As a representative next-generation probiotic, Akkermansia muciniphila (A. muciniphila) produces a variety of functional proteins that play critical roles in the prevention and treatment of multiple diseases, including metabolic disorders, inflammatory diseases, neurological disorders, and cancer. This review summarizes the disease-associated proteins of A. muciniphila reported to date, including the outer membrane proteins Amuc_1100 and Amuc_1098, as well as the secreted proteins P9 (Amuc_1631), P5, Amuc_1409, Amuc_1434, and Amuc_2109. These proteins exert their biological effects by activating multiple signaling pathways, such as Toll-like receptor 2 (TLR2), ICAM-2, and Wnt/β-catenin, thereby regulating physiological processes including glucagon-like peptide-1 (GLP-1) secretion, serotonin biosynthesis, lipid metabolism, and intestinal stem cell proliferation. This review provides a theoretical foundation and future perspectives for in-depth research investigation and clinical application of A. muciniphila disease-related proteins.

Chronic inflammatory diseases, closely linked to gut microbiota dysbiosis, pose a major global health burden. Akkermansia muciniphila (A. muciniphila), a key gut commensal, sustains immune homeostasis and metabolic balance, emerging as a promising next-generation probiotic. This review synthesizes current evidence on the mechanisms such as regulating the intestinal barrier, immunomodulation, mediating anti-inflammatory metabolites and regulating microbiota and therapeutic potential of A. muciniphila in inflammation-related diseases. Integrating these with experimental/clinical data across inflammation-related disorders establishes a coherent framework. Beyond live bacteria, advances in pasteurized formulations and bioactive derivatives highlight complementary advantages.

Peptidoglycan, a crucial constituent of the bacterial cell envelope, is essential for maintaining cellular integrity and morphology. Elucidating the regulatory processes that coordinate its biosynthesis and turnover not only addresses a fundamental question in microbiology but also reveals promising targets for antimicrobial drug development. This review summarizes recent advances in understanding the mechanisms governing peptidoglycan regulation, emphasizing the coordinated control of synthetic and hydrolytic pathways through multilayered networks that include transcriptional regulators, two-component systems, non-coding small RNAs, scaffold proteins, and protein-protein interactions. Building on these insights, we discuss the application of these regulatory principles in industrial biotechnology and the development of next-generation antimicrobial agents. Finally, we outline future research directions aimed at providing novel strategies to combat bacterial resistance and enhancing microbial platform engineering.

Salmonella is a foodborne pathogen that predominantly resides in the intestinal tract of humans and animals. Infections caused by Salmonella can lead to various illnesses, including gastroenteritis, bacteremia, septicemia, and focal infections, with severe cases potentially resulting in host mortality. The mechanisms by which Salmonella invades host cells and disseminates throughout the body are partly understood, but there are still many scientific questions to be solved. This review aims to synthesize existing research on the interactions between Salmonella and hosts, detailing a comprehensive infection mechanism from adhesion and invasion to intracellular propagation and systemic spread. Overuse of antibiotics contributes to the emergence of drug-resistant Salmonella strains. An in-depth analysis of the mechanism of Salmonella infection will provide a theoretical basis for the development of novel Salmonella control strategies. These innovative control strategies include antibiotic adjuvants, small molecules, phages, attenuated vaccines, and probiotic therapies, which show huge potential in controlling Salmonella infection.

Plant polyphenols, a class of natural plant products with nutritional and medicinal value, can be alternatively produced by microbial cell factories. However, metabolic cross talk and enzyme incompatibility within the microbial host limits their synthesis. Therefore, we developed a sustainability-driven biotechnological process using cytoplasm periplasm combinatorial engineering to producing salvianic acid A (SAA), a plant polyphenol derived from the roots of Salvia miltiorrhiza. SAA possesses potent cardiovascular and therapeutic benefits, but its rising demand is constrained by limited natural yields. First, we optimized an artificial SAA pathway by identifying an efficient 4-hydroxyphenyllatic acid dehydrogenase and 4-hydroxyphenyllatic acid hydroxylase, followed by improving the catalytic performance of hydroxylase. Periplasm engineering further enhanced SAA synthesis while reducing by-product formation. Additionally, cofactor engineering was applied to ensure an adequate supply of both periplasmic and cytoplasmic cofactors. The resulting strain was capable of producing up to 37.26 g L-1 of SAA, a new record in engineered microbial performance. The strategy reported here can be used for the large-scale production of other plant polyphenols and natural products.

