A high-fat diet (HFD) is a high-risk factor for the malignant progression of cancers through the disruption of the intestinal microbiota. However, the role of the HFD-related gut microbiota in cancer development remains unclear. This study found that obesity and obesity-related gut microbiota were associated with poor prognosis and advanced clinicopathological status in female patients with breast cancer. To investigate the impact of HFD-associated gut microbiota on cancer progression, we established various models, including HFD feeding, fecal microbiota transplantation, antibiotic feeding, and bacterial gavage, in tumor-bearing mice. HFD-related microbiota promotes cancer progression by generating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, the HFD microbiota released abundant leucine, which activated the mTORC1 signaling pathway in myeloid progenitors for PMN-MDSC differentiation. Clinically, the elevated leucine level in the peripheral blood induced by the HFD microbiota was correlated with abundant tumoral PMN-MDSC infiltration and poor clinical outcomes in female patients with breast cancer. These findings revealed that the “gut–bone marrow–tumor” axis is involved in HFD-mediated cancer progression and opens a broad avenue for anticancer therapeutic strategies by targeting the aberrant metabolism of the gut microbiota.

Bacillus safensis strains have emerged as versatile microbial platforms for bioproduction, combining the benefits of probiotic utility and biocontrol. In this study, we describe the isolation and in-depth characterization of a previously unreported B. safensis strain, LG01. The genome of this strain comprises a circular chromosome encoding 13 secondary metabolite biosynthetic gene clusters, 144 carbohydrate-active enzymes, 2 antibiotic resistance loci, and 1 prophage region, indicative of strong antimicrobial and metabolic capacity. Its protein secretion systems support nutrient acquisition, colonization, quorum sensing, and antibiotic synthesis. Our phenotypic assays confirmed the antifungal and antibacterial activity, proteolytic and cellulolytic functions, and robust biofilm formation of the strain. By performing a comparative genomic analysis, we identified 78 strain-specific genes enriched in the bacteriocin immunity and sporulation pathways. Signals of positive selection in the membrane and transcriptional regulator genes further reflect the adaptive evolution underlying the strain’s ecological fitness. Together, these findings advance our understanding of the genomic features of B. safensis LG01 and highlight its promise as a candidate for biocontrol and probiotic applications.

Legionella pneumophila , the causative agent of Legionnaires’ disease, utilizes a type IV secretion system (T4SS) to translocate effectors into host cells, modulating diverse cellular processes to create a replication-permissive niche. Here, we characterize Ceg10, a T4SS-translocated effector, as a nucleus-targeting acetyltransferase that interferes with host ribosome biogenesis and cell cycle progression. Structural analysis reveals that Ceg10 harbors a conserved Cys-His-Asp (CHD) catalytic triad required for its acetyltransferase activity. Upon nuclear import mediated by the host transport adaptor HEATR3, Ceg10 selectively acetylates the ribosomal protein RPS20 at Thr64, Thr65, and Arg66, which have not been annotated as posttranslational modification sites. This acetylation impairs RPS20’s interaction with RPS29 and 18S rRNA, two components critical for 40S ribosomal subunit assembly, leading to translation inhibition and G1/S cell cycle arrest. These host perturbations are essential for efficient early-stage intracellular replication of L. pneumophila . Our findings identify a distinct mechanism by which a bacterial effector co-opts nuclear import machinery and directly modifies ribosomal proteins to subvert host biosynthesis and cell cycle control, highlighting ribosomal protein acetylation as a hitherto unrecognized role in host–pathogen interactions.

Beibei Zhao, Shiyu He, Minjun Huang, Yongjun Lu, and Zhenhuang Ge. J. Microbiol. Biotechnol. 2025;35:1-11. https://doi.org/10.4014/jmb.2507.07056

Background: Limosilactobacillus reuteri is recognized for its diverse host-beneficial functions, though these are highly strain-specific. This study aimed to genomically and functionally characterize two novel L. reuteri isolates to assess their potential for specific health-associated applications. Methods: We isolated and genomically sequenced two novel L. reuteri strains, LLR2 and LLR3. Their functional potential was systematically evaluated through in vitro assays, including assessment of reuterin production, the ability to stimulate mucin production in co-culture with intestinal epithelial LS174T cells, and anti-inflammatory activity in a human brain microvascular endothelial cell (hCMEC/D3) model of LPS-induced inflammation. Results: Comparative genomic analysis revealed distinct genetic architectures between LLR2 and LLR3, reflecting divergent evolutionary trajectories. Functionally, pronounced strain-specific differences were observed: LLR3 produced the antimicrobial compound reuterin, while LLR2 did not. In co-culture with LS174T cells, both strains decrease the production of Mucin-2, a key component of the gut barrier, with LLR2 showing significantly greater efficacy. Conversely, in the hCMEC/D3 inflammation model, LLR3 demonstrated a significantly stronger anti-inflammatory effect, suppressing the LPS-induced expression of IL-6 and TNF- α . Conclusion: This study expands the genomic repository of L. reuteri and provides clear experimental evidence of strain-specific functional profiles. Our findings establish a foundation for the precision selection of L. reuteri strains such as LLR2 for gut barrier reinforcement and LLR3 for inflammation modulation in tailored applications for gut health and gut-brain axis research.