Article
Multidisciplinary Sciences
Rei Nakamoto, Jeric Mun Chung Kwan, Jasmine Fei Li Chin, Hui Ting Ong, Josue Flores-Kim, Caroline Midonet, Michael S. VanNieuwenhze, Xue Li Guan, Lok-To Sham
Summary: Many pathogenic bacteria rely on a layer of capsular polysaccharide (CPS) for virulence, with the bacterial tyrosine kinase (BY-kinase) playing a crucial role in regulating capsule synthesis. The interaction between BY-kinase CpsCD and other proteins influences CPS polymer length and peptidoglycan synthesis in Streptococcus pneumoniae. Autophosphorylation of BY-kinases fine-tunes the activity of CpsC, providing spatiotemporal coordination between CPS and PG synthesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Philip H. C. Kremer, Bart Ferwerda, Hester J. Bootsma, Nienke Y. Rots, Alienke J. Wijmenga-Monsuur, Elisabeth A. M. Sanders, Krzysztof Trzcinski, Anne L. Wyllie, Paul Turner, Arie van der Ende, Matthijs C. Brouwer, Stephen D. Bentley, Diederik van de Beek, John A. Lees
Summary: This study identified genetic variations in pneumococcal carriage that differ between infants and adults. Serotypes and genetic background were found to explain a proportion of the heritability in carriage. The findings support the proposal for adaptive vaccination strategies targeting dominant circulating serotypes and tailored to the composition of the pathogen populations.
Article
Chemistry, Analytical
Raine Garrido, Barbara Baro, Jean Pierre Soubal, Darielys Santana
Summary: This study presents an improved quantitative P-31-NMR methodology for the quantification of C-polysaccharide in capsular polysaccharide preparations, allowing discrimination between phosphocholine residues linked in different positions. The method was successfully applied to samples of vaccine serotypes, showing good quantification performance with a signal/noise ratio of 16:1. Repeatability and intermediate precision evaluation demonstrated the method's stability, while also providing information on the structural identity of phosphate contained in capsular polysaccharides and C-polysaccharide species.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Microbiology
Jinghui Zhang, Weijie Ye, Kaifeng Wu, Shengnan Xiao, Yuqiang Zheng, Zhaoche Shu, Yibing Yin, Xuemei Zhang
Summary: Streptococcus pneumoniae can alter its cell surface phenotype in response to the host environment; FabT indirectly regulates capsular polysaccharide, while PsrA is responsible for phase variation; Upregulation of PsrA correlates with more T phase variants, while inactivation of PsrA leads to O variants.
Article
Microbiology
Mary A. Carr, Dennis Marcelo, K. Michael Lovell, Angela H. Benton, Nathan A. Tullos, Erin W. Norcross, Brandon Myers, Marcus K. Robbins, Hayley Craddieth, Mary E. Marquart
Summary: The bacterial capsule in Streptococcus pneumoniae keratitis affects its pathogenicity, and the absence of the capsule impacts inflammation.
Article
Multidisciplinary Sciences
Ye -Yu Chun, Kai Sen Tan, Lisa Yu, Michelle Pang, Ming Hui Millie Wong, Rei Nakamoto, Wan-Zhen Chua, Amanda Huee-Ping Wong, Zhe Zhang Ryan Lew, Hsiao Hui Ong, Vincent T. Chow, Thai Tran, De Yun Wang, Lok-To Sham
Summary: The composition and structure of surface polysaccharides of Streptococcus pneumoniae affect their binding to epithelial cells and stimulate the production of immune-related proteins in nasal epithelial cells. The glycomotifs of surface polysaccharides are likely to play a crucial role in colonization and survival in the human airway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Dominic Dolbec, Melanie Lehoux, Masatoshi Okura, Daisuke Takamatsu, Marcelo Gottschalk, Mariela Segura
Summary: In this study, we compared the protective properties of different serotypes of Streptococcus suis using serotype-switched mutants in a mouse infection model. The structure of the capsular polysaccharide (CPS) influenced bacterial survival, antibody binding, and antibody-mediated bacterial killing. CPS of serotypes 3, 4, and 14 allowed more antibody binding and bacterial elimination compared to serotypes 2, 7, and 9. These findings suggest that the varying CPS structures of S. suis provide different levels of protection by affecting antigen availability and elimination by the host immune system.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chengxin Li, Kirstine B. Andersen, Pernille L. Elverdal, Ian C. Skovsted, Jens O. Duus, Christian Kjeldsen
Summary: After investigating the capsular polysaccharide of Streptococcus pneumoniae serotype 15F, it was found to have a different phosphorylation substituent and the structure was determined. The locations of previously unassigned O-acetyl groups were identified and full NMR assignments were carried out for 15F and 15A CPS. Lastly, a biosynthetic analysis was performed on serotypes 15F and 15A, leading to a prediction for the structure of the newly discovered serotype 15D.