Small RNAs (sRNAs) play crucial roles in response to environmental stress and contribute to bacterial survival. However, the understanding of sRNA response and regulatory mechanisms in Lactococcus lactis remains limited. In this study, a novel acid-activated sRNA, C263, was identified, which enhances cell wall (CW) peptidoglycan synthesis by base pairing with the mRNA 5' untranslated region (5'UTR) of murA, murC, and mraY. Additionally, it was observed that transcriptional regulator RmaE can activate sRNA C263 through binding to its promoter region at 5'-AAAATTTT-3'. This binding was also validated using a LacZ reporter system in vivo. The β-galactosidase activity of the strain carrying p-C263p-lacZ-rmaE was 4.72-fold higher than that of the control group. These findings indicate that the transcriptional regulator RmaE can activate sRNA C263 to regulate CW homeostasis in response to acid stress in L. lactis. This study offers evidence for a synergistic regulatory mechanism involving transcriptional regulators and sRNAs in the CW of L. lactis in response to acid stress. Lactococcus lactis serves as an important strain in microbial cell factories. Therefore, understanding the regulatory mechanisms of the CW is essential for advancing molecular engineering and genetic editing strategies in industrial microorganisms such as L. lactis.

The FAS cell surface death receptor, a member of the tumor necrosis factor receptor family, activates both apoptotic and non-apoptotic signaling upon interaction with its ligand FASL. It is critical in cell migration, invasion, immune responses, and carcinogenesis. Pathogen infection can influence host cells’ behavior by modulating the FAS/FASL pathway, thereby influencing disease progression. Understanding the role of FAS signaling in the context of pathogen interactions is therefore crucial. This review examines FAS-mediated apoptotic and non-apoptotic signaling pathways, with particular emphasis on the mechanisms of apoptosis and inflammation induced by bacterial and viral infections. Additionally, it highlights therapeutic strategies, including drug, cytokine, antibody, and FASL recombinant protein therapies, providing new directions for treating pathogenic infections and cancers, as well as insights into developing novel therapeutic approaches.

Salmonella is one of the most common pathogenic bacteria with a wide range of hosts and can be transmitted by various routes, infecting animals and humans and causing a range of gastrointestinal and systemic diseases. The innate immune system acts as the frontline defense against pathogenic bacteria, triggering inflammatory and antimicrobial responses by coordinating multiple signaling pathways through host pattern recognition receptors. The success of Salmonella infection is largely dependent on the host’s innate immune defense. This article reviews the process of Salmonella infection and the innate immune defense response of host cells infected with Salmonella.

α-Farnesene, a type of acyclic sesquiterpene, is an important raw material in agriculture, aircraft fuel, and the chemical industry. In this study, we constructed an efficient α-farnesene-producing yeast cell factory by combining enzyme and metabolic engineering strategies. First, we screened different plants for α-farnesene synthase (AFS) with the best activity and found that AFS from Camellia sinensis (CsAFS) exhibited the most efficient α-farnesene production in Saccharomyces cerevisiae 4741. Second, the metabolic flux of the mevalonate pathway was increased to improve the supply of the precursor farnesyl pyrophosphate. Third, inducing site-directed mutagenesis in CsAFS, the CsAFSW281C variant was obtained, which considerably increased α-farnesene production. Fourth, the N-terminal serine-lysine-isoleucine-lysine (SKIK) tag was introduced to construct the SKIK∼CsAFSW281C variant, which further increased α-farnesene production to 2.8 g/L in shake-flask cultures. Finally, the α-farnesene titer of 28.3 g/L in S. cerevisiae was obtained by fed-batch fermentation in a 5 L bioreactor.

