The emergence of superbugs with both high pathogenicity and high antimicrobial resistance poses a major challenge to public health. In Staphylococcus aureus, α-hemolysin (Hla) is a key virulence factor mediating infection and thus represents a crucial target for prevention and control. This review first summarized the structural characteristics of Hla in its monomeric crystalline form and heptameric pore assembly. It then systematically delineated the multi-layered and fine-tuned regulation of Hla expression, involving the hla gene locus, the Agr quorum-sensing system, the Sar protein family, the Staphylococcal accessory element regulator (SaeRS) two-component system, and other auxiliary regulators. The pathogenic mechanisms of Hla were further elaborated from the perspectives of both cellular effects and host receptors. Finally, this review summarized recent advances in prevention and treatment strategies targeting Hla, including vaccines, monoclonal antibodies, natural compounds, and nanoparticles, offering new insights and candidate approaches for the precise prevention of drug-resistant S. aureus infections.

The health risks posed by pathogenic microbial contamination in drinking water are becoming increasingly apparent. Following exposure to pathogens via water, the human body may experience reactions ranging from infection and illness to death. However, the current Standards for Drinking Water Quality (GB 5749—2022) primarily rely on indicator microorganisms to evaluate water quality, lacking precise targets for pathogen control and load levels, which makes it difficult to accurately assess the actual hazards posed by microorganisms in drinking water. Therefore, clarifying the relationship between the intake dose of pathogenic microorganisms in drinking water and the risk of human infection is of great significance for safeguarding public health. Quantitative microbial risk assessment (QMRA) can be employed to evaluate the health risks posed by pathogenic microorganisms in drinking water. It is currently combined with high-throughput molecular technologies such as real-time quantitative PCR, digital quantitative PCR, metagenomics, and metaviromics, overcoming the limitations of conventional culture-based methods in identifying pathogenic hazards and demonstrating significant advantages in pathogen hazard identification and multidimensional traceability. This paper reviews the research progress in the quantitative monitoring and risk assessment of pathogenic microorganisms in drinking water. On the basis of the distribution patterns and quantitative detection of pathogenic microorganisms, QMRA is employed to conduct risk prediction, screen high-risk pathogens, and identify critical control points, and thus a systematic approach for precise prevention and control and full-chain governance is ultimately established. This approach integrates multi-omics technologies, big data analysis, and health impact assessment, achieving a transition in water quality safety management from reactive response to proactive prevention and providing robust scientific support for ensuring drinking water safety and the health of vulnerable populations.

Driven by the continuous pressure of antibiotic selection, bacteria continue to evolve through multidrug resistance mechanisms, resulting in the increasing ineffectiveness of conventional antibiotic treatment and posing a severe challenge of no drug availability in clinical practice. Nano-delivery systems breathe new life into antimicrobial therapy with their designable physicochemical properties and versatile integration characteristics. Nano-delivery systems are not limited to simple drug carriers, but can be developed into a multi-functional intelligent platform integrating precise delivery, microenvironment perception, and immune reprogramming through precision design. This review systematically expounds the construction strategy of antimicrobial nano-delivery systems, sorts out the development context from drug carrier, synergistic vector, intelligent response vector to intelligent biomimetic vector. Furthermore, this review discusses the targeted design and antimicrobial component loading strategy in detail, including conventional antibiotic synergy and new antimicrobial co-delivery. The core thesis of this paper is that the application of nano-delivery systems in specific infection scenarios (e.g., intracellular bacterial infection and biofilm-associated infection) has gone far beyond simple delivery, and instead actively regulates host immune homeostasis, synergistically enhancing antibacterial effects by regulating innate immunity (e.g., macrophage polarization and neutrophil function) and activating adaptive immunity. Finally, this paper makes an outlook on the challenges and future development directions of this field, emphasizing that through cross-scale design and multi-mechanism synergy, nano-delivery systems are expected to provide a new generation of therapeutic strategies that are efficient, safe, and less likely to induce drug resistance for drug-resistant bacterial infections.

