Xinyue Yao

Nanjing General Hospital of Nanjing Military Command

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Fuquan Hu

Bethel University

Yan Zhao

Ji Hua Laboratory

Jing Wang

Zhejiang A & F University

Yinling Tan

Army Medical University

Jiaqi Tang

Northeast Agricultural University

Xiancai Rao

Army Medical University

Xuefang Xu

Yanshan University

Jing Wang

Guilin University of Technology

Ailan Zhao

National Institute for Communicable Disease Control and Prevention

Yanwen Xiong

National Institute for Communicable Disease Control and Prevention

Cooperative Institutions

Army Medical University

National Institute for Communicable Disease Control and Prevention

Chinese Center For Disease Control and Prevention

Center for Disease Control

State Key Laboratory of Infectious Disease Prevention and Control

Nanjing University

Nanjing General Hospital of Nanjing Military Command

Nanjing Medical University

Southwest Hospital

Chinese Academy of Sciences

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Isolation and characterization of a native avirulent strain of Streptococcus suis serotype 2: a perspective for vaccine development

Scientific Reports (2015)

Xinyue Yao Ming Li Jing Wang Changjun Wang Dan Hu

Abstract Streptococcus suis , an emerging infectious pathogen, is the cause of two large-scale outbreaks of human streptococcal toxic shock syndrome in China and has attracted much attention from the scientific community. The genetic basis of its pathogenesis remains enigmatic and no effective prevention measures have been established. To better understand the virulence differentiation of S. suis and develop a promising vaccine, we isolated and sequenced a native avirulent S. suis strain (05HAS68). Animal experiments revealed that 05HAS68 is an avirulent strain and could protect piglets from the attack of virulent strains. Comparative genomics analyses demonstrated the genetic basis for the lack of virulence in 05HAS68, which is characterized by the absence of some important virulence-associated factors and the intact 89K pathogenicity island. Lack of virulence was also illustrated by reduced survival of 05HAS68 compared to a virulent strain in pig whole blood. Further investigations revealed a large-scale genomic rearrangement in 05HAS68, which was proposed to be mediated by transposase genes and/or prophages. This genomic rearrangement may have caused the genomic diversity of S. suis and resulted in biological discrepancies between 05HAS68 and highly virulent S. suis strains.

Streptococcus suis

Isolation

Strain (injury)

10.1038/srep09835

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Citations (22)

Chromosomal DNA deletion confers phage resistance to Pseudomonas aeruginosa

Scientific Reports (2014)

Shuai Le Xinyue Yao Shuguang Lu Yinling Tan Xiancai Rao

Bacteria develop a broad range of phage resistance mechanisms, such as prevention of phage adsorption and CRISPR/Cas system, to survive phage predation. In this study, Pseudomonas aeruginosa PA1 strain was infected with lytic phage PaP1 and phage-resistant mutants were selected. A high percentage (~30%) of these mutants displayed red pigmentation phenotype (Red mutant). Through comparative genomic analysis, one Red mutant PA1r was found to have a 219.6 kb genomic fragment deletion, which contains two key genes hmgA and galU related to the observed phenotypes. Deletion of hmgA resulted in the accumulation of a red compound homogentisic acid; while A galU mutant is devoid of O-antigen, which is required for phage adsorption. Intriguingly, while the loss of galU conferred phage resistance, it significantly attenuated PA1r in a mouse infection experiment. Our study revealed a novel phage resistance mechanism via chromosomal DNA deletion in P. aeruginosa.

Lytic cycle

Homogentisic acid

Phagemid

10.1038/srep04738

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Citations (103)

Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

Scientific Reports (2016)

Li‐Wen Hu Xinyue Yao Yi Shen

Abstract Accumulating epidemiological evidence indicates that the quantitative changes in human mitochondrial DNA (mtDNA) copy number could affect the genetic susceptibility of malignancies in a tumor-specific manner, but the results are still elusive. To provide a more precise estimation on the association between mtDNA copy number and risk of diverse malignancies, a meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95% confidence intervals (95% CI). A total of 36 case-control studies involving 11,847 cases and 15,438 controls were finally included in the meta-analysis. Overall analysis of all studies suggested no significant association between mtDNA content and cancer risk (OR = 1.044, 95% CI = 0.866–1.260, P = 0.651). Subgroup analyses by cancer types showed an obvious positive association between mtDNA content and lymphoma and breast cancer (OR = 1.645, 95% CI = 1.117–2.421, P = 0.012; OR = 1.721, 95% CI = 1.130–2.622, P = 0.011, respectively), and a negative association for hepatic carcinoma. Stratified analyses by other confounding factors also found increased cancer risk in people with drinking addiction. Further analysis using studies of quartiles found that populations with the highest mtDNA content may be under more obvious risk of melanoma and that Western populations were more susceptible than Asians.

