Article
Biochemistry & Molecular Biology
Dries Smets, Alexandra Tsirigotaki, Jochem H. Smit, Srinath Krishnamurthy, Athina G. Portaliou, Anastassia Vorobieva, Wim Vranken, Spyridoula Karamanou, Anastassios Economou
Summary: This study investigates the delayed folding mechanism and the regulatory role of signal peptides in the Sec pathway. By comparing two homologous proteins, PpiA and PpiB, it is found that PpiA folds slower and the folding process involves hierarchical foldons. The folding of PpiA is delayed by less hydrophobic native contacts, frustrated residues, and a beta-turn in the earliest foldon, as well as by signal peptide-mediated disruption of foldon hierarchy. Additionally, grafting selected residues or the signal peptide of PpiA onto PpiB converts it into a slow folder with enhanced in vivo secretion. These structural adaptations facilitate protein trafficking.
Article
Immunology
Bharti Bhatia, Chadwick Hillman, Philip E. Stewart, Patricia Rosa
Summary: The highly conserved gene bba30 on the linear plasmid lp54 of Lyme disease spirochetes was found to be not required during the experimental mouse-tick infectious cycle, suggesting its potential role in the natural life cycle of Borrelia burgdorferi remains undefined.
INFECTION AND IMMUNITY
(2021)
Article
Infectious Diseases
Mariska Kerstholt, Michelle Brouwer, Marcel te Vrugt, Marije Oosting, Mihai G. Netea, Leo A. B. Joosten
Summary: This study found that the spirochete B. burgdorferi can affect the host's antioxidant capacity, reducing the ability of cells to generate ROS but resulting in an overproduction of ROS at a later stage. The PI3K/Akt pathway and intracellular levels of methionine play important roles in regulating this process. Dysregulation of oxidative metabolism may be a novel mechanism by which the spirochete modulates the human immune system and evades killing.
TICKS AND TICK-BORNE DISEASES
(2022)
Article
Multidisciplinary Sciences
Jos J. A. Trentelman, Julen Tomas-Cortazar, Sarah Knorr, Diego Barriales, Ondrej Hajdusek, Radek Sima, Jasmin Ersoz, Sukanya Narasimhan, Erol Fikrig, Ard M. Nijhof, Juan Anguita, Joppe W. Hovius
Summary: Ixodes ricinus is the most important vector of human infectious diseases in Europe, particularly Lyme borreliosis and tick-borne encephalitis virus. Research has shown that immunity developed after repeated tick bites can reduce the likelihood of contracting Lyme borreliosis in humans. While a vaccine mimicking tick immunity could potentially prevent Lyme borreliosis, the vaccination studies with selected tick salivary gland proteins did not provide protection in current form. Future efforts will focus on exploring the biological functions of these proteins and alternative systems for recombinant protein generation for vaccination.
SCIENTIFIC REPORTS
(2021)
Article
Biotechnology & Applied Microbiology
Matthew Pine, Gunjan Arora, Thomas M. Hart, Emily Bettini, Brian T. Gaudette, Hiromi Muramatsu, Istvan Tombacz, Taku Kambayashi, Ying K. Tam, Dustin Brisson, David Allman, Michela Locci, Drew Weissman, Erol Fikrig, Norbert Pardi
Summary: This study proposes the development of a Lyme disease vaccine using the mRNA-LNP platform, which induces stronger immune responses and provides protection against bacterial infection compared to traditional protein subunit vaccines.
Article
Microbiology
Lindsay C. Sidak-Loftis, Kristin L. Rosche, Natasha Pence, Jessica K. Ujczo, Joanna Hurtado, Elis A. Fisk, Alan G. Goodman, Susan M. Noh, John W. Peters, Dana K. Shaw
Summary: The study discovers a novel linkage between the unfolded-protein response (UPR) and the immune deficiency (IMD) pathway in arthropods, explaining how the IMD pathway can be activated in ticks and restrict the transmission of pathogens.
Review
Microbiology
Brian Stevenson
Summary: The Lyme disease spirochete persists in nature through cycles between ticks and vertebrates, but it has a limited ability to sense its external environment. Detailed investigations on Borrelia burgdorferi have revealed the molecular mechanisms through which it controls production of virulence-associated factors. This has led to the development of a model explaining how B. burgdorferi controls expression of its diverse proteins through changes triggered by specific physiological and metabolic states during its infectious cycle.