Lipid metabolism disorders have emerged as a global health challenge, and gut microbiota dysbiosis, along with the consequent metabolic endotoxemia, are key factors promoting this pathological process. This review summarizes the molecular mechanisms by which natural active components (NACs) improve lipid homeostasis through targeted modulation of gut microecology. At the microecological intervention level, NACs optimize the microbiota structure by increasing the abundance of functional bacteria such as Bifidobacterium and Akkermansia muciniphila, while inhibiting the proliferation of opportunistic pathogens like Desulfovibrio. At the “metabolite-host” interaction level, the lipid-lowering mechanisms mainly involve two aspects. The first is the targeted effects of metabolites, wherein short-chain fatty acids, secondary bile acids, and phenolic acid derivatives specifically modulate metabolic targets including 3-hydroxy-3-methylglutaryl-coenzyme A reductase and fatty acid synthase. The second is the host signaling responses, wherein the aforementioned metabolic mediators synergistically modulate key signaling nodes, such as adenosine 5′-monophosphate-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptors (PPARs), to inhibit de novo lipogenesis and promote fatty acid β-oxidation, while simultaneously inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway to alleviate inflammation-associated abnormal lipid deposition. The “component-microbiota-metabolite-host signaling” regulatory mechanism outlined herein provides a theoretical reference for elucidating the pharmacodynamic material basis of NACs and developing gut microecology-based personalized nutritional intervention strategies.

The skin microbiota refers to a complex ecosystem composed of diverse microorganisms that colonize the skin, which contributes to the maintenance of skin health through interactions with the host. Studies have demonstrated that an imbalanced skin microecology can cause various skin health problems through multiple pathways, such as the induction of DNA damage in skin cells and the promotion of pro-inflammatory factor secretion. In recent years, numerous studies have confirmed that probiotics play a significant role in improving skin health, with mechanisms including antioxidation, immunomodulation, and enhancement of skin barrier function. This review comprehensively summarized the composition of the skin microecology, its role in maintaining normal skin functions, and the research progress on the pathological mechanisms of skin problems induced by microecological imbalance. Based on this, this review systematically summarized the mechanisms and research progress of microecological therapy, particularly probiotics, in improving various skin health problems, especially skin cancer, skin inflammation and photoaging, aiming to provide a theoretical basis for the exploration of the mechanisms and application of probiotics in improving skin health.

Conventional cell culture relies on serum, which has the problems of unclear composition, high cost, and contamination risks. Microbial-derived additives, with clear sources, low costs, safe components, and obvious pro-proliferative effects, have become an ideal alternative to serum in cell culture. To provide a basis for the development of new sources for the culture media of cells in agricultural production, this review first summarizes the role of microbial-derived additives in the research and development of serum-free media, and then elaborates on the application status of microbial-derived additives in cellular agriculture. On this basis, it probes into the mechanisms through which microbial-derived additives provide precision nutrition and promote cell proliferation. This review aims to provide technical support for the research and development of serum-free culture media, the establishment of cellular precision nutrition, and the sustainable development of cellular agriculture.

The arms race between bacteria and phages has driven the evolution of diverse antiphage defense systems. In recent years, a series of defense mechanisms targeting the nucleotide pool have been discovered, revealing that nucleotides are not only fundamental molecules for metabolism but also serve as key signaling carriers, effector substrates, and toxic weapons in bacterial immunity. According to the interaction modes between defense mechanisms and the nucleotide pool, this review systematically summarizes seven representative antiphage systems and categorizes them into three major classes: (1) Systems mediated by nucleotide cyclization into signaling molecules [e.g., cyclic oligonucleotide-based antiphage signaling system (CBASS), pyrimidine cyclase system for antiphage resistance (Pycsar), and Panoptes], which utilize nucleotidyltransferases to synthesize cyclic oligonucleotide second messengers that activate downstream effector proteins, leading to abortive infection; (2) Systems mediated by nucleotide depletion [e.g., deoxycytidine triphosphate (dCTP) deaminase, deoxyguanosine triphosphatase (dGTPase), and Nezha], which specifically hydrolyze or modify dNTPs or NAD⁺, resulting in a nucleotide pool imbalance and an energy crisis that block phage replication; (3) Systems mediated by aberrant nucleotide conversion [e.g., restriction by an adenosine deaminase acting on RNA (RADAR) and type III CRISPR-Cas-associated deaminase (CAAD)], which convert canonical nucleotides into toxic analogs [e.g., inosine triphosphate (ITP) and deoxyinosine triphosphate (dITP)], poisoning the nucleotide pool and inducing abortive infection. This review focuses on the core components, protein structural features, assembly mechanisms, and antiphage regulatory strategies of each category of system and discusses the escape mechanisms evolved by phages against these systems. In summary, the regulation of nucleotide pool homeostasis has emerged as a core strategy in bacterial immunity. In-depth investigation of these systems not only helps elucidate the molecular basis of prokaryote-phage co-evolution but also provides important insights for developing novel antimicrobial strategies and tools in synthetic biology.

Antibiotics in water environments, one of the major global environmental problems, pose serious ecological and health risks, necessitating efficient removal strategies. Microalgae-bacteria systems have recently emerged as a promising approach for antibiotic removal due to their high efficiency, strong removal capacity, simple design, easy operation, and low costs. This review systematically summarizes recent advances in the removal of antibiotics by microalgae-bacteria systems. First, it introduces the current status of antibiotic pollution and its effects on the environment. Second, it elaborates on the interaction mechanisms between microalgae and bacteria, which include nutrient exchange, signal transduction, and gene transfer. Then, it analyzes the application of microalgae-bacteria systems in the degradation of antibiotics, involving the degradation effects and pathways for different types of antibiotics. Finally, this paper discusses the responses of bacteria and microalgae under antibiotic stress, including the changes in short-term and long-term physiological metabolic adaptation, and analyzes the key factors influencing the antibiotic removal performance of microalgae-bacteria systems.

Alcoholic liver disease (ALD) is one of the most common types of chronic liver diseases globally and an important cause of liver cirrhosis and liver cancer. Currently, the diagnosis and treatment of ALD face challenges such as delayed diagnosis, poor compliance with alcohol abstinence, and a lack of specific drugs. Therefore, it is of great significance to develop new intervention strategies. In recent years, the intervention effect of the medicinal herb Salvia miltiorrhiza (Sal) on ALD has received extensive attention. The crude extracts and active components of Sal can alleviate the pathological process of ALD through anti-inflammatory and lipid metabolism regulation, while the efficacy of single Sal treatment has limitations. Thus, combination medication has become an important strategy for ALD treatment. This article reviews the research progress in the combination strategies of Sal with natural products, antioxidants, liver-protecting drugs, and microecological regulators in the intervention of ALD. It is found that the combination medication with Sal can regulate the abundance of the gut microbiota and play a synergistic liver-protecting role through the mediation of gut microbiota. Relevant studies have confirmed that microecological regulators such as probiotics, prebiotics, postbiotics, and synbiotics can also ameliorate ALD by regulating the “gut-liver axis”, and they can be combined with Sal to intervene in ALD, demonstrating good clinical prospects. Developing microecological regulators targeting the gut microbiota homeostasis in ALD can not only provide new ideas for the development of bioactive preparations with high efficiency and low toxicity, but also have potential clinical value in improving the therapeutic efficacy and prognosis for ALD. It is an important research and development direction for new combination intervention strategies with Sal for ALD in the future.

Citrus is one of the most important economic crops in China at present. During the cultivation, it is threatened by multiple diseases. Citrus canker, as the most common disease in citrus cultivation, has caused great harm to the development of the citrus industry. The long-term use of chemical control agents has led to problems such as enhanced resistance of pathogenic bacteria, chemical residues on the surface of citrus fruits, and environmental pollution. Microbial control has attracted increasing attention due to its safety and pollution-free advantages. This review summarizes the sources and species of biocontrol microorganisms for citrus canker in the past decade, analyzes the biocontrol mechanisms of these microorganisms, evaluates the development and field control effects of biocontrol agents, and points out the problems existing in the microbial control of citrus canker, providing a reference for the research on biocontrol microorganisms for citrus canker.