Article
Microbiology
Hao Yao, Guo Li, Xianglian Xiong, Fanxin Jin, Sirui Li, Xinyu Xie, Dan Zhong, Renling Zhang, Fanzeng Meng, Yuelan Yin, Xin'an Jiao
Summary: In this study, the researchers found that Gal-WTA plays a key role in modulating the autolysin protein LygA through direct interactions. These interactions are important for the colonization and infection of Listeria monocytogenes.
Review
Chemistry, Multidisciplinary
Nicholas Banahene, Herbert W. Kavunja, Benjamin M. Swarts
Summary: This article reviews the physiological functions of bacterial glycans and the development and applications of chemical reporters targeting bacterial glycans, including their use in diagnostics, therapeutics, and research.
Article
Microbiology
Cassandra Lenoir, Anais Pelletier, Sylvie Manuse, Hugo Millat, Adrien Ducret, Anne Galinier, Thierry Doan, Christophe Grangeasse
Summary: This study characterizes the regulatory function of the previously unknown protein Spr1400 in controlling the activity and localization of two important Penicillin-binding proteins (PBPs), PBP1a and PBP2b, in Streptococcus pneumoniae. The research utilizes a combination of techniques including genetic manipulation, protein biochemistry, and microscopy imaging to demonstrate that Spr1400 interacts with PBPs and influences their dynamics during the cell cycle. These findings highlight the importance of Spr1400 as a spatio-temporal regulator of PBP1a and PBP2b in pneumococcal morphogenesis.
Article
Immunology
Gavyn Chern Wei Bee, Kristen L. Lokken-Toyli, Stephen T. Yeung, Lucie Rodriguez, Tonia Zangari, Exene E. Anderson, Sourav Ghosh, Carla V. Rothlin, Petter Brodin, Kamal M. Khanna, Jeffrey N. Weiser
Summary: In early life, neonatal neutrophils show enhanced CD11b-dependent opsonophagocytosis, leading to improved protection against Streptococcus pneumoniae (Spn). The augmented function of neonatal neutrophils is mediated by higher CD11b surface expression and dampened efferocytosis, resulting in more CD11bhi aged neutrophils in peripheral blood. Experimentally impairing efferocytosis later in life increases CD11bhi neutrophils and improves protection against Spn.
Article
Multidisciplinary Sciences
Elisabeth Reithuber, Torbjorn Wixe, Kevin C. Ludwig, Anna Muller, Hanna Uvell, Fabian Grein, Anders E. G. Lindgren, Sandra Muschiol, Priyanka Nannapaneni, Anna Eriksson, Tanja Schneider, Staffan Normark, Birgitta Henriques-Normark, Fredrik Almqvist, Peter Mellroth
Summary: The compound class comprising a 1-amino substituted tetrahydrocarbazole (THCz) scaffold inhibits bacterial cell wall synthesis by targeting undecaprenyl pyrophosphate-containing lipid intermediates, displaying bactericidal activity against a broad range of gram-positive and selected gram-negative pathogens in low micromolar range. The ease of synthesizing and modifying THCz, compared to natural lipid II-binding antibiotics, makes it a promising scaffold for the development of cell wall-targeting antimicrobials.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Microbiology
Hisanori Domon, Satoru Hirayama, Toshihito Isono, Karin Sasagawa, Fumio Takizawa, Tomoki Maekawa, Katsunori Yanagihara, Yutaka Terao
Summary: The clinical efficacy of macrolides in pneumococcal disease is assumed to be linked to their ability to inhibit the release of pneumolysin. However, our previous study showed that oral administration of macrolides to mice infected with macrolide-resistant Streptococcus pneumoniae resulted in decreased levels of pneumolysin and proinflammatory cytokines without affecting bacterial load. This suggests that macrolides may have additional mechanisms for regulating proinflammatory activity.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Applied
Chengxin Li, Katarzyna A. Duda, Pernille L. Elverdal, Ian C. Skovsted, Christian Kjeldsen, David Teze, Jens O. Duus
Summary: The study characterized the previously unknown CPS structures of pneumococcal serotype 28F and 28A using NMR spectroscopy, chemical analysis, and AF4-MALS-dRI, revealing differences in sugar donor specificity of glycosyltransferases. It was also found that the OAc group affected the affinity for factor antiserum 23d, while P-2-Gro was crucial for cross-reactivity.
CARBOHYDRATE POLYMERS
(2021)
Article
Biochemistry & Molecular Biology
Cristina Gallego-Paramo, Noelia Hernandez-Ortiz, Pedro Garcia, Margarita Menendez
Summary: In this study, we investigated the tuning of natural lysin activity by acquiring enzymatic active domains (EADs) and cell wall binding domains (CWBDs). By combining EAD of Skl and cell wall choline-binding domain (CBD) of LytA, a chimeric lysin QSLA with superior antibacterial capacity was produced. The QSLA showed increased bacterial killing and extended substrate range compared to parental enzymes. This study provides a novel approach to design superior lysins and presents a promising therapeutic perspective.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Microbiology
Nicholas S. Briggs, Kevin E. Bruce, Souvik Naskar, Malcolm E. Winkler, David I. Roper
Summary: This review provides an overview of key protein complexes involved in cell division of Streptococcus pneumoniae, known as pneumococcus. It discusses the interaction of proteins in the divisome complex and the control mechanisms for cell division and cell wall synthesis required in S. pneumoniae, including the involvement of virulence factors and capsular polysaccharides.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biology
Liselot Dewachter, Julien Denereaz, Xue Liu, Vincent de Bakker, Charlotte Costa, Mara Baldry, Jean-Claude Sirard, Jan-Willem Veening
Summary: Research has uncovered that downregulation of the mevalonate pathway in Streptococcus pneumoniae leads to cell elongation, limiting the supply of cell wall precursors. Further investigation shows that this effect is due to a restriction in the production of undecaprenyl phosphate (Und-P), halting cell constriction. By combining clomiphene and amoxicillin, antimicrobial activity of amoxicillin is enhanced, resensitizing amoxicillin-resistant strains.
Article
Microbiology
Fernanda Raya Tonetti, Patricia Clua, Kohtaro Fukuyama, Guillermo Marcial, Jacinto Sacur, Gabriela Marranzino, Mikado Tomokiyo, Guadalupe Vizoso-Pinto, Apolinaria Garcia-Cancino, Shoichiro Kurata, Haruki Kitazawa, Julio Villena
Summary: This study evaluated the effects of different non-viable Lacticaseibacillus rhamnosus strains and their peptidoglycans on the respiratory immune response and primary/secondary respiratory infections. The results showed that NV1505 and NVIBL027 improved protection against viral and pneumococcal infections by modulating the respiratory immune response, while PG1505 demonstrated immunomodulatory activities distinct from other purified peptidoglycans.
Article
Microbiology
Federico Rosconi, Emily Rudmann, Jien Li, Defne Surujon, Jon Anthony, Matthew Frank, Dakota S. Jones, Charles Rock, Jason W. Rosch, Christopher D. Johnston, Tim van Opijnen
Summary: Pan-genome analysis of clinical pneumococcal strains identified categories of essential genes and demonstrated that gene essentiality can be influenced by genetic background and specific genetic changes. The study revealed that gene essentiality can be affected by various factors and some genes remain crucial for survival with inactivation leading to severe fitness costs.
NATURE MICROBIOLOGY
(2022)
Article
Biology
Josue Flores-Kim, Genevieve S. Dobihal, Thomas G. Bernhardt, David Z. Rudner
Summary: A new factor called WhyD has been discovered to control the level of WTAs in Streptococcus pneumoniae cells, preventing the misactivation and lysis of the autolysin LytA. WhyD restricts the content of WTAs to areas adjacent to active peptidoglycan synthesis. The WTA tailoring activity of WhyD during exponential growth is crucial for proper cell elongation and preventing autolysis by LytA.
Article
Immunology
Eileen M. Dunne, Yinglei Hua, Rasheed Salaudeen, Ilias Hossain, Malick Ndiaye, Belinda D. Ortika, E. Kim Mulholland, Jason Hinds, Sam Manna, Grant A. Mackenzie, Catherine Satzke
Summary: We investigated the pathogenesis of pneumococcal pneumonia using clinical samples. Results demonstrated that pneumococci in the lung originated from the nasopharynx and suggested that changes in pneumococcal gene expression in the lung are a feature of pneumococcal pneumonia.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Jessica A. Wyllie, Mirrin V. McKay, Andrew S. Barrow, Tatiana P. Soares da Costa
Summary: This review explores the enzymes involved in the biosynthesis of UDP-N-acetylglucosamine, an essential component in bacterial peptidoglycan, and compares the differences and similarities between bacterial and eukaryotic enzymes. Additionally, it summarizes the recent advances in developing inhibitors that target bacterial enzymes.
Review
Physiology
Sara Nathan, Sandra B. Gabelli, Jesse B. Yoder, Lakshmi Srinivasan, Richard W. Aldrich, Gordon F. Tomaselli, Manu Ben-Johny, L. Mario Amzel
Summary: This review focuses on the structural insights into the cytoplasmic C-terminal regulation of Na(V)1.4 and Na(V)1.5, with special attention to Ca2+ sensing by calmodulin, implications for disease, and putative channel dimerization. The determination of eukaryotic Na(V)s structures by cryo-electron microscopy has provided new perspectives on the study of the channels, highlighting the complementary nature of techniques and the intricate cellular mechanisms that modulate these channels.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Antonieta L. Salguero, Maggie Chen, Aaron T. Balana, Nam Chu, Hanjie Jiang, Brad A. Palanski, Hwan Bae, Katharine M. Wright, Sara Nathan, Heng Zhu, Sandra B. Gabelli, Matthew R. Pratt, Philip A. Cole
Summary: This study investigates the regulatory effects of phosphorylation of Tyr474 and O-GlcNAcylation of Ser473 on Akt, finding that both modifications can increase Akt's kinase activity toward substrates. Kinase assays using protein microarrays showed high similarity in the protein substrates phosphorylated by phosphoSer473 Akt and O-GlcNAcSer473 Akt. Two Akt substrates, PPM1H and NEDD4L, were validated in further solution-phase assays and cell transfection experiments.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lakshmi Srinivasan, Vanina Alzogaray, Dakshnamurthy Selvakumar, Sara Nathan, Jesse B. Yoder, Katharine M. Wright, Sebastian Klinke, Justin N. Nwafor, Maria S. Labanda, Fernando A. Goldbaum, Arne Schon, Ernesto Freire, Gordon F. Tomaselli, L. Mario Amzel, Manu Ben-Johny, Sandra B. Gabelli
Summary: In this study, high-affinity anti-Na-V nanobodies (Nbs) Nb17 and Nb82 were generated using phage display technology. These Nbs specifically recognize the Na(V)1.4 and Na(V)1.5 channel isoforms. The results show that Nb17 and Nb82 bind to the CTNa(V)1.4 and CTNa(V)1.5 with high affinity and can detect Na(V)1.4 and Na(V)1.5 channels in mammalian cells and tissues.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Thu Nguyen, Kim L. Phan, Dima Kozakov, Sandra B. Gabelli, Dale F. Kreitler, Lawrence C. Andrews, Jean Jakoncic, Robert M. Sweet, Alexei S. Soares, Herbert J. Bernstein
Summary: Small but measurable differences in diffraction data from different crystals of the same protein may reflect structural differences and reveal the natural dynamics of the molecule. Sorting mixed-state data into relevant clusters is crucial for extracting information about protein dynamics. The study presents a simple multi-factor clustering approach using independent observables to classify data sets and assigns them to the correct conformational space location. Results from applying this approach to chymotrypsinogen crystals show an arc-like distribution along the reaction trajectory to chymotrypsin.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Cell Biology
Dimitrios Tsitsipatis, Jennifer L. Martindale, Ceereena Ubaida-Mohien, Alexey Lyashkov, Hagai Yanai, Amogh Kashyap, Chang Hoon Shin, Allison B. Herman, Eunbyul Ji, Jen-Hao Yang, Rachel Munk, Christopher Dunn, Yevgeniya Lukyanenko, Xiaoling Yang, Chee W. Chia, Ajoy C. Karikkineth, Linda Zukley, Jarod D'Agostino, Mary Kaileh, Chang-Yi Cui, Isabel Beerman, Luigi Ferrucci, Myriam Gorospe
Summary: This study analyzed proteins from primary skin fibroblasts of 82 healthy individuals to identify key pathways associated with skin fibroblast aging, including autophagy, ROS scavenging, ribosome biogenesis, DNA replication, and repair. The study establishes a framework of the global proteome governing skin fibroblast aging and points to potential biomarkers and therapeutic targets for future research.