Quartile

10.1038/srep35859

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Citations (87)

Identification of ferroptosis-related genes for overall survival prediction in hepatocellular carcinoma

Scientific Reports (2022)

Lianxiang Luo Xinyue Yao Jing Xiang Fangfang Huang Hui Luo

Abstract Ferroptosis is a novel type of cell death depending on iron and is strongly related to the development of tumors. Hepatocellular carcinoma (HCC) is a malignancy with high incidence. Despite some reports demonstrating the relation between ferroptosis-related genes and HCC, more details have not been excavated. In the present study, we collected and analyzed HCC patients' datasets from the TCGA-LIHC project and ICGC portal, respectively. Through the bioinformatic methods, we screened 126 differentially expressed genes. Then a prognostic model was established with four genes (GPX2, MT3, PRDX1, and SRXN1). PRDX1 is the hub gene of the prognosis model and has a high expression in hepatocellular carcinoma tumor tissue and cell lines. We further found that silencing PRDX1 increased the accumulation of ferrous ions and lipid peroxidation accumulation in HEPG2 cells and promoted ferroptosis in hepatocellular carcinoma. In conclusion, the study demonstrated the four-gene signature can be used to predict HCC prognosis. It also revealed the potential function of the ferroptosis-related gene PRDX1 in HCC, which can be a biomarker of the prediction for HCC outcome.

Liver Cancer

10.1038/s41598-022-14554-7

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Citations (20)

Global Transcriptional and Phenotypic Analyses of Escherichia coli O157:H7 Strain Xuzhou21 and Its pO157_Sal Cured Mutant

PLoS ONE (2013)

Hongqing Zhao Chen Chen Yanwen Xiong Xuefang Xu Ruiting Lan

Escherichia coli O157:H7 is an important food-borne pathogen that can cause hemorrhagic colitis and hemolytic-uremic syndrome in humans. pO157_Sal, a novel conjugative plasmid is present in a Chinese O157:H7 outbreak strain Xuzhou21. Here we investigated the phenotypic and transcriptional differences between the wild type strain Xuzhou21 and the pO157_Sal cured mutant strain Xuzhou21m. RNA-Seq analysis found that all 52 ORFs encoded on pO157_Sal were transcribed. One hundred and sixty eight chromosomal and pO157 genes were differentially expressed (≥2 fold difference) between Xuzhou21 and Xuzhou21m. Sixty-seven and 101 genes were up-regulated and down-regulated respectively by pO157_Sal including genes related to stress response, adaption and virulence. The plasmid-cured mutant Xuzhou21m grew slower than wild type Xuzhou21 and pO157_Sal plasmid complemented strain Xuzhou21c in M9 medium under the condition of high NaCl or presence of sodium deoxycholate (NaDC), corroborating with the RNA-Seq data. Seven differentially expressed genes are associated with NaDC resistance, including the adenine-specific DNA-methyltransferase gene (dam), multidrug efflux system subunit gene mdtA, hyperosmotically inducible periplasmic protein gene osmY and oxidation-reduction related genes while two differentially expressed genes (osmY and pspD) are likely to be related to resistance to osmotic pressure. A number of differentially expressed genes were virulence associated including four genes encoding T3SS effectors from the chromosome and ehxD from pO157. Through complementation of Xuzhou21m with a plasmid construct carrying the pO157_Sal hha homolog we further showed that the pO157_Sal hha represses the expression of T3SS effectors. These findings demonstrated that the plasmid pO157_Sal affects the transcription of the chromosomal and pO157 plasmid genes and contributes to the enhanced ability to resist stress. We conclude that pO157_Sal plays an important role in regulating global gene expression and affects the virulence and adaptation of E. coli O157:H7.

10.1371/journal.pone.0065466

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Citations (13)

Subtilisin-like protease-1 secreted through type IV secretion system contributes to high virulence of Streptococcus suis 2

Scientific Reports (2016)

Supeng Yin Ming Li Xiancai Rao Xinyue Yao Qiu Zhong

Abstract Streptococcus suis serotype 2 is an emerging zoonotic pathogen that triggered two outbreaks of streptococcal toxic shock syndrome (STSS) in China. Our previous research demonstrated that a type IV secretion system (T4SS) harbored in the 89K pathogenicity island contributes to the pathogenicity of S. suis 2. In the present study, a shotgun proteomics approach was employed to identify the effectors secreted by T4SS in S. suis 2 and surface-associated subtilisin-like protease-1 (SspA-1) was identified as a potential virulence effector. Western blot analysis and pull-down assay revealed that SspA-1 secretion depends on T4SS. Knockout mutations affecting sspA-1 attenuated S. suis 2 and impaired the pathogen’s ability to trigger inflammatory response in mice. And purified SspA-1 induced the secretion of IL-6, TNF-α and IL-12p70 in THP-1 cells directly. SspA-1 is the first T4SS virulence effector reported in Gram-positive bacteria. Overall, these findings allow us to gain further insights into the pathogenesis of T4SS and STSS.

Pathogenicity island

Streptococcus suis

Virulence factor

10.1038/srep27369

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Citations (24)