acquisition by P. gingivalis, with a central role played by gingipains and the unique Hmu system. The potential role of other iron and heme acquisition systems, such as Hus and Iht, indicates the importance of the partially conserved heme biosynthesis pathway, involving homologs of the HemN, HemG, and HemH proteins. In light of increasing antibiotic resistance, difficulties with diagnosis, and drug administration, targeting the mechanisms of heme and iron acquisition of P. gingivalis represents a promising target for developing diagnostic tests, preventive or therapeutic strategies.