Review
Microbiology
Frederic De Meyer, Aurelien Carlier
Summary: Serine protease inhibitors are a diverse group of proteins involved in critical biological pathways. Most inhibitors target specific protease substrates while ecotin is able to inhibit a wide range of serine proteases with different specificities. Its unique flexibility upon binding to targets is driven by special structural features. This review aims to update our understanding of the biological importance, role in host-microbe interactions, and evolutionary relationship of ecotin orthologs across different species.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Cell Biology
Wen Zhang, Kai Liu, Guang-Ming Ren, Yu Wang, Ting Wang, Xian Liu, Dong-Xu Li, Yang Xiao, Xu Chen, Ya-Ting Li, Yi-Qun Zhan, Shen-Si Xiang, Hui Chen, Hui-Ying Gao, Ke Zhao, Miao Yu, Chang-Hui Ge, Chang-Yan Li, Zhi-Qiang Ge, Xiao-Ming Yang, Rong-Hua Yin
Summary: This study investigated the pathophysiological role of BRISC in acute liver failure. The expression of BRISC components was found to increase in kupffer cells (KCs) upon LPS treatment, and the deficiency of BRISC significantly attenuated liver damage and inflammation response. The study demonstrated that BRISC is involved in NF-kappa B-mediated proinflammatory cytokines production in LPS-treated KCs. This research opens the possibility for the development of new strategies to inhibit KCs-driven inflammation in liver diseases.
CELL DEATH & DISEASE
(2023)
Review
Medicine, Research & Experimental
Xiao Li, Xinyuan Sun, Xuemin Guo, Xueren Li, Shouchun Peng, Xin Mu
Summary: Nucleic acid-mediated interferon signaling plays a pivotal role in defense against microorganisms, especially during viral infection. This article discusses the receptors involved in sensing nucleic acid molecules, their structures and functions, and the importance of their proper functioning in cell homeostasis and response to pathogen invasion. It also explores the impact of manipulating these receptors on defense mechanisms and presents the discovery of chemicals that can modulate their signaling activities.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Xin Zhang, Xiulin Lin, Hui Luo, Yuanxing Zhi, Xin Yi, Xiaoyan Wu, Wendi Duan, Ying Cao, Jianxin Pang, Shuwen Liu, Pingzheng Zhou
Summary: Potassium efflux mediated by the Kv1.3 channel plays a critical role in TLR3/4 activation, and pharmacological inhibition of Kv1.3 may be beneficial for treating autoimmune diseases and bacterial infections.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Anette Christ, Pieter G. Goossens, Erwin Wijnands, Han Jin, Bart Legein, Tammy Oth, Aaron Isaacs, Monika Stoll, Joris Vanderlocht, Esther Lutgens, Mat J. A. P. Daemen, Martin Zenke, Erik A. L. Biessen
Summary: Hyperlipidemia significantly affects the activation and immune response of pDCs, particularly in response to pathogen-derived signals.
Article
Biochemistry & Molecular Biology
Tanaya Bagga, S. N. Loh, J. Sivaraman, Srihari Shankar
Summary: This study reports the crystal structure of human neutrophil elastase (hNE) in complex with a peptide inhibitor derived from ecotin (ET). The study found that short linear peptides and circular amide backbone-linked peptides had inefficient inhibition of hNE. Structural insights point to a preferred amino acid sequence and the potential benefits of a scaffold for optimal binding and function of the peptide inhibitor.
Article
Oncology
Natalia Teresa Jarzebska, Marina Tusup, Julia Frei, Tobias Weiss, Tim Holzinger, Mark Mellett, Mustafa Diken, Simon Bredl, Michael Weller, Roberto F. Speck, Thomas M. Kundig, Ugur Sahin, Steve Pascolo
Summary: Nanoparticles of different sizes engage TLRs and activate innate immune responses both in vitro and in vivo. The schedule of injections affects the magnitude of the immune response. In a tumor model, nanoparticles can clear lung metastasis but have no effect on subcutaneous tumors. By incorporating chemotherapeutic base analogues, nanoparticles can effectively control various types of tumors.