CARBOHYDRATE RESEARCH
(2021)
Article
Microbiology
Tomoko Sumitomo, Masanobu Nakata, Satoshi Nagase, Yuki Takahara, Mariko Honda-Ogawa, Yasushi Mori, Yukako Akamatsu, Masaya Yamaguchi, Shigefumi Okamoto, Shigetada Kawabata
Summary: Influenza A virus infection increases susceptibility to secondary bacterial pneumonia, with GP96 on infected cell surfaces mediating interactions with Streptococcus pneumoniae, leading to increased bacterial adherence and translocation. Inhibition of GP96 enhances pneumococcal clearance and reduces lung pathology in infected mice, suggesting a potential therapeutic target for inhibiting bacterial colonization in an IAV-infected respiratory tract.
Article
Microbiology
Wan-Zhen Chua, Matthias Maiwald, Kean Lee Chew, Raymond Tzer-Pin Lin, Sanduo Zheng, Lok-To Sham
Summary: MOP family transporters, responsible for transporting lipid-linked precursors to support glycoconjugate synthesis, were systematically tested for their ability to translocate noncognate cargo. Subtle changes in the transporter structure can accommodate different cargoes and potentially expand substrate selectivity. By evaluating the interchangeability of these transporters, important residues for substrate specificity and function were identified, with implications for glycoengineering, vaccine development, and antimicrobial discovery.
Review
Immunology
Caroline M. Weight, Simon P. Jochems, Hugh Adler, Daniela M. Ferreira, Jeremy S. Brown, Robert S. Heyderman
Summary: Nasopharyngeal carriage of Streptococcus pneumoniae is common in humans, especially in older individuals. Pneumococcal conjugate vaccines have had some success in protecting young children and indirectly older people through herd immunity, but serotype replacement is still a concern. Older individuals often experience chronic inflammation, known as 'Inflammageing', which may increase mortality risk and affect the outcome of pneumococcal infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Natalha T. Waz, Sheila Oliveira, Raquel Girardello, Nilton Lincopan, Giovana Barazzone, Thais Parisotto, Anders P. Hakansson, Thiago Rojas Converso, Michelle Darrieux
Summary: Streptococcus pneumoniae is a globally prevalent pathogen with a highly immunogenic polysaccharide capsule. Indolicidin, an antimicrobial peptide, has bactericidal effects against this pathogen, but the capsule variability may influence its susceptibility.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Immunology
Kat Franklin, Brenda Kwambana-Adams, Fernanda C. Lessa, Heidi M. Soeters, Laura Cooper, Matthew E. Coldiron, Jason Mwenda, Martin Antonio, Tomoka Nakamura, Ryan Novak, Adam L. Cohen
Summary: The study reviewed and analyzed 10 potential pneumococcal meningitis outbreaks in Africa between 2000 and 2018. These outbreaks showed lower peak attack rates than meningococcal meningitis outbreaks and were characterized by a predominance of serotype 1. Patients with pneumococcal meningitis tended to be older and had a higher case fatality rate compared to meningococcal meningitis cases. Improved laboratory testing for S. pneumoniae is essential for early outbreak identification.
JOURNAL OF INFECTIOUS DISEASES
(2021)
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
Jeremy A. Duke, Amy Paschall, John Glushka, Andrew Lees, Kelley W. Moremen, Fikri Y. Avci
Summary: This study explores the use of galactose oxidase (GOase) in a chemoenzymatic approach to generate a conjugate vaccine against Streptococcus pneumoniae. The results show that GOase can generate aldehyde motifs on the capsular polysaccharides of S. pneumoniae in a site-specific and reversible manner. The conjugate vaccine synthesized using GOase demonstrates improved humoral response and functional protection compared to the traditional sodium periodate oxidation method.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Infectious Diseases
Atsushi Hirayama, Jun Masui, Ayumi Murayama, Satomi Fujita, Jun Okamoto, Jun Tanaka, Takanori Hirayama, Toshitake Ohara, Emma Nakagawa Hoffmann, Jingwen Zhang, Haruna Kawachi, Hideo Okuno, Shigeto Hamaguchi, Kazunori Tomono, Rumiko Asada
Summary: This study explored the clinical course of COVID-19 patients receiving invasive mechanical ventilation in Japan, with a 30-day mortality rate of 24.0%. It was found that patients were intubated within 14 days of clinical onset in the majority of cases, and age of 65 or older and male gender were significantly associated with higher 30-day mortality rate.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Chemistry, Analytical
Wilfred Villariza Espulgar, Masato Saito, Kazuya Takahashi, Sakiko Ushiro, Norihisa Yamamoto, Yukihiro Akeda, Shigeto Hamaguchi, Kazunori Tomono, Eiichi Tamiya
Summary: The improved COP microfluidic chip and PCR amplification system for the rapid detection of CRE is controlled by 7G and able to detect bla(IMP-6) from patient samples with high certainty within 15 minutes. It can also detect other target genes, such as bla(NDM-1) and bla(OXA-23), showing potential in aiding global healthcare with antibiotic resistance issues.
Article
Microbiology
Tonia Zangari, Mila B. Ortigoza, Kristen L. Lokken-Toyli, Jeffrey N. Weiser
Summary: The study found that infection of infants with Streptococcus pneumoniae can trigger inflammatory pathways to facilitate transmission, similar to influenza virus. By activating the type I interferon response, colonization of S. pneumoniae in the upper respiratory tract increases shedding and transmission by stimulating a wide array of genes, including those involved in mucin biosynthesis. This mechanism of S. pneumoniae contagion shared with viral infection highlights the importance of the induction of IFN-I signaling in driving respiratory contagion.
Article
Microbiology
Nori Yoshioka, Hideharu Hagiya, Matsuo Deguchi, Shigeto Hamaguchi, Masanori Kagita, Isao Nishi, Yukihiro Akeda, Kazunori Tomono
Summary: The study developed a multiplex real-time PCR assay for the detection of two different combinations of carbapenemases using clinically available equipment. The assay showed high accuracy and detection efficiency, contributing to early diagnosis of carbapenemase-producing Enterobacteriaceae with diverse genetic backgrounds.
Article
Immunology
Daichi Murakami, Masamitsu Kono, Denisa Nanushaj, Fumie Kaneko, Tonia Zangari, Yasuteru Muragaki, Jeffrey N. Weiser, Muneki Hotomi
Summary: This study revealed that cigarette smoke exposure significantly promotes pneumococcal transmission in an infant mouse model by enhancing bacterial shedding from the colonized host and increasing susceptibility to colonization in new hosts. Local inflammation and mucosal changes were identified as important underlying mechanisms for transmission promotion by smoke exposure, attributable to the constituents of cigarette smoke rather than smoke itself. These findings provide the first experimental evidence of the impact of environmental factors on pneumococcal transmission and pathogenesis mechanisms.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Cell Biology
Chen-Yuan Tseng, Michael Burel, Michael Cammer, Sneh Harsh, Maria Sol Flaherty, Stefan Baumgartner, Erika A. Bach
Summary: This study reveals that germline stem cells lacking the transcription factor Chinmo have a competitive advantage and can replace the entire germline stem cell pool over time. The study also suggests that the influence of germline stem cell competition may extend beyond individual stem cell niche dynamics to population-level allelic drift and evolution.
DEVELOPMENTAL CELL
(2022)
Article
Multidisciplinary Sciences
Madeleine M. LaRue, Seth Parker, Joseph Puccini, Michael Cammer, Alec C. Kimmelman, Dafna Bar-Sagi
Summary: Tumor-associated macrophages play a role in remodeling the extracellular matrix, which affects the growth and development of tumors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Andrew S. Bray, Richard D. Smith, Andrew W. Hudson, Giovanna E. Hernandez, Taylor M. Young, Hannah E. George, Robert K. Ernst, M. Ammar Zafar
Summary: This study investigates the biological cost of colistin resistance in Klebsiella pneumoniae. It finds that while colistin resistance reduces the ability of the bacteria to colonize the gut, it enhances their survival outside the host and therefore increases their transmission between hosts.
