Article
Immunology
Bijaya Sharma, Julie E. McCarthy, Cecily A. Freliech, Morgen M. Clark, Linden T. Hu
Summary: Unrecognized immunodeficiency may contribute to antibiotics' failure in treating Lyme disease symptoms. The study showed that the efficacy of doxycycline was significantly lower in mice lacking adaptive immunity, especially B cells, with the most pronounced effect seen in immunodeficient C3H mice. Additionally, the addition of a single dose of ceftriaxone to doxycycline treatment effectively cleared infection in severely immunodeficient C3H mice.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Christopher B. Zinck, Prasobh Raveendran Thampy, Ryan O. M. Rego, Dustin Brisson, Nicholas H. Ogden, Maarten Voordouw
Summary: This study compared the infection prevalence and spirochete abundance of different strains of Borrelia burgdorferi in a rodent host. The results showed variations in tissue infection and spirochete load among strains, with differences observed between male and female mice. Furthermore, the study suggests that laboratory-based estimates of pathogen abundance can predict the strain composition of this tick-borne pathogen in nature.
Article
Immunology
Bryna L. Fitzgerald, Barbara Graham, Mark J. Delorey, Adoracion Pegalajar-Jurado, M. Nurul Islam, Gary P. Wormser, John N. Aucott, Alison W. Rebman, Mark J. Soloski, John T. Belisle, Claudia R. Molins
Summary: This study used metabolomics to analyze metabolic responses in patients with Post-treatment Lyme disease symptoms/syndrome (PTLDS) compared to clinically cured non-PTLDS patients. The findings revealed observable metabolic differences between PTLDS and non-PTLDS patients at multiple time points, with distinct patterns of metabolite abundance. A small number of metabolites could be used to define PTLDS versus non-PTLDS patients at specific time points, and these findings were validated in a second patient cohort. These results suggest that metabolite-based measurement can help distinguish patients with PTLDS and provide insights into the underlying biochemistry of PTLDS.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Maroun M. Sfeir, Jennifer K. Meece, Elitza S. Theel, Dane Granger, Thomas R. Fritsche, Allen C. Steere, John A. Branda
Summary: Modified two-tiered testing algorithms are acceptable alternatives for Lyme disease diagnosis. The study found that these algorithms showed higher sensitivity in patients with acute erythema migrans and comparable specificity in other types of Lyme disease patients and control subjects.
JOURNAL OF CLINICAL MICROBIOLOGY
(2022)
Article
Health Care Sciences & Services
Finja Huendersen, Stefanie Forst, Erich Kasten
Summary: The study found that patients with Lyme disease have lower quality of life and sleep, as well as cognitive impairments in attention and memory. Depressive symptoms are common among Lyme patients, and the disease is often diagnosed late.
Article
Medicine, General & Internal
Klaudia Sowula, Joanna Szaleniec, Mateusz Dworak, Maria Przeklasa, Malgorzata Maraj, Piotr Ceranowicz, Jerzy Tomik
Summary: The study aimed to evaluate the frequency of vertigo symptoms and potential labyrinth damage in patients diagnosed with Lyme disease (LD). Vertigo is often associated with labyrinth and hearing-organ damage in LD patients, and antibiotic therapy is effective in reducing otoneurological symptoms.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Robert E. Rollins, Janna Wuelbern, Florian Roettgerding, Tristan A. Nowak, Sabrina Hepner, Volker Fingerle, Gabriele Margos, Yi-Pin Lin, Peter Kraiczy, Noemie S. Becker
Summary: This study investigates the role of PFam54 proteins in Lyme borreliosis pathogenesis using Borrelia bavariensis isolates naturally lacking the entire PFam54 gene array. The results show that these isolates are more susceptible to human serum but remain infectious to mice after intradermal inoculation, suggesting the nonessential role of PFam54 in long-term infection.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Immunology
Shaghayegh Jahanbani, Paige S. Hansen, Lisa K. Blum, Effie E. Bastounis, Nitya S. Ramadoss, Mallesh Pandrala, Jessica Marie Kirschmann, Grace Sisemore Blacker, Zelda Z. Love, Irving L. Weissman, Fahimeh Nemati, Michal Caspi Tal, William H. Robinson
Summary: This study sequenced the antibody repertoire of plasmablasts in Bb-infected humans and identified their binding specificities. The researchers found that by conjugating a TLR9-agonist CpG oligo to an anti-BmpA monoclonal antibody, they were able to enhance macrophage phagocytosis of Bb.
CLINICAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Lin Jin, Bao-Gui Jiang, Yizhu Yin, Jingya Guo, Jia-Fu Jiang, Xiaopeng Qi, Gary Crispell, Shahid Karim, Wu-Chun Cao, Ren Lai
Summary: Lyme spirochetes have evolved with ticks to optimize transmission to hosts. They use tick salivary molecules (TSMs) to counteract host defenses. The study shows that LT ss R signaling plays an important role in blocking the transmission and pathogenesis of tick-borne Lyme disease spirochetes. A 15-kDa TSM protein called IpSAP from Ixodes persulcatus functions as an immunosuppressant to facilitate the transmission and infection of Lyme disease spirochetes. IpSAP interacts with LT ss R to block its activation, suppressing immunity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Infectious Diseases
Elisa Kortela, Mari Kanerva, Satu Kurkela, Jarmo Oksi, Asko Jarvinen
Summary: This study evaluated the conditions behind the symptoms in patients with suspected Lyme borreliosis (LB) referred to an infectious diseases clinic. The results showed that LB was unlikely in half of the patients, with most cases having other conditions to explain their symptoms.
CLINICAL MICROBIOLOGY AND INFECTION
(2021)
Article
Immunology
Christa D. Jackson, Kinsey A. Hilliard, Charles R. Brown
Summary: The deficiency of 12/15-lipoxygenase (12/15-LO) exacerbates ankle swelling and arthritis severity in Lyme arthritis, suggesting that 12/15-LO lipid metabolites play a crucial role in resolving inflammatory arthritis. Therapeutic treatment with lipoxin A4 (LXA(4)) can alleviate joint edema and pain in Lyme arthritis patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Sanna Avellan, Daniel Bremell
Summary: The study found that adjunctive corticosteroids do not improve or impair the outcome for patients with LNB PFP treated with doxycycline.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Paul M. Arnaboldi, Adiya S. Katseff, Mariya Sambir, Raymond J. Dattwyler
Summary: This study evaluated the efficacy of using synthetic peptides containing unique epitopes from B. burgdorferi as antigen targets in Lyme disease seroassay. The results showed that combining epitopes from different antigens significantly increased the sensitivity of the assay without compromising specificity. These findings provide a new approach to improve the laboratory diagnosis of Lyme disease.
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
Immunology
George F. Aranjuez, Amanda G. Lasseter, Mollie W. Jewett
Summary: The gene bbk13 plays a crucial role in maintaining B. burgdorferi in the enzootic cycle by promoting spirochete population expansion in the skin and impacting distal tissue colonization after tick transmission. It is necessary beyond early infection in the skin and likely contributes to host immune evasion, illustrating the complex interplay between the pathogen, vector, and host for disseminated infection.
INFECTION AND IMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Harri A. Heikkinen, Sofia M. Backlund, Hideo Iwai
Summary: Partially labeling samples with 20% 13C and 100% 15N can reduce chemical costs while maintaining structural information, especially for small proteins. The approach simplifies sample preparation and enhances the efficiency of NMR technology in backbone resonance assignments, structure determination, N15-relaxation analysis, and ligand-protein interactions.
Article
Chemistry, Multidisciplinary
Shang-Te Danny Hsu, Yun-Tzai Cloud Lee, Kornelia M. Mikula, Sofia M. Backlund, Igor Tascon, Adrian Goldman, Hideo Iwai
Summary: The topology of protein structures has a significant impact on their function and physicochemical properties, with differences between backbone cyclization and structural topology affecting protein characteristics.
FRONTIERS IN CHEMISTRY
(2021)
Article
Biochemical Research Methods
Sudeep Karki, Tommi Kajander
Summary: Synaptic adhesion molecules are crucial for neuronal network organization and synapse development. Dysfunction of these molecules is associated with cognitive disorders. A recent study reveals the structure of the mouse SALM3-PTP sigma complex, providing further insight into the role of these proteins in synaptic function.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2022)
Editorial Material
Chemistry, Multidisciplinary
Yu-Hsuan Tsai, Hideo Iwai, Klaus Pors
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemical Research Methods
Harri A. Heikkinen, A. Sesilja Aranko, Hideo Iwai
Summary: Protein trans-splicing catalyzed by split inteins is used to simplify NMR signals by segmental isotopic labeling. We designed a salt-inducible intein with lower salt concentration requirements compared to naturally occurring halo-obligate inteins. The NMR solution structure of the engineered intein showed an identical three-dimensional structure to the original one, albeit it unfolds without salts. The stabilization of the active folded conformation may involve complex interactions, including solvation energy and interactions with water, ions, co-solutes, and protein polypeptide chains.