选用人肠上皮细胞Henle-407作为模型,经鼠伤寒沙门氏菌感染后提取其分泌的外泌体,利用Label?free相对定量蛋白质组学方法探究外泌体内宿主细胞蛋白质组的变化.结果表明,在鼠伤寒沙门氏菌感染或未感染的宿主细胞外泌体中共鉴定到宿主蛋白质2490种,其中包括321种差异表达蛋白.在该321种蛋白中,共有蛋白有7种,包括3种表达上调蛋白和4种表达下调蛋白.相比于共有蛋白,314种蛋白属于非共有蛋白,即与未感染组外泌体相比,在感染组外泌体中特异性存在的宿主蛋白有9种,而缺失的宿主蛋白却多达305种.基因本体论分析表明差异蛋白主要分布于细胞器、细胞膜等细胞组分,参与代谢和生物调节等生物学过程,与结合、催化和转运等分子功能有关.京都基因与基因组百科全书分析表明差异蛋白主要富集在17种代谢通路中.通过比较鼠伤寒沙门氏菌感染与未感染组外泌体内宿主来源的蛋白质组学数据变化发现,鼠伤寒沙门氏菌感染除了改变少部分共有蛋白的表达以外,同时会导致大量宿主细胞来源的蛋白质在外泌体中急剧减少.外泌体作为一种粒径在30～150 nm的双层膜囊泡,在空间有限的情况下,推测沙门氏菌可能通过某种未知机制抑制了宿主细胞蛋白向外泌体中的转运,而沙门氏菌的特异性蛋白和脂多糖等成分进入外泌体内,通过改变邻近宿主细胞对沙门氏菌的易感性进而帮助沙门氏菌在宿主细胞中的感染和扩散.

沙门氏菌(Salmonella)污染是威胁食品安全和人体健康的主要因素之一,控制沙门氏菌污染是食品研究领域普遍关注的问题.本文综合阐述了沙门氏菌利用其生物膜的形成、耐酸耐热的特性、食品基质的差异以确保自身生存与繁殖的生存策略,并详细介绍了防控沙门氏菌的物理、化学和生物方法,以期为进一步定向调控沙门氏菌的危害、提高食品安全性提供理论指导.

Extracellular vesicles are small vesicles with a diameter of 30–150 nm that are actively secreted by eukaryotic cells and play important roles in intercellular communication, immune responses, and tumorigenesis. Previous studies have shown that extracellular vesicles are involved in the process of Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. However, changes in the protein content of extracellular vesicles elicited by S. Typhimurium infection have not been determined. Here, we extracted the extracellular vesicles with high purity from S. Typhimurium-infected Henle-407 cells, a kind of human intestinal epithelial cells, by ultracentrifugation combined with an extracellular vesicles purification kit, and analyzed their protein composition using label-free relative quantitative proteomics. The extracted extracellular vesicles exhibited an oval vesicular structure under electron microscopy, with a mean diameter of 140.4 ± 32.4 nm. The exosomal marker proteins CD9, CD63, and HSP70 were specifically detected. Compared with the uninfected group, nearly 1,234 specifically loaded proteins were uncovered in S. Typhimurium-infected Henle-407 cells. Among them were 409 S. Typhimurium-derived specific proteins, indicating a significant alteration in protein composition of extracellular vesicles by S. Typhimurium infection. Notably, these proteins included 75 secretory proteins and over 300 non-secretory proteins of S. Typhimurium, implicating novel pathways for bacterial protein delivery, although it remains unclear if their loading into extracellular vesicles is active or passive. To investigate the roles of these extracellular proteins, we exemplified the function of SopB, a well-known T3SS effector protein, and showed that the extracellular SopB could be taken up by RAW264.7 macrophages, activating the phosphorylation of Akt. This study provides new insights into the mechanism of Salmonella infection through extracellular vesicles that transport virulence proteins to uninfected neighboring cells to facilitate further infection.