Article
Biochemistry & Molecular Biology
Yanchao Gu, Jingjing Tang, Fuhua Zhang, Yichen Qu, Min Zhao, Mengyuan Li, Zhen Xie, Xiao Wang, Li Song, Zhengfan Jiang, Yao Wang, Xihui Shen, Lei Xu
Summary: Divalent metal ions such as Mn2+ and Zn2+ have immunostimulatory effects and can enhance the expression of genes involved in innate immune responses induced by lipopolysaccharide. The enhancement of gene expression by Mn2+ is dose-dependent and partially relies on the cGAS-STING pathway independent of TLR4. Mn2+ has the potential to be a therapeutic target for preventing excessive immune responses.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Si Lhyam Myint, Nikola Zlatkov, Kyaw Min Aung, Eric Toh, Annika Sjostrom, Aftab Nadeem, Marylise Duperthuy, Bernt Eric Uhlin, Sun Nyunt Wai
Summary: This study identified two proteins in E. coli, Ecotin and LamB, that influenced E. coli susceptibility to T6SS-mediated killing by V. cholerae. Manipulating the expression of these proteins could potentially modulate inter-bacterial competition in vivo, such as in the gastrointestinal microbiome.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Reproductive Biology
Xu Han, Siyuan Wang, Ying Ren, Tao Lin, Leying Zhang, Ling Yang
Summary: This study investigates the changes in plasma protein levels during early pregnancy in cattle and develops a colloidal gold immunochromatographic test strip for early pregnancy diagnosis. The results suggest that the changes in plasma protein levels may be related to maternal immune modulation, and complement component 1q (C1q) can be used as an ideal marker for early pregnancy diagnosis in cows. However, further studies are needed to improve the accuracy of the test strip.
Article
Immunology
Natalya Odoardi, Olena Kourko, Carlene Petes, Sameh Basta, Katrina Gee
Summary: Regulation of proinflammatory cytokine expression is crucial in ssRNA virus infections. IL-27 has a modulatory role on TLR7 and TLR8 responses, enhancing TLR7 expression and TLR8-mediated cytokine secretion. Additionally, TLR7 agonist can inhibit cytokine and chemokine production induced by a TLR8 agonist.
JOURNAL OF INNATE IMMUNITY
(2021)
Article
Food Science & Technology
Misa Nakasuji-Togi, Sumihito Togi, Keita Saeki, Yasuhiko Kojima, Keiko Ozato
Summary: The study found that the internatural (INT) mixture can induce type I interferons (IFNs) in murine bone marrow-derived macrophages (BMDMs) to enhance the body's immunity. This induction is mediated by the Toll-like receptor 4 (TLR4) pathway. The supernatants from INT-treated cells also displayed antiviral activity.
FOOD & NUTRITION RESEARCH
(2022)
Review
Medicine, General & Internal
Wen-Ming Wang, Feng Li, Hong-Zhong Jin
Summary: Psoriasis is a chronic inflammatory disease where TLRs, IRFs, and type I IFNs play important roles in its pathogenesis. These factors interact with each other, regulating the development of psoriasis.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2021)
Article
Oncology
Donghwan Jeon, Douglas G. McNeel
Summary: The presence of specific Toll-like receptor (TLR) agonists can attenuate the expression of PD-1 in activated CD8(+) T-cells, leading to an improvement in anti-tumor activity. Different TLR agonists have distinct effects on the gene expression profiles of T-cells, especially in combination with TLR1/2, TLR3, and TLR9. Combining TLR3 and TLR9 agonists for tumor vaccination can effectively suppress tumor growth.
