Article
Microbiology
Can Huang, Jiao Meng, Wenqian Li, Jingyu Chen
Summary: This study investigated the role of stringent response in Yersinia enterocolitica, a typical foodborne pathogen, and found that (p)ppGpp and DksA have synergistic and independent roles in regulating gene expression and phenotypes of Y. enterocolitica. Gene expression analysis revealed that (p)ppGpp and DksA deficiency reduced the transcription of flagellar synthesis genes and biofilm synthesis genes, which could potentially contribute to changes in motility and biofilm formation.
MICROBIOLOGY SPECTRUM
(2022)
Review
Microbiology
Gert Bange, Ditlev E. Brodersen, Anastasia Liuzzi, Wieland Steinchen
Summary: Under stressful growth conditions and nutrient starvation, bacteria adapt by synthesizing signaling molecules that profoundly reprogram cellular physiology, with (p)ppGpp playing a key role in this process. The synthesis and hydrolysis of this signaling molecule are carried out by specific enzymes, directly impacting intracellular effectors. Studies have revealed both common features and differences in the effects of (p)ppGpp on gram-negative and gram-positive bacteria.
ANNUAL REVIEW OF MICROBIOLOGY, VOL 75, 2021
(2021)
Article
Cell Biology
Chao-Chieh Lin, Chien-Kuang Cornelia Ding, Tianai Sun, Jianli Wu, Kai-Yuan Chen, Pei Zhou, Jen-Tsan Chi
Summary: All organisms have developed stress adaptive strategies to maintain homeostasis. Bacteria rely on the stringent response triggered by (p)ppGpp, while metazoans possess MESH1 as a ppGpp hydrolase. Knockdown of MESH1 in human cancer cells induces ER stress and ISR, with ATF4 playing a key role in mediating the stress survival response and ferroptosis regulation.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Abhimanyu K. Singh, Sergio E. Martinez, Weijie Gu, Hoai Nguyen, Dominique Schols, Piet Herdewijn, Steven De Jonghe, Kalyan Das
Summary: The authors discovered a transient P-pocket created by HIV reverse transcriptase while sliding over a DNA substrate and developed a cryo-EM platform for lead optimization. By screening 300 drug-like fragments, they identified two leads that bind to the P-pocket, which is resilient to drug-resistance mutations and composed of structural elements from polymerase active site, primer grip, and template-primer. An engineered RT/DNA aptamer complex was utilized to trap the transient P-pocket and structures of the RT/DNA complex in the presence of an inhibitory fragment were determined.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Danye Qiu, Esther Lange, Thomas. M. M. Haas, Isabel Prucker, Shinji Masuda, Yan. L. L. Wang, Georg Felix, Gabriel Schaaf, Henning. J. J. Jessen
Summary: Nucleotides (p)ppGpp play important roles as signaling molecules in bacteria and plants. In this study, the researchers used CE-MS to analyze the abundance and composition of ppGpp in Arabidopsis thaliana and found a significant increase of ppGpp levels upon infection with the bacteria pathogen Pseudomonas syringae pv. tomato (PstDC3000), stimulated by the flagellin peptide flg22. This increase is dependent on the functional flg22 receptor FLS2 and its interacting kinase BAK1, indicating that PAMP receptor-mediated signaling controls ppGpp levels.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biology
Anurag Kumar Sinha, Kristoffer Skovbo Winther
Summary: This study reveals that bacteria synthesize (p)ppGpp to reprogram cell physiology in response to environmental stresses, with proteins of the RSH superfamily playing a key role in hydrolyzing or synthesizing (p)ppGpp. The inactive hydrolase domain of Escherichia coli RelA modulates the activity of the synthetase domain, and mutagenesis studies identify a loop region in the hydrolase domain that acts as a molecular switch to regulate synthetase activity.
COMMUNICATIONS BIOLOGY
(2021)
Article
Microbiology
Amy Ontai-Brenning, Randy Hamchand, Jason M. Crawford, Andrew L. Goodman
Summary: Mammals exhibit daily fasting and feeding patterns that affect the gut environment. The gut commensal Bacteroides thetaiotaomicron uses ppGpp to adapt to the host's feeding cycle and maintain population size during the fasting phase. ppGpp is also important for colonization of the mucous layer during the fasting phase.
