Dissecting how bacterial pathogens escape immune destruction and cause respiratory infections in humans is a work in progress. One tactic employed by microbes is to use bacterial adenylate cyclase toxins (ACTs) to disarm immune cells and disrupt cellular signaling in host cells, which facilitates the infection process. Several clinically significant pathogens, such as Bacillus anthracis and Bordetella pertussis, have ACTs that are stimulated by an activator protein in human cells. Research has shown that these bacterial ACTs have evolved distinct ways of controlling their activities, but our understanding of how the B. pertussis ACT does this is limited. In a recent study, O'Brien and colleagues provide new and exciting evidence demonstrating that the regulation of B. pertussis ACT involves conformational switching between flexible and rigid states, which is triggered upon binding the host activator protein. This study increases our knowledge of how bacterial ACTs are unique enzymes, representing a potentially novel class of drug targets that may open new pathways to combat reemerging infectious diseases.
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http://dx.doi.org/10.1371/journal.pbio.2005356 | DOI Listing |
Histol Histopathol
January 2025
Institute of Anorectal Diseases, School of Integrated Traditional Chinese and Western Medicine Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, PR China.
Slow transit constipation (STC) is a colonic motor disorder characterized by a marked delay in the movement of substances through the colon. Traditional Chinese medicine (TCM) is a treasure trove of natural compounds, which is effective in treating constipation with relatively minor side effects. Zengye decoction (ZYD), a classic herbal formula in TCM, is used for moistening the intestines and relieving constipation.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg 194223, Russia.
The approaches to correct thyroid deficiency include replacement therapy with thyroid hormones (THs), but such therapy causes a number of side effects. A possible alternative is thyroid-stimulating hormone (TSH) receptor activators, including allosteric agonists. The aim of this work was to study the effect of ethyl-2-(4-(4-(5-amino-6-(-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidin-4-yl)phenyl)--1,2,3-triazol-1-yl) acetate (TPY3m), a TSH receptor allosteric agonist developed by us, on basal and thyroliberin (TRH)-stimulated TH levels and the hypothalamic-pituitary-thyroid (HPT) axis in male rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes mellitus (T2DM).
View Article and Find Full Text PDFEur J Neurosci
January 2025
Faculty of Medicine, Collegium Medicum, Mazovian Academy in Plock, Plock, Poland.
Chronic migraine (CM) is the ultimate and most burdensome form of the transformation from episodic migraine (EM), called chronification. The mechanism behind migraine chronification is poorly known and difficult to explore as CM has the same spectrum of pathogenesis as EM and the EM-CM transition is bidirectional. Central sensitization (CS) is a key phenomenon in migraine: its mechanisms include disturbed neural plasticity, which is the ability of the nervous system to adapt to endo- and exogenous changes.
View Article and Find Full Text PDFACS Chem Biol
January 2025
Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, United States.
OaPAC, the photoactivated adenylyl cyclase from , is composed of a blue light using FAD (BLUF) domain fused to an adenylate cyclase (AC) domain. Since both the BLUF and AC domains are part of the same protein, OaPAC is a model for understanding how the ultrafast modulation of the chromophore binding pocket caused by photoexcitation results in the activation of the output domain on the μs-s time scale. In the present work, we use unnatural amino acid mutagenesis to identify specific sites in the protein that are involved in transducing the signal from the FAD binding site to the ATP binding site.
View Article and Find Full Text PDFFunction (Oxf)
January 2025
Institute for Integrative Physiology, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL. 60637, USA.
Patients with obstructive sleep apnea (OSA) experience chronic intermittent hypoxia (CIH). OSA patients and CIH-treated rodents exhibit overactive sympathetic nervous system and hypertension, mediated through hyperactive carotid body (CB) chemoreflex. Activation of olfactory receptor 78 (Olfr78) by hydrogen sulfide (H2S) is implicated in CB activation and sympathetic nerve responses to CIH, but the downstream signaling pathways remain unknown.
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