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
Biochemistry & Molecular Biology
Liana A. A. Savintseva, Ilya S. S. Steshin, Alexander A. A. Avdoshin, Sergey V. V. Panteleev, Alexey V. V. Rozhkov, Ekaterina A. A. Shirokova, Grigory D. D. Livshits, Alexander V. V. Vasyankin, Eugene V. V. Radchenko, Stanislav K. K. Ignatov, Vladimir A. A. Palyulin
Summary: For the first time, all-atom long-term molecular dynamic simulations were used to study the conformational changes and favorable structures of mycolic acid-based membranes in Mycobacterium tuberculosis. The structure and properties of the membranes depend on the initial packing of alpha-mycolic acid (AMA) molecules and the presence of secondary membrane components. The presence of keto- and methoxy mycolic acids stabilizes certain conformations of AMA and promotes the formation of a stronger mycobacterial membrane.
Article
Chemistry, Medicinal
Hamish S. S. Sutherland, Guo-Liang Lu, Amy S. T. G. Tong, Daniel M. Conole, Scott G. U. Franzblau, Anna B. Upton, Manisha U. D. Lotlikar, Christopher B. J. Cooper, Brian D. A. Palmer, Peter J. Choi, William A. Denny
Summary: This study reports tetrahydronaphthalene amides (THNAs) as a new class of ATP synthase inhibitors that effectively inhibit the growth of Mycobacterium tuberculosis (M.tb). The design, synthesis, and structure-activity relationship studies of THNA analogues were conducted, and several compounds with potent in vitro M.tb growth inhibition were identified. Pharmacokinetic and off-target profiling studies were also performed to evaluate the potential of these THNAs as therapeutic options for TB.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Microbiology
Celine Rens, Joseph D. Chao, Danielle L. Sexton, Elitza Tocheva, Yossef Av-Gay
Summary: PDIMs are complex lipids found in the cell envelope of Mycobacterium tuberculosis that play a key role in the pathogenesis of the bacterium, particularly in bacterial virulence and in association with the ESX-1 secretion system. However, the mechanisms by which PDIMs help M. tuberculosis to control macrophage phagocytosis, inhibit phagosome acidification and modulate host innate immunity are still not fully understood.
Article
Multidisciplinary Sciences
Liangqian Huang, Trisha Agrawal, Guixin Zhu, Sixiang Yu, Liming Tao, JiaBei Lin, Ronen Marmorstein, James Shorter, Xiaolu Yang
Summary: Protein quality control systems are crucial for cellular function and organismal health. Recent studies have shown that polyD/E proteins, such as DAXX, ANP32A, and SET, may constitute a multifunctional protein quality control system that operates via a distinctive mechanism without relying on ATP.
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
Plant Sciences
Dovile Barcyte, Wenche Eikrem, Anette Engesmo, Sergio Seoane, Jens Wohlmann, Ales Horak, Tatiana Yurchenko, Marek Elias
Summary: Olisthodiscus represents a novel phylogenetically distinct ochrophyte lineage, with a plastid genome containing unique genes inherited from the rhodophyte ancestor and possessing a unique plastidial sulfate transporter SulT. Additionally, it is the only known ochrophyte with a cemA gene in its plastid genome, and phylogenetic analysis has ruled out the hypothesis of horizontal cemA transfer from a green algal plastid into Synurales.
JOURNAL OF PHYCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Wing Yin Venus Lau, Gemma R. Hoad, Vivian Jin, Geoffrey L. Winsor, Ashmeet Madyan, Kristen L. Gray, Matthew R. Laird, Raymond Lo, Fiona S. L. Brinkman
Summary: Protein subcellular localization is crucial for understanding protein function and identifying potential diagnostic markers, drug targets, and vaccine components. PSORTdb 4.0 is an updated database featuring experimentally verified and pre-computed protein localization data, with a user-friendly search function and expanded information on novel localizations. It is a valuable resource for researchers studying various microbes with diverse cell envelope structures.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Fantahun Biadglegne, Johannes R. Schmidt, Kathrin M. Engel, Joerg Lehmann, Robert T. Lehmann, Anja Reinert, Brigitte Konig, Juergen Schiller, Stefan Kalkhof, Ulrich Sack
Summary: Tuberculosis (TB) is still one of the deadliest infectious diseases caused by the bacterium Mycobacterium tuberculosis (Mtb). This study investigated the lipid and protein composition of exosomes derived from TB patients' plasma, and found that the exosomes contain components from both the host and Mtb. The proportions of these components vary depending on disease and treatment state, and may be related to Mtb pathogenesis and dormancy. The study also identified proteins of Mtb origin and revealed the impact of Mtb infection on the host protein composition of circulating exosomes. These findings could lead to the development of new vaccines and therapies for TB.