Article
Biochemistry & Molecular Biology
Can Huang, Wenqian Li, Jingyu Chen
Summary: The stringent response is a rapid response system found in bacteria that enables them to sense and adapt to changes in the external environment. The regulators (p)ppGpp and DksA play complex roles in gene regulation, affecting various cellular functions such as motility, antibiotic resistance, biofilm formation, and metabolic processes. Through gene expression analysis, this study provides insights into the regulatory networks controlled by (p)ppGpp and DksA, shedding light on their involvement in ribosomal synthesis, energy metabolism, amino acid transport and synthesis, as well as chemotaxis in Y. enterocolitica.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Xin Wang, Yiluo Cheng, Wenting Zhang, Qin Lu, Guoyuan Wen, Qingping Luo, Huabin Shao, Zishu Pan, Tengfei Zhang
Summary: A mutant lacking (p)ppGpp synthetases in Salmonella Pullorum showed reduced ability to form biofilms and resistance to environmental stresses, as well as decreased internalization into host cells and colonization abilities in young chickens. RNA sequencing revealed that (p)ppGpp synthetases not only affected the stringent response, but also controlled the expression of virulence factors, indicating their importance for the pathogenicity of S. Pullorum.
MICROBIOLOGICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Zhining Sun, Rigumula Wu, Bin Zhao, Rilee Zeinert, Peter Chien, Mingxu You
Summary: A RNA-based fluorescent sensor has been developed for live-cell imaging of (p)ppGpp, allowing direct monitoring of cellular accumulation and dynamics of (p)ppGpp levels. These sensors provide unprecedented information on cell-to-cell variation and can be broadly adapted to study bacterial stringent response.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
Xinguang Cao, Rui Li, Huihua Xiong, Jinfang Su, Changqing Guo, Tianqi An, Hong Zong, Ruihua Zhao
Summary: Among the four Pt(IV) complexes, complex 14 shows promising potential in reversing cisplatin resistance and enhancing anticancer efficiency through multiple mechanisms. Its low systematic toxicity makes it a potential novel P-gp-mediated MDR modulator with increased tumor inhibition compared to cisplatin and oxaliplatin.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Monika Karczewska, Patryk Strzelecki, Krystyna Bogucka, Katarzyna Potrykus, Agnieszka Szalewska-Palasz, Dariusz Nowicki
Summary: Urinary tract infections are common bacterial diseases worldwide, with UPECs being the most prominent group among the pathogens responsible. In this study, we examined 118 UPEC isolates to determine their genetic background, antibiotic resistance, and their ability to form biofilms and induce stress responses. Our findings showed that these UPEC strains expressed unique attributes and had a significant ability to form biofilms and accumulate multi-resistance traits, which were crucial for the development of severe infections in a Galleria mellonella model.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Grace Kago, Charles L. Turnbough Jr, Juan Carlos Salazar, Shelley M. Payne
Summary: This study reveals the importance of (p)ppGpp synthesis in the virulence and adaptation of Shigella flexneri. Disrupting (p)ppGpp synthesis diminishes the expression of key virulence genes, reduces bacterial invasion and intercellular spread. The study also highlights the role of (p)ppGpp in maintaining the infection and spread of S. flexneri in the intracellular environment.
INFECTION AND IMMUNITY
(2023)
Article
Biochemistry & Molecular Biology
Jonathan Jagodnik, Brian Tjaden, Wilma Ross, Richard L. Gourse
Summary: Ligand-binding RNAs, known as RNA aptamers, are abundant in all three domains of life and play a role in sensing metabolites and small molecules. This study introduces a method called RNA-DRaCALA, which allows for the rapid screening of numerous RNA aptamers by examining their ligand binding. Using this method, 30 RNA aptamers were screened for their ability to bind (p)ppGpp, and key features distinguishing between ppGpp and pppGpp binding sites were identified. Additionally, the method was shown to be effective in analyzing binding of aptamers with thiamine pyrophosphate.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Microbiology
