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The surge in opioid-related deaths, driven predominantly by fentanyl and its synthetic derivatives, has become a critical public health concern, which is particularly evident in the United States. While the situation is less severe in Europe, the European Monitoring Centre for Drugs and Drug Addiction reports a rise in drug overdose deaths, with emerging concerns about the impact of fentanyl-related molecules. Synthetic opioids, initially designed for medical use, have infiltrated illicit markets due to their low production costs and high potency, with carfentanil posing additional threats, including potential chemical weaponization. Existing overdose mitigation heavily relies on naloxone, requiring timely intervention and caregiver presence, while therapeutic prevention strategies face many access challenges. To provide an additional treatment option, we propose the use of a fentanyl-specific monoclonal antibody (mAb), as a non-opioid method of prophylaxis against fentanyl and carfentanil. This mAb shows protection from opioid effects in a pre-clinical murine model. mAbs could emerge as a versatile countermeasure in civilian and biodefense settings, offering a novel approach to combat opioid-associated mortality., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph Verdi reports financial support was provided by National Institute on Drug Abuse. Nina Papavasiliou reports financial support was provided by Helmholtz Foundation. