Article
Microbiology
Kirsi Savijoki, Henna Myllymaki, Hanna Luukinen, Lauri Paulamaki, Leena-Maija Vanha-Aho, Aleksandra Svorjova, Ilkka Miettinen, Adyary Fallarero, Teemu O. Ihalainen, Jari Yli-Kauhaluoma, Tuula A. Nyman, Mataleena Parikka
Summary: The study reveals that the nontuberculous Mycobacterium marinum ATCC 927 forms two different types of biofilms with distinct structures and persister cells. The proteomic analysis suggests subtype-dependent mechanisms conferring increased virulence and adaptive potential. The findings highlight the importance of targeting both biofilm subtypes in antimycobacterial treatment therapies.
Article
Multidisciplinary Sciences
Sudhir Sinha, Shashikant Kumar, Komal Singh, Fareha Umam, Vinita Agrawal, Amita Aggarwal, Barbara Imperiali
Summary: Styrene maleic acid lipid particles (SMALPs) were utilized to prepare and characterize membrane proteins of Mycobacterium tuberculosis (Mtb). These nanoparticles contained inner membrane protein PRA, membrane-associated proteins PstS1, LpqH and Ag85, and lipoglycan LAM. Peripheral membrane proteins Acr and PspA were excluded. Additionally, immune responses indicated that only MtM-SMALPs could induce the production of TNF-alpha.
Article
Multidisciplinary Sciences
Hao Liu, Anjie Li, Rochaix Jean-David, Zhenfeng Liu
Summary: Chloroplasts import nuclear-encoded proteins using translocon complexes in the outer and inner envelope membranes. The structure of the TOC-TIC supercomplex from Chlamydomonas reinhardtii has been determined, revealing the overall architecture and protein organization. The presence of an inositol hexaphosphate molecule and lipid molecules within the supercomplex suggests their role in stabilizing the assembly and supporting preprotein translocation.
Article
Microbiology
November Sankey, Haley Merrick, Padam Singh, Janet Rogers, Amit Reddi, Steven D. D. Hartson, Avishek Mitra
Summary: Mycobacterium tuberculosis (Mtb) is a successful pathogen that can overcome iron limitation by utilizing heme in the human host. The ESX-4 type VII secretion system (T7SS) and two specific proteins, Rv0125 and Rv1085c, play essential roles in heme uptake. Additionally, the alternative sigma factor SigM is a global regulator of core heme utilization genes. Furthermore, some mycobacterial PPE proteins have been shown to form channels in the outer mycomembrane for nutrient acquisition.
Article
Biophysics
Stefano Conti Nibali, Maria Carmela Di Rosa, Oliver Rauh, Gerhard Thiel, Simona Reina, Vito De Pinto
Summary: VDAC is a key protein of the outer mitochondrial membrane in all eukaryotes, with its electrophysiological properties extensively analyzed. A one-step reaction combining in vitro cell-free protein expression with nanodisc technology has been proposed to obtain human VDAC isoforms integrated in a native-like lipid bilayer, overcoming the limitations of membrane protein overexpression. Membrane-mimicking nanodisc systems represent a breakthrough in VDAC electrophysiology and may be utilized for further structural studies.
BIOPHYSICAL REPORTS
(2021)
Article
Nanoscience & Nanotechnology
Shanshan Guo, Fernando Cazarez-Marquez, Han Jiao, Ewout Foppen, Nikita L. Korpel, Anita E. Grootemaat, Nalan Liv, Yuanqing Gao, Nicole van der Wel, Bing Zhou, Guangjun Nie, Chun-Xia Yi
Summary: This study introduces a method using lipid and polymer hybridized nanoparticles for local delivery of small interfering RNA (siRNA) to silence specific microglial genes in the hypothalamus. The researchers demonstrated the effectiveness of this method both in vitro and in vivo, showing significant reductions in gene expression and microglial activation.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Tanzir Ahmed, Jayesh Arun Bafna, Roland Hemmler, Karsten Gall, Richard Wagner, Mathias Winterhalter, Michael J. Vellekoop, Sander van den Driesche
Summary: This work presents a microsystem setup for sensitive biological membrane translocation measurements. Thin free-standing synthetic bilayer lipid membranes (BLM) are constructed in microfabricated silicon nitride apertures and used for electrophysiological measurements of pore proteins. The integration of pore-forming proteins is achieved through direct reconstitution or reconstitution via outer membrane vesicles (OMVs) released from Gram-negative bacteria. This microsystem allows for investigation of fast gating events, pore blocking, and gating events of small pores.
Article
Chemistry, Multidisciplinary
Jiajun Wang, Jigneshkumar Dahyabhai Prajapati, Fan Gao, Yi-Lun Ying, Ulrich Kleinekathoefer, Mathias Winterhalter, Yi-Tao Long
Summary: Chirality is important but often overlooked in biological and chemical processes due to technical limitations. Researchers have used an electrostatically asymmetric membrane channel to successfully identify chiral amino acids in single peptides. This study provides a new approach for developing chiral recognition and protein sequencing methods.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Igor V. Bodrenko, Tsedenia Alemu Zewdie, Jiajun Wang, Eshita Paul, Susanne Witt, Mathias Winterhalter
Summary: This study investigates protein-protein interaction using electrophysiology, focusing on the structure of the TolC-AcrA-AcrB complex and the inhibitory effect of potential efflux pump inhibitors. The findings suggest that the fluctuation of ion current and the average current through the TolC channel can be used as complementary measures to assess the interaction of the complex.
Article
Cardiac & Cardiovascular Systems
Edgar E. Nollet, Inez Duursma, Anastasiya Rozenbaum, Moritz Eggelbusch, Rob C. Wuest, Stephan A. C. Schoonvelde, Michelle Michels, Mark Jansen, Nicole N. van der Wel, Kenneth C. Bedi, Kenneth B. Margulies Jr, Jeff Nirschl, Diederik W. D. Kuster, Jolanda van der Velden
Summary: This study found that mitochondrial dysfunction is related to pathological remodelling in hypertrophic cardiomyopathy (HCM). In patients without genetic mutations, there is a stronger association between mitochondrial dysfunction and septal hypertrophy. The study also suggests that targeting mitochondria with specific drugs can restore mitochondrial function in HCM patients.
EUROPEAN HEART JOURNAL
(2023)
Article
Chemistry, Medicinal
Ann-Britt Schafer, Maurice Steenhuis, Kin Ki Jim, Jolanda Neef, Sarah O'Keefe, Roger C. Whitehead, Eileithyia Swanton, Biwen Wang, Sven Halbedel, Stephen High, Jan Maarten van Dijl, Joen Luirink, Michaela Wenzel
Summary: Eeyarestatin 24 (ES24) is a promising new antibiotic that inhibits SecYEG-mediated protein transport in Gram-negative bacteria and has notable activity against Gram-positive bacteria. It causes DNA damage and membrane potential dissipation in Escherichia coli but not in Bacillus subtilis. ES24 differs from nitrofurantoin in its mechanism of action and outperforms it in a zebrafish embryo pneumococcal infection model, suggesting multiple targets in bacteria.
ACS INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Vien Q. T. Ho, Mark K. Rong, Eva Habjan, Samantha D. Bommer, Thang V. Pham, Sander R. Piersma, Wilbert Bitter, Eelco Ruijter, Alexander Speer
Summary: In this study, a 1,2,4-oxadiazole derivative was found to inhibit the secretion of active lipase LipY by the ESX-5 secretion system. Other ESX-5 substrates were even more abundantly secreted in the presence of several 1,2,4-oxadiazoles. These compounds significantly reduced bacterial burden in zebrafish models.
Article
Chemistry, Multidisciplinary
Yao Chen, Andrea Barba-Bon, Bohumir Gruner, Mathias Winterhalter, M. Alphan Aksoyoglu, Sushil Pangeni, Maryam Ashjari, Klaudia Brix, Giulia Salluce, Yeray Folgar-Camean, Javier Montenegro, Werner M. Nau
Summary: Cobalt bisdicarbollides (COSANs) are used as selective and efficient molecular carriers to transport hydrophilic oligopeptides through membranes. They can permeate lipid bilayer membranes without causing membrane damage. COSANs transport arginine-rich and lysine-rich peptides effectively, but cannot transport small molecules or anionic cargos. The transportation mechanism is a molecular carrier mechanism, and living cell experiments show that a fluorescent peptide cargo can be delivered into the cytosol.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Immunology
Manon Beaujean, Rienke F. Uijen, Jeroen D. Langereis, David Boccara, Denise Dam, Angele Soria, Gert Veldhuis, Lucille Adam, Olivia Bonduelle, Nicole N. Van der Wel, Joen Luirink, Eric Pedruzzi, Jeroen Wissink, Marien I. de Jonge, Behazine Combadiere
Summary: It has been shown that the use of a novel silicon microinjection needle improves the delivery of vaccines in the human skin. The new needle allows for a more precise and effective injection, resulting in higher activation of antigen-presenting cells. This study indicates the potential benefits of using microinjection needles for vaccine delivery.