Article
Immunology
Andrew W. Hudson, Andrew J. Barnes, Andrew S. Bray, David A. Ornelles, M. Ammar Zafar
Summary: In this study, the researchers revealed that Klebsiella pneumoniae overcomes colonization resistance in the gut by utilizing fucose metabolism, which promotes its robust colonization. It was also found that fucose metabolism enhances hypermucoviscosity, autoaggregation, and biofilm formation of K. pneumoniae. These findings provide insights into the alternative carbon source utilization and the complex relationship between metabolism and virulence in K. pneumoniae.
INFECTION AND IMMUNITY
(2022)
Article
Multidisciplinary Sciences
Yu Matsuzawa-Ishimoto, Xiaomin Yao, Akiko Koide, Beatrix M. Ueberheide, Jordan E. Axelrad, Bernardo S. Reis, Roham Parsa, Jessica A. Neil, Joseph C. Devlin, Eugene Rudensky, M. Zahidunnabi Dewan, Michael Cammer, Richard S. Blumberg, Yi Ding, Kelly Ruggles, Daniel Mucida, Shohei Koide, Ken Cadwell
Summary: Loss of Paneth cells is associated with Crohn's disease. γδ IELs promote the viability of Paneth cells by secreting API5.
Article
Biochemistry & Molecular Biology
Ting-An Yie, Cynthia A. Loomis, Johannes Nowatzky, Alireza Khodadadi-Jamayran, Ziyan Lin, Michael Cammer, Clea Barnett, Valeria Mezzano, Mark Alu, Jackson A. Novick, John S. Munger, Matthias C. Kugler
Summary: Normal lung development relies on the coordinated action of HH and PDGF signaling pathways, which are crucial for mesenchymal differentiation and proliferation. Recent studies have shown that HH is necessary for alveolar myofibroblast differentiation. In this study, we investigated the relationship between HH and PDGF signaling during postnatal lung development in mice. Our findings suggest that HH and PDGF signaling pathways intersect to support myofibroblast function during secondary alveolar septum formation.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Immunology
M. Ammar Zafar, Alicia Costa-Terryl, Taylor M. Young
Summary: The ability of Streptococcus pneumoniae to sense and respond quickly to the changing environment of the upper respiratory tract allows it to thrive as a pathogen. Two-component systems play a crucial role in this adaptation process. They have been found to promote pneumococcal colonization and virulence in the upper respiratory tract.
INFECTION AND IMMUNITY
(2023)
Article
Multidisciplinary Sciences
Qi Sun, Wendy Lee, Hai Hu, Tatsuya Ogawa, Sophie De Leon, Ioanna Katehis, Chae Ho Lim, Makoto Takeo, Michael Cammer, M. Mark Taketo, Denise L. Gay, Sarah E. Millar, Mayumi Ito
Summary: For unknown reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations, leading to hair greying in most humans and mice. Contrary to current beliefs, McSCs are not reserved in an undifferentiated state in the hair follicle niche, but rather transition between transit-amplifying and stem cell states. This finding suggests that dedifferentiation is integral to homeostatic stem cell maintenance and may provide new insights for preventing hair greying.
Article
Oncology
Christina Glytsou, Xufeng Chen, Emmanouil Zacharioudakis, Wafa Al-Santli, Hua Zhou, Bettina Nadorp, Soobeom Lee, Audrey Lasry, Zhengxi Sun, Dimitrios Papaioannou, Michael Cammer, Kun Wang, Tomasz Zal, Malgorzata Anna Zal, Bing Z. Carter, Jo Ishizawa, Raoul Tibes, Aristotelis Tsirigos, Michael Andreeff, Evripidis Gavathiotis, Iannis Aifantis
Summary: BH3 mimetics are effective in inducing cell death in various blood malignancies, including acute myeloid leukemia (AML). Loss of mitophagy modulators, such as MFN2, sensitizes AML cells to different BH3 mimetics. Targeting MFN2 can enhance the efficacy of BH3 mimetics and increase apoptosis in AML.
Article
Nanoscience & Nanotechnology
Qinqin Sun, Jia Yao, Zhijun Zhang, Juan Li, Xue Zhang, Hui Wang, Xufang Du, Min Li, Ying Zhao
Summary: In recent years, cardiac vascular disease caused by acute myocardial infarction and heart failure has led to death worldwide. To address the complications associated with existing treatments, researchers have developed a new hydrogel material for the repair of acute myocardial infarction. Experimental results show that the hydrogel can effectively restore the infarcted heart.