Article
Biochemistry & Molecular Biology
Bo-Ram Jo, Hyun-Soo Kim, Jeong-Won Ahn, Eui-Young Jeoung, Su-Kil Jang, Yeong-Min Yoo, Seong-Soo Joo
Summary: Pathogenesis-related (PR) proteins in plants play a crucial role in plant defense against microbial attacks. In this study, a novel PR-1-like protein (OPRP) was identified and its pharmacologic relevance and cell signaling in mammalian cells were examined. The purified full-length OPRP protein increased the expression levels of genes involved in the immune response, while small peptides designed from OPRP upregulated antiviral genes in mouse splenocytes and human epithelial cells. OPRP and its small peptides activated specific signaling pathways and inhibited viral entry into host cells.
Article
Infectious Diseases
Carolina Torturella Rath, Laila Castro Schnellrath, Clarissa R. Damaso, Luciana Barros de Arruda, Pedro Fernando da Costa Vasconcelos, Claudia Gomes, Marcia Dalastra Laurenti, Teresa Cristina Calegari Silva, Aislan de Carvalho Vivarini, Nicolas Fasel, Renata Meirelles Santos Pereira, Ulisses Gazos Lopes
PLOS NEGLECTED TROPICAL DISEASES
(2019)
Article
Microbiology
Andreas Damianou, Rebecca J. Burge, Carolina M. C. Catta-Preta, Vincent Geoghegan, Y. Romina Nievas, Katherine Newling, Elaine Brown, Richard Burchmore, Boris Rodenko, Jeremy C. Mottram
Article
Microbiology
Manuel Saldivia, Eric Fang, Xiaolei Ma, Elmarie Myburgh, Juliana B. T. Carnielli, Christopher Bower-Lepts, Elaine Brown, Ryan Ritchie, Suresh B. Lakshminarayana, Yen-Liang Chen, Debjani Patra, Elizabeth Ornelas, Hazel X. Y. Koh, Sarah L. Williams, Frantisek Supek, Daniel Paape, Richard McCulloch, Marcel Kaiser, Michael P. Barrett, Jan Jiricek, Thierry T. Diagana, Jeremy C. Mottram, Srinivasa P. S. Rao
NATURE MICROBIOLOGY
(2020)
Article
Microbiology
Clare Halliday, Ryuji Yanase, Carolina Moura Costa Catta-Preta, Flavia Moreira-Leite, Jitka Myskova, Katerina Pruzinova, Petr Volf, Jeremy C. Mottram, Jack D. Sunter
Article
Genetics & Heredity
John W. Davey, Carolina M. C. Catta-Preta, Sally James, Sarah Forrester, Maria Cristina M. Motta, Peter D. Ashton, Jeremy C. Mottram
Summary: The nuclear genome assembly of Angomonas deanei reveals 29 complete or close-to-complete chromosomes with unique features like supernumerary chromosome, a 340-kb inversion in one chromosome, and a translocation between two chromosomes. The updated annotation includes 10,365 protein-coding genes, 59 transfer RNAs, 26 ribosomal RNAs, and 62 noncoding RNAs.
G3-GENES GENOMES GENETICS
(2021)
Article
Microbiology
Asma Belbelazi, Rachel Neish, Martin Carr, Jeremy C. Mottram, Michael L. Ginger
Summary: In eukaryotes, heme attachment to mitochondrial cytochromes c is catalyzed by two different systems, with one being inherited from the alphaproteobacterial progenitor and the other being a eukaryotic innovation. Unique to euglenozoan protists is the attachment of heme to cytochromes c by a single thioether linkage, with the mechanism remaining unknown. The discovery of kinetoplastid cytochrome c synthetase (KCCS) provides a novel resource for studying eukaryotic cytochrome c maturation and may have wider implications in the context of human genetic diseases.
Article
Microbiology
Antonio Luis de O. A. Petersen, Benjamin Cull, Beatriz R. S. Dias, Luana C. Palma, Yasmin da S. Luz, Juliana P. B. de Menezes, Jeremy C. Mottram, Patricia S. T. Veras
Summary: The Hsp90 inhibitor 17-AAG was shown to cause abnormal activation of the autophagic pathway, leading to the formation of immature autophagosomes and subsequent parasite death. This study provides evidence of the role of autophagy in 17-AAG-induced cell death, supporting the potential of Hsp90 as a drug target for parasitic diseases.