Article
Oncology
Lisette Waanders, Lieve E. H. van der Donk, Louis S. Ates, Janneke Maaskant, John L. van Hamme, Eric Eldering, Jaco A. C. van Bruggen, Joanne M. Rietveld, Wilbert Bitter, Teunis B. H. Geijtenbeek, Coenraad P. Kuijl
Summary: By expressing cGAS in Salmonella typhimurium, the STING pathway can be activated in vitro, leading to enhanced cytotoxic T-cell response and tumor cell killing. This suggests the potential of Salmonella typhimurium-cGAS in vitro and provides rationale for further in vivo research.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Dung T. T. Huynh, Wouter S. P. Jong, Manon A. H. Oudejans, H. Bart van den Berg van Saparoea, Joen Luirink, Peter van Ulsen
Summary: This study explored the use of outer membrane vesicles (OMVs) as safe vaccine vectors to display immunogenic molecules, such as C. trachomatis PmpD, on the surface of E. coli and Salmonella Typhimurium OMVs. The findings suggested that optimal expression strategies for different antigens should be developed on a case-by-case basis.
Article
Multidisciplinary Sciences
Ilona van Alen, Mayra A. Aguirre Garcia, Janneke J. Maaskant, Coenraad P. Kuijl, Wilbert Bitter, Annemarie H. Meijer, Marcellus Ubbink
Summary: This study tested the activity of variants of the beta-lactamase enzyme BlaC from Mycobacterium tuberculosis under more physiological conditions and investigated their effectiveness in combination therapy with antibiotics and inhibitors using a zebrafish infection model. The results suggest that the zebrafish host is less sensitive to the combinatorial therapy, which is important for the future development of combination therapies to treat tuberculosis.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Physical
Stefan Milenkovic, Jiajun Wang, Silvia Acosta-Gutierrez, Mathias Winterhalter, Matteo Ceccarelli, Igor V. Bodrenko
Summary: Transmembrane beta-barrel proteins are versatile candidates for various technological applications and their behavior is influenced by environmental conditions. Comparing two highly homologous porins, OmpF and OmpC, we observed subtle amino acid substitutions that can modulate mass transport properties. These differences can be attributed to the disparities in the environmental conditions under which the porins are expressed. Our analysis not only highlights the advantages of enhanced sampling methods, but also provides valuable insights into the biological function and technical applications of these proteins.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Medicine, Research & Experimental
Melissa Bedard, Sanne van der Niet, Elliott M. Bernard, Gregory Babunovic, Tan-Yun Cheng, Beren Aylan, Anita E. Grootemaat, Sahadevan Raman, Laure Botella, Eri Ishikawa, Mary P. O'Sullivan, Jacob A. Mayfield, Seonadh O'Leary, Jeffrey Buter, Adriaan J. Minnaard, Sarah M. Fortune, Leon O. Murphy, Daniel S. Ory, Joseph Keane, Sho Yamasaki, Maximiliano G. Gutierrez, Nicole van der Wel, D. Branch Moody
Summary: Induction of lipid-laden foamy macrophages is a characteristic of tuberculosis (TB) and is caused by a terpenyl nucleoside shed from Mycobacterium tuberculosis. This shed nucleoside, known as 1-tuberculosinyladenosine (1-TbAd), blocks lysosomal maturation and autophagy, leading to lipid storage in M1 macrophages. Furthermore, 1-TbAd induces the storage of specific lipids and promotes the growth of M. tuberculosis, as well as mimicking the lipid storage patterns found in lysosomal storage diseases such as Gaucher's disease and Wolman's disease.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Microbiology
Anita E. Grootemaat, Niek Wiersma, Sanne van der Niet, Irene M. Schimmel, Sandrine Florquin, Eric A. Reits, Sara E. Miller, Nicole N. van der Wel
Summary: This study investigated the presence of SARS-CoV-2 viral proteins and particles in the kidneys of fatal COVID-19 patients and patients with kidney failure after recovering from SARS-CoV-2 infection. The study found accumulation of the viral nucleocapsid N protein in the kidney tubular epithelium of a patient with acute kidney failure, but no replication of the virus in the kidney.
MICROBIOLOGY SPECTRUM
(2023)