Article
Multidisciplinary Sciences
Yun Xiang, Rui Lyu, Junjie Hu
Summary: Membrane curvature is generated by constructing a curved oligomeric scaffold formed by endoplasmic reticulum tubule-forming proteins. The mechanism of curvature generation remains elusive.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Casey M. Stevens, Svitlana O. Babii, Amitkumar N. Pandya, Wei Li, Yupeng Li, Jitender Mehla, Robyn Scott, Pooja Hegde, Pavan K. Prathipati, Atanu Acharya, Jinchan Liu, James C. Gumbart, Jeffrey North, Mary Jackson, Helen I. Zgurskaya
Summary: In this study, the researchers successfully purified and reconstituted MmpL3 and CmpL1 proteins into proteoliposomes. The proteins were found to facilitate proton translocation across a phospholipid bilayer, but they differed in their pH responses and interactions with substrate mimics and inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemical Research Methods
Jaeyong Jung, Ji-Hong Bong, Jeong Soo Sung, Soo Jeong Lee, Misu Lee, Min-Jung Kang, Joachim Jose, Jae-Chul Pyun
Summary: In this study, binding domains for fluorescent dyes were identified from a Fv-antibody library prepared on the outer membrane of Escherichia coli, and the CDR3 regions of these antibodies were synthesized into peptides to analyze their binding activity to fluorescent dyes. The synthesized peptides were then co-expressed as fusion proteins with Z-domain, demonstrating their binding activity to the fluorescent dyes.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Microbiology
Sunyia Hussain, Janine H. Peterson, Harris D. Bernstein
Summary: The assembly of trimeric porins involves a stepwise process that requires the presence of the Bam complex and LPS. The interaction with LPS is not only essential for trimerization but also for the productive insertion of individual subunits into the lipid bilayer.
Review
Microbiology
Brijeshwar Singh, Surbhi Jaiswal, Prashant Kodgire
Summary: The indiscriminate use of antibiotics has led to the emergence of unmanageable antibiotic-resistant bacteria. Vibrio spp. is a gram-negative enteric pathogenic group with more than 100 species infecting humans and fish. It is divided into two groups, one causing cholera and the other causing non-cholera or vibriosis infections. Preventative measures such as vaccinations need to be developed to control Vibrio infections and reduce reliance on antibiotics, especially with the emergence of multi-drug resistant strains. This review aims to provide comprehensive information on Vibrio spp. outer membrane proteins and vesicles, including their structure, function, and immunoprotective role.
CRITICAL REVIEWS IN MICROBIOLOGY
(2023)
Article
Chemistry, Physical
Anna Puiggali-Jou, Brenda G. Molina, Maximilien Lopes-Rodrigues, Catherine Michaux, Eric A. Perpete, David Zanuy, Carlos Aleman
Summary: The hybrid free-standing biomimetic materials integrate VDAC36 beta-barrel protein into polymer nanomembranes, reducing material resistance significantly. Electrochemical impedance spectroscopy studies show that the hybrid films can act as electrochemical supercapacitors and selectively respond to molecular ions based on their charge.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Cell Biology
David Pajuelo, Norberto Gonzalez-Juarbe, Michael Niederweis
CELLULAR MICROBIOLOGY
(2020)
Article
Microbiology
Lei Zhang, R. Curtis Hendrickson, Virginia Meikle, Elliot J. Lefkowitz, Thomas R. Ioerger, Michael Niederweis
Article
Multidisciplinary Sciences
Uday Tak, Terje Dokland, Michael Niederweis
Summary: The tuberculosis necrotizing toxin (TNT) is secreted by Mycobacterium tuberculosis to kill host cells, with proteins EsxE and EsxF forming membrane-spanning hetero-oligomeric pores that are essential for TNT secretion.
NATURE COMMUNICATIONS
(2021)
Article
Biophysics
Luning Yu, Xinqi Kang, Mohammad Amin Alibakhshi, Mikhail Pavlenok, Michael Niederweis, Meni Wanunu
Summary: In this study, it was demonstrated that planar bilayers composed of poly(1,2-butadiene)-b-poly(ethylene oxide) diblock copolymer are stable and leak-free at high guanidinium chloride concentrations. These membranes facilitate straightforward insertion and functional analysis of channels such as alpha-hemolysin and MspA. Furthermore, it was shown that alpha-hemolysin channels maintain their structural integrity at 2 M guanidinium chloride concentrations using blunt DNA hairpins as molecular reporters.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Mikhail Pavlenok, Luning Yu, Dominik Herrmann, Meni Wanunu, Michael Niederweis
Summary: The study demonstrates the conversion of octameric MspA into a single-chain pore using peptide linkers. The single-chain MspA forms membrane-spanning channels and discriminates nucleotides, showing plasticity to different subunit stoichiometries. This finding is significant for optimizing MspA as a biosensor for DNA sequencing and other applications.
BIOPHYSICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
David Pajuelo, Uday Tak, Lei Zhang, Olga Danilchanka, Anna D. Tischler, Michael Niederweis
Summary: The tuberculosis necrotizing toxin (TNT) is the major cytotoxic factor of Mycobacterium tuberculosis (Mtb) in macrophages, with its secretion and trafficking requiring the coordinated action of the ESX-4, ESX-2, and ESX-1 secretion systems. These ESX systems work together to enable the entry of TNT into the cytosol of Mtb-infected macrophages, establishing new molecular roles for the previously uncharacterized ESX-2 and ESX-4 systems.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Brady L. Spencer, Uday Tak, Jessica C. Mendonca, Prescilla E. Nagao, Michael Niederweis, Kelly S. Doran
Summary: Group B Streptococcus (GBS) encodes four types of T7SS, with the most prevalent subtype being crucial for GBS meningitis progression; the secreted T7SS effector protein EsxA contributes to GBS pathogenesis by forming pores in lipid membranes, marking the first demonstration of pore-formation in Gram-positive bacteria by EsxA.
Article
Microbiology
Rebecca K. Donegan, Yibo Fu, Jacqueline Copeland, Stanzin Idga, Gabriel Brown, Owen F. Hale, Avishek Mitra, Hui Yang, Harry A. Dailey, Michael Niederweis, Paras Jain, Amit R. Reddi
Summary: This study found that Mycobacterium tuberculosis utilizes endogenous and exogenous heme differently, and targeting heme synthesis may be an effective therapeutic strategy to treat mycobacterial infections.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Virginia Meikle, Lei Zhang, Michael Niederweis
Summary: Drug-resistant Mycobacterium tuberculosis causes current tuberculosis drugs to be ineffective, and drug efflux is an important mechanism in bacterial drug resistance. This study reveals that mutants of M. tuberculosis lacking components of the MmpS4-MmpL4 and MmpS5-MmpL5 systems are more susceptible to important drugs for treatment of drug-resistant TB. The study also identifies promising targets for the development of dual-function TB drugs.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Review
Microbiology
Wiem Abidi, Lucia Torres-Sanchez, Axel Siroy, Petya Violinova Krasteva
Summary: This review provides an overview of the current mechanistic knowledge on bacterial cellulose secretion, with a focus on the structure, assembly, and cooperativity of Bcs secretion system components.
FEMS MICROBIOLOGY REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Abril Gijsbers, Vanesa Vinciauskaite, Axel Siroy, Ye Gao, Giancarlo Tria, Anjusha Mathew, Nuria Sanchez-Puig, Carmen Lopez-Iglesias, Peter J. Peters, Raimond B. G. Ravelli
Summary: ESX-1 is a crucial virulence factor of Mycobacterium tuberculosis, involved in disrupting the phagosome membrane of host cells to evade immune system defence. The study reveals the oligomerization process of ESX-1 substrate EspB and suggests its potential role as a structural element of ESX-1. Cryo-electron microscopy data shows conservation of EspB quaternary structure across slow growing species but not in fast growing M. smegmatis.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Nicholas A. Swanson, Ravi K. Lokareddy, Fenglin Li, Chun-feng Hou, Mikhail Pavlenok, Michael Niederweis, Gino Cingolani
Summary: Bacteriophages of the Podoviridae family tightly package their genomes alongside internal virion proteins called ejection proteins, which are ejected into the host envelope for genome delivery. Researchers successfully purified and characterized recombinant versions of these ejection proteins, with a protocol that can be adapted for studying similar proteins in other phages.
Article
Biochemical Research Methods
Satish Kantipudi, Daniel Harder, Sara Bonetti, Dimitrios Fotiadis, Jean-Marc Jeckelmann
Summary: Heterodimeric amino acid transporters (HATs) are protein complexes that transport amino acids and derivatives across the plasma membrane. The complex 4F2hc-LAT1, composed of 4F2hc and LAT1, is medically relevant and associated with autism and tumor progression. Using Pichia pastoris as an expression host can help screen for the best membrane transport protein-expressing clone.
METHODS AND PROTOCOLS
(2021)
Article
Biochemistry & Molecular Biology
Thomas Lemmin, David Kalbermatter, Daniel Harder, Philippe Plattet, Dimitrios Fotiadis
JOURNAL OF STRUCTURAL BIOLOGY-X
(2020)
Article
Biochemical Research Methods
Mirko Stauffer, Stephan Hirschi, Zoehre Ucurum, Daniel Harder, Ramona Schlesinger, Dimitrios Fotiadis
METHODS AND PROTOCOLS
(2020)