Nuclear localization signals (NLS) are generally short peptides that act as a signal fragment that mediates the transport of proteins from the cytoplasm into the nucleus. This NLS-dependent protein recognition, a process necessary for cargo proteins to pass the nuclear envelope through the nuclear pore complex, is facilitated by members of the importin superfamily. Here, we summarized the types of NLS, focused on the recently reported related proteins containing nuclear localization signals, and briefly summarized some mechanisms that do not depend on nuclear localization signals into the nucleus.

细胞核是细胞遗传与代谢的控制中心,调控细胞对外界的响应、代谢、生长和分化等细胞活动.在细菌感染宿主细胞过程中,个别细菌来源的效应蛋白能够靶向进入宿主细胞核,影响细胞核内基因的转录、RNA剪切、DNA修复以及染色质重组等生命活动,将这些能够进入细胞核的细菌效应蛋白称之为核调节蛋白.对病原菌分泌的核调节蛋白进入宿主细胞核的方式,以及不同病原菌的核调节蛋白调控宿主细胞的生命过程进行归纳总结,从而为深入探究病原细菌感染宿主细胞的致病机理提供理论基础.

由食源性致病菌引发的食品安全问题是威胁人类健康的重要因素.因此,研究食源性致病菌的感染机理对于控制病原菌危害具有重要意义.[目的]以常见的食源性致病菌——鼠伤寒沙门氏菌为研究对象,以其发挥重要致病性的转录调控因子SlyA为靶标,比较胞嘧啶单碱基编辑技术(CRISPR/Cas9-guided-Cytidine Base Editor,CBE)和λ-Red同源重组技术在构建鼠伤寒沙门氏菌SlyA敲除菌株方面的方法差异,为鼠伤寒沙门氏菌的基因编辑技术应用提供数据.同时,也为其他类型病原菌的基因编辑技术开发提供有力参考.[方法]采用PCR、Golden Gate、Sanger测序等方法完成CBE系统以及λ-Red系统的构建以及敲除结果的验证,采用Editor-R软件分析CBE系统的单碱基编辑效率,采用Western blotting在蛋白表达层面对敲除结果进行验证.此外,本研究还结合了表型鉴定的方法验证了基因敲除结果.[结果]经PCR产物测序鉴定、Western blotting分析及溶血素活性鉴定等结果表明,本研究成功将CBE系统应用于鼠伤寒沙门氏菌slyA的单碱基编辑中,应用前述两种方法构建了鼠伤寒沙门氏菌SlyA敲除菌株.[结论]CBE系统虽然以其操作的简便性在基因编辑中优势明显,但同λ-Red系统相比,该方法需要设立特定的gRNA及PAM位点,在非模式菌株中的普适性较低,且在进行编辑时,CBE系统存在不稳定的问题.尽管如此,但CBE系统在鼠伤寒沙门氏菌中的成功建立,为进一步拓展与完善该菌的基因编辑系统提供了基础.

沙门氏菌是一种重要的细胞内病原体.沙门氏菌侵染宿主细胞后,可导致宿主细胞质膜内陷,形成沙门氏菌内含小泡(Salmonella-containing Vacuole,SCV),沙门氏菌能够在SCV中生存并繁殖;同时,部分沙门氏菌可从破溃的SCV中逃逸而出,游离于宿主细胞胞浆并快速繁殖,称其为超级繁殖菌.不同类型的沙门氏菌采取不同的应对措施与宿主细胞的防御机制进行斗争,通过调控宿主细胞的信号途径协助其逃避异噬的清除.该文主要综述了沙门氏菌在宿主细胞内的两种存活方式,以及两种生存方式下沙门氏菌逃避细胞异噬对病原体降解的具体机制,旨在更深入理解沙门氏菌的胞内生存机制.