Philippe Vogeleer, Fabien Letisse
Summary: This study elucidates the mechanisms of the stringent response in Pseudomonas putida and demonstrates that (p)ppGpp can rapidly remodel the metabolic pathways in this bacterium. These findings provide an important resource for future research on the stringent response.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Immunology
Yanmeng Chen, Bocun Shen, Xiaochuan Zheng, Quanxin Long, Jie Xia, Yao Huang, Xuefei Cai, Deqiang Wang, Juan Chen, Ni Tang, Ailong Huang, Yuan Hu
EMERGING MICROBES & INFECTIONS
(2020)
Article
Microbiology
Junqi Xu, Yu Chen, Xi Mou, Yu Huang, Shuang Ma, Liyuan Zhang, Yuan Zhang, Quanxin Long, Md Kaisar Ali, Jianping Xie
FUTURE MICROBIOLOGY
(2020)
Article
Immunology
Xue-fei Cai, Juan Chen, Jie-li Hu, Quan-xin Long, Hai-jun Deng, Ping Liu, Kai Fan, Pu Liao, Bei-zhong Liu, Gui-cheng Wu, Yao-kai Chen, Zhi-jie Li, Kun Wang, Xiao-li Zhang, Wen-guang Tian, Jiang-lin Xiang, Hong-xin Du, Jing Wang, Yuan Hu, Ni Tang, Yong Lin, Ji-hua Ren, Lu-yi Huang, Jie Wei, Chun-yang Gan, Yan-meng Chen, Qing-zhu Gao, A-mei Chen, Chang-long He, Dao-Xin Wang, Peng Hu, Fa-Chun Zhou, Ai-long Huang, De-qiang Wang
JOURNAL OF INFECTIOUS DISEASES
(2020)
Article
Immunology
Mao Binli, Wang Zhuo, Pi Sidie, Long Quanxin, Chen Ke, Cui Jing, Huang Ailong, Hu Yuan
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2020)
Article
Gastroenterology & Hepatology
Sheng-Tao Cheng, Jie-Li Hu, Ji-Hua Ren, Hai-Bo Yu, Shan Zhong, Vincent Kam Wai Wong, Betty Yuen Kwan Law, Wei-Xian Chen, Hong-Mei Xu, Zhen-Zhen Zhang, Xue-Fei Cai, Yuan Hu, Wen-Lu Zhang, Quan-Xin Long, Fang Ren, Hong-Zhong Zhou, Ai-Long Huang, Juan Chen
Summary: A novel small molecule targeting HBx was identified to combat chronic HBV infection, and it was revealed that NQO1 plays a role in HBV replication by regulating the stability of HBx protein.
JOURNAL OF HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Nan Xiao, Meng Nie, Huanhuan Pang, Bohong Wang, Jieli Hu, Xiangjun Meng, Ke Li, Xiaorong Ran, Quanxin Long, Haijun Deng, Na Chen, Shao Li, Ni Tang, Ailong Huang, Zeping Hu
Summary: Metabolomic data and cytokine/chemokine profiling from stratified COVID-19 patients suggest a correlation between arginine, tryptophan, and purine metabolic pathways with hyperinflammation, potentially offering therapeutic targets for severe COVID-19 patients. Modulating metabolism can significantly impact the release of proinflammatory cytokines by peripheral blood mononuclear cells, indicating a potential strategy for treating fatal cytokine release syndrome in COVID-19.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Quan-Xin Long, Yan-Jun Jia, Xin Wang, Hai-Jun Deng, Xiao-Xia Cao, Jun Yuan, Liang Fang, Xu-Rong Cheng, Chao Luo, An-Ran He, Xiao-Jun Tang, Jie-li Hu, Yuan Hu, Ni Tang, Xue-Fei Cai, De-Qiang Wang, Jie Hu, Jing-Fu Qiu, Bei-Zhong Liu, Juan Chen, Ai-long Huang
Summary: This study evaluated the durability of protective immune responses in individuals recovered from asymptomatic or symptomatic SARS-CoV-2 infection approximately 6 months prior. Memory B cell response specific to the RBD of SARS-CoV-2 was relatively low, while T cell responses were observed in individuals recovered from COVID-19, and cross-reactive T cell responses were detected in healthy controls.
Article
Microbiology
Wenlin Ren, Jun Lan, Xiaohui Ju, Mingli Gong, Quanxin Long, Zihui Zhu, Yanying Yu, Jianping Wu, Jin Zhong, Rong Zhang, Shilong Fan, Guocai Zhong, Ailong Huang, Xinquan Wang, Qiang Ding
Summary: This study found that the Y453F mutation in miSARS-CoV-2 enhances the virus's ability to bind to mink ACE2 receptors without compromising its ability to use human ACE2 receptors. Additionally, the Y453F spike shows resistance to convalescent serum, posing a risk for vaccine development.