CURRENT OPINION IN MICROBIOLOGY
(2023)
Article
Anatomy & Morphology
Sinan Muldur, Felix Ellett, Anika L. Marand, Charles Marvil, John A. Branda, Jacob E. LeMieux, Adam B. Raff, Klemen Strle, Daniel Irimia
Summary: Human neutrophils in blood samples from both Lyme disease patients and healthy donors exhibit robust migratory responses to Borrelia burgdorferi, which are complement-dependent. Inhibition of complement factor 5 cleavage reduces neutrophil-Bb interactions and spontaneous neutrophil motility. The microfluidic assay is validated as a useful tool for studying neutrophil-Bb interactions in blood samples.
CELLS TISSUES ORGANS
(2022)
Article
Chemistry, Multidisciplinary
Qingmei Zhong, Xuedong Huang, Rongrong Zhang, Kun Zhang, Baohong Liu
Summary: Innovation in single-cell analysis has enabled accurate sensing of cell secretion events with high spatiotemporal resolution, revolutionizing the analysis of cell secretion. Optical sensing strategies allow for real-time monitoring of various substances released by single live cells, providing high-resolution analysis capabilities with accuracy.
Article
Biochemistry & Molecular Biology
Jisu Im, Tamara Hillenaar, Hui Ying Yeoh, Priyanka Sahasrabudhe, Marjolein Mijnders, Marcel van Willigen, Azib Hagos, Eduardo de Mattos, Peter van der Sluijs, Ineke Braakman
Summary: We have discovered the sequential events involved in the proper folding of the ABC transporter CFTR, a large multi-domain, multi-spanning membrane protein. Our study revealed that CFTR folds in two distinct stages: a co-translational stage involving the folding of certain domains, followed by a post-translational stage involving the assembly of these domains. We also investigated the effects of mutations on CFTR folding and found that a disease-causing mutation disrupted the first stage of folding, but not the second stage, which could be rescued by corrector drugs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jenny Wachter, Britney Cheff, Chad Hillman, Valentina Carracoi, David W. Dorward, Craig Martens, Kent Barbian, Glenn Nardone, L. Renee Olano, Margie Kinnersley, Patrick R. Secor, Patricia A. Rosa
Summary: The alternative sigma factor RpoS plays a crucial role in the critical host-adaptive response of Borrelia burgdorferi, the Lyme disease spirochete. This study characterises the negative regulator bbd18 of RpoS and demonstrates its essential nature for the viability of wild-type spirochetes in vitro and in vivo. Transcriptomic analyses reveal that BBD18 depletion leads to global induction of RpoS-dependent genes, which can be circumvented by deletion of rpoS.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Gregory B. Cole, Thomas J. Bateman, Trevor F. Moraes
Summary: The outer membrane of gram-negative pathogens provides protection from environmental insults and restricts vital nutrient entry, but surface lipoproteins (SLPs) can aid in immune evasion and nutrient acquisition. As more bacterial genomes are sequenced, the prevalence and different roles of SLPs are being discovered, offering potential as antimicrobial targets. Through understanding the structures and mechanisms of SLPs, alongside bioinformatics and genome sequencing, we may develop new therapies and vaccine antigens.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Microbiology
Thomas M. Hart, Alan P. Dupuis, Danielle M. Tufts, Anna M. Blom, Simon R. Starkey, Ryan O. M. Rego, Sanjay Ram, Peter Kraiczy, Laura D. Kramer, Maria A. Diuk-Wasser, Sergios-Orestis Kolokotronis, Yi-Pin Lin
Summary: The research identified species-level differences in bacterial transmission of Lyme disease, which are influenced by the tick blood meal, vertebrate defense mechanisms, and a polymorphic bacterial protein, CspA. The study showed that CspA enables bacterial transmission to specific vertebrates by inactivating the vertebrate complement in a species-specific manner. This species-specific complement evasion mechanism likely emerged through convergent evolution during the last glacial maximum, shaping the host-pathogen associations in Lyme disease infection.
Review
Parasitology
Zarna Rajeshkumar Pala, Medard Ernest, Brendan Sweeney, Yeong Je Jeong, Tales Vicari Pascini, Thiago Luiz Alves E. Silva, Joel Vega-Rodriguez
Summary: Plasmodium and other vector-borne pathogens have evolved mechanisms to exploit the mammalian fibrinolytic system for infection and transmission. Plasmin plays a crucial role in maintaining vascular homeostasis and degrading proteins. Understanding these mechanisms can help develop innovative strategies to prevent pathogen transmission.
TRENDS IN PARASITOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hunter W. Kuhn, George F. Aranjuez, Mollie W. Jewett
Summary: Borrelia burgdorferi, the causative agent of Lyme disease, contains a protein BBK13 with unknown function predicted to have a significant role in infection. Through analysis of structure and oligomeric formation, it is suggested that the oligomeric structure of BBK13 may be crucial for its function as a critical infection protein.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)