JOURNAL OF MAGNETIC RESONANCE
(2022)
Article
Microbiology
Konstantin Kogan, Karita Haapasalo, Tommi Kotila, Robin Moore, Pekka Lappalainen, Adrian Goldman, Taru Meri
Summary: Relapsing fever and Lyme Disease are caused by borrelia bacteria, which utilize host proteins to protect themselves in the human host. By analyzing the structure of the FhbA protein from Borrelia hermsii in complex with human complement regulator factor H, the study reveals how FhbA binds factor H specifically and protects the bacteria from the immune system.
Article
Biochemistry & Molecular Biology
Hannes M. Beyer, Hideo Iwai
Summary: Inteins catalyze their removal from a host protein through protein splicing. Inteins containing a site-specific endonuclease domain can exhibit genetic mobility and act as selfish elements. Crystal structures of archaeal inteins associated with an active or inactive homing endonuclease domain demonstrate structural diversity in the associated accessory domains. Protein engineering of these accessory domains in inteins enhances DNA cleaving activity and highlights a potential strategy for inteins to avoid extinction and spread.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Andreas R. Kiessling, Sarah A. Harris, Kathleen M. Weimer, Geoffrey Wells, Adrian Goldman
Summary: Gram-negative pathogens like Burkholderia pseudomallei utilize trimeric autotransporter adhesins in their pathogenicity. We studied the structure of the membrane-proximal part of BpaC head domain and found unique features, such as composition of hydrophilic residues and the position in the protein. We suggest including this BpaC-like head domain as a separate subtype and speculate that the function may depend on its location in the structure.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yixin Liu, Orquidea De Castro Ribeiro, Outi Haapanen, Gregory B. Craven, Vivek Sharma, Stephen P. Muench, Adrian Goldman
Summary: The common mutation RET(C634R) in multiple endocrine neoplasia type 2A (MEN2A) causes ligand-independent dimerization of the RET extracellular domain (ECD), disrupting normal signaling dimer formation. The mutant RET ECD can also form complexes with canonical RET ligands, resulting in distinct structures compared to the wild-type RET ECD upon ligand binding. This structural analysis provides insights into the potential mechanism of cancer induction in MEN2A and suggests new therapeutic targets.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Alexandra O. M. Holmes, Adrian Goldman, Antreas C. Kalli
Summary: In this study, we demonstrated for the first time that membrane-integral pyrophosphatases (mPPases) form specific anionic lipid interactions at specific sites. These interactions are important for protein stability and function, and may play a crucial role in future research.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mimmu K. Hiltunen, Alex J. Timmis, Maren Thomsen, Danai S. Gkotsi, Hideo Iwai, Orquidea M. Ribeiro, Adrian Goldman, Natalia A. Riobo-Del Galdo
Summary: Deleterious mutations in the X-linked PTCHD1 gene may contribute to 1% of autism cases. The function of the PTCHD1 protein is not well understood, but it may be involved in sterol transport and Hedgehog signaling. Experimental evidence suggests that PTCHD1 has distinct cellular functions and binds cholesterol similarly to PTCH1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jessica C. Boakes, Steven. P. D. Harborne, Jessie T. S. Ngo, Christos Pliotas, Adrian Goldman
Summary: Human equilibrative nucleoside transporters are important targets for cardiovascular, cancer, and viral therapies. This study identified variants of human equilibrative nucleoside transporter isoform 1 that stabilize different states of the transporter, providing insight into its transport mechanism and gating.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Meeting Abstract
Biophysics
Alexandra O. M. Holmes, Adrian Goldman, Antreas Kalli
BIOPHYSICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Jinhu Kim, Seungjoon Kim, Hyeonho Kim, In-Wook Hwang, Sungwon Bae, Sudeep Karki, Dongwook Kim, Roberto Ogelman, Geul Bang, Jin Young Kim, Tommi Kajander, Ji Won Um, Won Chan Oh, Jaewon Ko
Summary: Balanced synaptic inhibition is crucial for brain function. MDGA1 suppresses synaptic inhibition in mammalian neurons by interacting with APP, affecting GABAergic synaptic transmission in hippocampal CA1 neurons. Down-regulation of APP specifically suppresses GABAergic transmission strength and inputs in presynaptic interneurons. Overexpression of MDGA1 impairs novel object recognition memory in mice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)