Article
Microbiology
Wenlin Ren, Xiaohui Ju, Mingli Gong, Jun Lan, Yanying Yu, Quanxin Long, Devin J. Kenney, Aoife K. O'Connell, Yu Zhang, Jin Zhong, Guocai Zhong, Florian Douam, Xinquan Wang, Ailong Huang, Rong Zhang, Qiang Ding
Summary: The SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta), and B.1.618, recently identified in India, have shown increased transmissibility and evasive immune properties. These variants exhibit enhanced binding affinity with ACE2 orthologs in mice, marmosets, and koalas, while still using human ACE2 with no or slightly increased efficiency. The P681R mutation in these variants facilitates spike cleavage and viral entry. Additionally, the mutations E484Q, T478K, Delta 145-146, or E484K reduce their sensitivity to neutralizing antibodies but they remain sensitive to entry inhibitors like ACE2-Ig decoy receptor. These findings highlight the rapid spread of these variants and suggest the potential use of ACE2-Ig as a broad-spectrum antiviral strategy.
Article
Biochemistry & Molecular Biology
Zongqi Shi, Huizhi Zheng, Miaomiao Han, Jieli Hu, Yuan Hu, Xiaosong Li, Wenyan Zhu, Xinjun He, Haijun Deng, Quanxin Long, Ailong Huang
Summary: This retrospective study compares the durability of hepatitis B surface antigen (HBsAg) seroclearance induced by nucleoside analogs (NAs) or interferon (IFN). The study found significant differences in the one-year probabilities of HBsAg seroclearance between patients treated with NAs monotherapy and IFN monotherapy. IFN treatment induced HBsAg seroclearance has higher durability, and the presence of anti-HBs is significantly associated with a longer duration of functional cure.
Article
Biochemistry & Molecular Biology
Hongsheng Zhang, Lin Shao, Zhihao Lin, Quan-Xin Long, Huilong Yuan, Lujian Cai, Guangtong Jiang, Xiaoyi Guo, Renzhi Yang, Zepeng Zhang, Bingchang Zhang, Fan Liu, Zhiyong Li, Qilin Ma, Yun-Wu Zhang, Ai-Long Huang, Zhanxiang Wang, Yingjun Zhao, Huaxi Xu
Summary: APOE3 and APOE4 interact with the SARS-CoV-2 receptor ACE2, regulating viral entry and inflammatory response. APOE epsilon 4 carriers may be more susceptible to and develop severe COVID-19.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Chemistry, Multidisciplinary
Rui Yuan, Xiaopeng Bai, Xiaolin Hu, Hong Zhang, Changjun Hou, Quanxin Long, Yang Luo
Summary: This paper introduces a CATCH approach using CRISPR-Cas13a, which combines gene recognition with catalytic hairpin assembly amplification to accurately and impartially identify variants. In a pilot experiment involving 34 clinical samples, this approach achieved 100% accuracy.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Xin Xu, Sheng Nie, Yanqun Wang, Quanxin Long, Hong Zhu, Xiaoyong Zhang, Jian Sun, Qinglang Zeng, Jincun Zhao, Li Liu, Ling Li, Ailong Huang, Jinlin Hou, Fan Fan Hou
Summary: According to a study in Hubei, China, the dynamics of neutralizing antibody (NAbs) response to SARS-CoV-2 in COVID-19 patients showed that NAbs seroconversion occurred at around 5.5 days post onset, with a positivity rate of 52% within the first week, reaching 100% by the third week, and maintaining above 97% for up to 6 months. NAbs peaked in the fourth week and were positively associated with disease severity and age, while inversely associated with serum albumin levels. The half-life of NAbs was 61 days within the first two months, which then slowed to 104 days afterward.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Yong Lin, Jun Yuan, Quanxin Long, Jieli Hu, Haijun Deng, Zhenyu Zhao, Juan Chen, Mengji Lu, Ailong Huang
Summary: This study showed that patients with chronic HBV infection and SARS-CoV-2 co-infection are at higher risk of abnormal liver function tests. However, there were no significant differences in discharge rate or hospitalization duration between the two groups. Enhanced liver injury induced by the co-infection may be related to hepatocyte involvement and inflammatory response.
Article
Medicine, Research & Experimental
Jie Hu, Qingzhu Gao, Yang Yang, Jie Xia, Wanjun Zhang, Yao Chen, Zhi Zhou, Lei Chang, Yuan Hu, Hui Zhou, Li Liang, Xiaosong Li, Quanxin Long, Kai Wang, Ailong Huang, Ni Tang
Summary: Viral infection upregulates GLUT1 expression on hepatocytes, facilitating glucose uptake for UDP-GlcNAc synthesis via HBP and increasing protein O-GlcNAcylation to impact HBV replication. O-GlcNAcylation enhances host antiviral response by regulating SAMHD1.