Article
Biochemistry & Molecular Biology
Hanjie Jiang, Claire Y. Chiang, Zan Chen, Sara Nathan, Gabriel D'Agostino, Joao A. Paulo, Guang Song, Heng Zhu, Sandra B. Gabelli, Philip A. Cole
Summary: In this study, potential substrates of WWP2 were identified using protein microarray technology and an activated enzyme phosphomimetic mutant WWP2(Y369E). Three autophagy receptors were found among the identified substrates and their lysine ubiquitination sites were mapped. Functional assays confirmed the validation of these substrates, and WWP2 was found to play a positive role in mitophagy regulation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Srona Sengupta, Nathan L. Board, Fengting Wu, Milica Moskovljevic, Jacqueline Douglass, Josephine Zhang, Bruce R. Reinhold, Jonathan Duke-Cohan, Jeanna Yu, Madison C. Reed, Yasmine Tabdili, Aitana Azurmendi, Emily J. Fray, Hao Zhang, Emily Han-Chung Hsiue, Katharine Jenike, Ya-Chi Ho, Sandra B. Gabelli, Kenneth W. Kinzler, Bert Vogelstein, Shibin Zhou, Janet D. Siliciano, Scheherazade Sadegh-Nasseri, Ellis L.Reinherz, Robert F. Siliciano
Summary: HIV-1 infection is incurable due to the persistence of the virus in a latent reservoir of resting memory CD4(+) T cells. The lack of effective latency-reversing agents and kill strategies has hindered the success of shock-and-kill approaches. This study develops T cell receptor-mimic antibodies that promote killing of infected cells and lays the foundation for a novel therapeutic killing strategy toward elimination of the HIV-1 reservoir.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Hagai Yanai, Christopher Dunn, Bongsoo Park, Christopher Coletta, Ross A. McDevitt, Taylor McNeely, Michael Leone, Robert P. Wersto, Kathy A. Perdue, Isabel Beerman
Summary: Although rats are more physiologically similar to humans, the age-associated changes in their hematopoietic system have not been extensively explored. This study examined peripheral blood of male F344 rats and found significant age-associated changes, with CD25(+) CD4(+) population frequency as a strong predictor of healthy aging. Blood parameters and DNA methylation alterations defined key points in the aging process, supporting a non-linear aging process. These findings are important for aging interventions.
