Browsing by Author "Liu, Yao"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Diabetes mellitus promotes the nasal colonization of high virulent Staphylococcus aureus through the regulation of SaeRS two-component system
    (Taylor & Francis, 2023) Wang, Qichen; Nurxat, Nadira; Zhang, Lei; Liu, Yao; Wang, Yanan; Zhang, Lei; Zhao, Na; Dai, Yingxin; Jian, Ying; He, Lei; Wang, Hua; Bae, Taeok; Li, Min; Liu, Qian; Microbiology and Immunology, School of Medicine
    Diabetic foot infections are a common complication of diabetes. Staphylococcus aureus is frequently isolated from diabetic foot infections and commonly colonizes human nares. According to the study, the nasal microbiome analysis revealed that diabetic patients had a significantly altered nasal microbial composition and diversity. Typically, the fasting blood glucose (FBG) level had an impact on the abundance and sequence type (ST) of S. aureus in diabetic patients. We observed that highly virulent S. aureus ST7 strains were more frequently colonized in diabetic patients, especially those with poorly controlled FBG, while ST59 was dominant in healthy individuals. S. aureus ST7 strains were more resistant to human antimicrobial peptides and formed stronger biofilms than ST59 strains. Critically, S. aureus ST7 strains displayed higher virulence compared to ST59 strains in vivo. The dominance of S. aureus ST7 strains in hyperglycemic environment is due to the higher activity of the SaeRS two-component system (TCS). S. aureus ST7 strains outcompeted ST59 both in vitro, and in nasal colonization model in diabetic mice, which was abolished by the deletion of the SaeRS TCS. Our data indicated that highly virulent S. aureus strains preferentially colonize diabetic patients with poorly controlled FBG through SaeRS TCS. Detection of S. aureus colonization and elimination of colonizing S. aureus are critical in the care of diabetic patients with high FBG.
  • Thumbnail Image
    Item
    Identification of Hypoxia-ALCAMhigh Macrophage- Exhausted T Cell Axis in Tumor Microenvironment Remodeling for Immunotherapy Resistance
    (Wiley, 2024) Xun, Zhenzhen; Zhou, Huanran; Shen, Mingyi; Liu, Yao; Sun, Chengcao; Du, Yanhua; Jiang, Zhou; Yang, Liuqing; Zhang, Qing; Lin, Chunru; Hu, Qingsong; Ye, Youqiong; Han, Leng; Biostatistics and Health Data Science, School of Medicine
    Although hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elusive. This knowledge gap has hindered the development of therapeutic strategies to overcome tumor immune resistance induced by hypoxia. Here, bulk, single‐cell, and spatial transcriptomics are integrated to characterize hypoxia associated with immune escape during carcinogenesis and reveal a hypoxia‐based intercellular communication hub consisting of malignant cells, ALCAM high macrophages, and exhausted CD8+ T cells around the tumor boundary. A hypoxic microenvironment promotes binding of HIF‐1α complex is demonstrated to the ALCAM promoter therefore increasing its expression in macrophages, and the ALCAM high macrophages co‐localize with exhausted CD8+ T cells in the tumor spatial microenvironment and promote T cell exhaustion. Preclinically, HIF‐1ɑ inhibition reduces ALCAM expression in macrophages and exhausted CD8+ T cells and potentiates T cell antitumor function to enhance immunotherapy efficacy. This study reveals the systematic landscape of hypoxia at single‐cell resolution and spatial architecture and highlights the effect of hypoxia on immunotherapy resistance through the ALCAM high macrophage‐exhausted T cell axis, providing a novel immunotherapeutic strategy to overcome hypoxia‐induced resistance in cancers.
  • Thumbnail Image
    Item
    Virulence adaption to environment promotes the age-dependent nasal colonization of Staphylococcus aureus
    (Taylor & Francis, 2022) Zhao, Na; Cheng, Danhong; Yang, Ziyu; Liu, Yao; Wang, Yanan; Jian, Ying; Wang, Hua; Li, Min; Bae, Taeok; Liu, Qian; Microbiology and Immunology, School of Medicine
    Staphylococcus aureus is an important human commensal bacteria colonizing the human body, especially the nasal cavity. The nasal carriage can be a source of S. aureus bacteremia. However, the bacterial factors contributing to nasal colonization are not completely understood. By analysing S. aureus strains from the nasal cavity of the children, young adults, and seniors, we found that the low activity of the SaeRS two-component system (TCS) is an important determinant for S. aureus to colonize in seniors. The senior group isolates of S. aureus showed a rather distinct sequence type composition as compared with other age group isolates. The senior group isolates showed not only a lower gene carriage of enterotoxins a, c, and q but also lower hemolytic activity against human red blood cells. Of regulators affecting hemolysin production (i.e. agr, saeRS, rot, rsp, and sarS), only the SaeRS TCS showed an age-dependent decrease of activity. The decreased virulence and better colonization ability of the senior group isolates of S. aureus were confirmed in the mouse model. The senior group isolates showed the lowest survival and the best adhesion and colonizing ability. Also, the senior nasal secretions supported S. aureus survival better than the child and young adult nasal secretions. These results indicated that the senior nasal cavity favours colonization of S. aureus with higher adhesion and lower virulence, to which the reduced SaeRS TCS activity contributes. Taken together, our results illustrate an example of bacterial adaptation to the changing host environment.