Article
Microbiology
Sarah Forrester, Amy Goundry, Bruna Torres Dias, Thyago Leal-Calvo, Milton Ozorio Moraes, Paul M. Kaye, Jeremy C. Mottram, Ana Paula C. A. Lima
Summary: This study used dual RNA-seq to investigate the transcriptional response of host and parasite in a mouse model of visceral leishmaniasis caused by Leishmania infantum and Leishmania donovani. The results showed that the host response was broadly similar in both infections, with around 10% of host differentially expressed genes varying between the two parasite species.
MICROBIOLOGY SPECTRUM
(2022)
Review
Parasitology
Mathieu Cayla, Y. Romina Nievas, Keith R. Matthews, Jeremy C. Mottram
Summary: Trypanosomatid parasitic protozoa have evolved unique mechanisms, such as protein kinases, to regulate their complex life cycles and adapt to different hosts, distinguishing them from other eukaryotes.
TRENDS IN PARASITOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tatiana F. R. Costa, Amy Goundry, Alexandre Morrot, Dennis J. Grab, Jeremy C. Mottram, Ana Paula C. A. Lima
Summary: This study reveals the mechanism of Trypanosoma brucei rhodesiense penetration through the blood-brain barrier and causing sleeping sickness. The Cathepsin L-like cysteine peptidase and its endogenous inhibitor ICP play important roles in the infection process and regulate inflammatory responses. The results suggest that ICP helps to downregulate inflammatory responses and control the infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Vincent Geoghegan, Juliana B. T. Carnielli, Nathaniel G. Jones, Manuel Saldivia, Sergios Antoniou, Charlotte Hughes, Rachel Neish, Adam Dowle, Jeremy C. Mottram
Summary: This study developed a new proximity biotinylation method to investigate the kinetochore of Leishmania parasites. By using this method, researchers identified novel kinetochore proteins and revealed the dynamic changes of the kinetochore during the parasite cell cycle. Additionally, the study uncovered the mechanism of action of a kinase inhibitor on the kinetochore, providing insights for finding new drug targets.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Medicinal
Catherine N. Russell, Jennifer L. Carter, Juliet M. Borgia, Jacob Bush, Felix Calderon, Raquel Gabarro, Stuart J. Conway, Jeremy C. Mottram, Anthony J. Wilkinson, Nathaniel G. Jones
Summary: Leishmaniases are neglected tropical diseases caused by Leishmania parasites, and current treatments are limited. This study identifies bromodomains as a potential target for antileishmanial drug discovery and demonstrates that BDF5 bromodomains bind to human bromodomain inhibitors and exhibit activity against Leishmania promastigotes.
ACS INFECTIOUS DISEASES
(2023)
Article
Microbiology
Rebecca J. Burge, Andreas Damianou, Anthony J. Wilkinson, Boris Rodenko, Jeremy C. Mottram
Review
Infectious Diseases
Emily A. Dickie, Federica Giordani, Matthew K. Gould, Pascal Maeser, Christian Burri, Jeremy C. Mottram, Srinivasa P. S. Rao, Michael P. Barrett
TROPICAL MEDICINE AND INFECTIOUS DISEASE
(2020)
Article
Infectious Diseases
Srinivasa P. S. Rao, Suresh B. Lakshminarayana, Jan Jiricek, Marcel Kaiser, Ryan Ritchie, Elmarie Myburgh, Frantisek Supek, Tove Tuntland, Advait Nagle, Valentina Molteni, Pascal Maeser, Jeremy C. Mottram, Michael P. Barrett, Thierry T. Diagana
TROPICAL MEDICINE AND INFECTIOUS DISEASE
(2020)