Correction
Immunology
Roshni Roy, Senthilkumar Ramamoorthy, Benjamin D. Shapiro, Mary Kaileh, Dena Hernandez, Dimitra Sarantopoulou, Sampath Arepalli, So Ren Boller, Amit Singh, Arsun Bektas, Jaekwan Kim, Ann Zenobia Moore, Toshiko Tanaka, Julia McKelvey, Linda Zukley, Cuong Nguyen, Tonya Wallace, Christopher Dunn, Robert Wersto, William Wood, Yulan Piao, Kevin G. Becker, Christopher Coletta, Supriyo De, Jyoti Misra Sen, Alexis Battle, Nan-ping Weng, Rudolf Grosschedl, Luigi Ferrucci, Ranjan Sen
Article
Multidisciplinary Sciences
Jian Lu, Raheel Ahmad, Thomas Nguyen, Jeffrey Cifello, Humza Hemani, Jiangyuan Li, Jinguo Chen, Siyi Li, Jing Wang, Achouak Achour, Joseph Chen, Meagan Colie, Ana Lustig, Christopher Dunn, Linda Zukley, Chee W. Chia, Irina Burd, Jun Zhu, Luigi Ferrucci, Nan-Ping Weng
Summary: The decline of CD8(+) T cell functions with aging is a significant health issue, and this study uses single-cell RNA sequencing and machine learning to understand the mechanisms and predict the age of individual cells. This research has important implications for predicting functional outcomes in vaccination or infection.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Linda K. Krasniewski, Papiya Chakraborty, Chang-Yi Cui, Krystyna Mazan-Mamczarz, Christopher Dunn, Yulan Piao, Jinshui Fan, Changyou Shi, Tonya Wallace, Cuong Nguyen, Isabelle A. Rathbun, Rachel Munk, Dimitrios Tsitsipatis, Supriyo De, Payel Sen, Luigi Ferrucci, Myriam Gorospe
Summary: By single-cell transcriptomic analysis, researchers identified 11 macrophage clusters in skeletal muscle, with four subgroups identified by membrane markers. Macrophages in old skeletal muscle showed increased proinflammatory and senescence-related traits.
Article
Geriatrics & Gerontology
Jian Lu, Guobing Chen, Arina Sorokina, Thomas Nguyen, Tonya Wallace, Cuong Nguyen, Christopher Dunn, Stephanie Wang, Samantha Ellis, Guixin Shi, Julia McKelvey, Alexei Sharov, Yu-Tsueng Liu, Jonathan Schneck, Nan-ping Weng
Summary: In young and middle-aged healthy adults, CMV infection causes mild expansion of CMV-specific CD8(+) T cells, decreased CD70 expression and signaling, and reduced proliferation of CMV-specific CD8(+) T-CM cells. These effects are age-independent and specific to CMV infection.
Article
Multidisciplinary Sciences
Fu-Lien Hsieh, Tao-Hsin Chang, Sandra B. Gabelli, Jeremy Nathans
Summary: Diverse extracellular proteins, including adenomatosis polyposis coli down-regulated 1 (APCDD1), are negative regulators of WNT signaling. The structure of APCDD1's extracellular domain consists of two closely apposed 3-barrel domains (ABD1 and ABD2), with ABD2 having a hydrophobic pocket that can bind lipid. The extracellular domain of APCDD1 can also bind to WNT7A through covalently attached palmitoleate, an essential modification for WNT signaling. This study suggests that APCDD1 functions as a negative feedback regulator by sequestering WNT ligands on the cell surface.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B. Zorov, H. Bradley Nuss, Yael Yaniv, Kenneth W. Fishbein, Rafael de Cabo, Lluis Montoliu, Sandra B. Gabelli, Miguel A. Aon, Sonia Cortassa, Steven J. Sollott
Summary: ATP synthase can utilize both Delta psi(m)-driven H+- and K+-transport to synthesize ATP under physiological conditions. The presence of K+ increases ATP synthesis rate in isolated mitochondria while also increasing oxygen consumption rate. The data obtained from purified F1Fo single molecule experiments are consistent with the functional data observed in intact mitochondria.
Article
Cell Biology
Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B. Zorov, H. Bradley Nuss, Yael Yaniv, Kenneth W. Fishbein, Rafael de Cabo, Lluis Montoliu, Sandra B. Gabelli, Miguel A. Aon, Sonia Cortassa, Steven J. Sollott
Summary: ATP synthase serves as the primary way for K+ to enter mitochondria, and its activity can be upregulated by endogenous survival-related proteins via IF1. The interaction between IF1 and Bcl-xL or Mcl-1 enhances ATP synthase's efficiency and limits ischemia-reperfusion injury.
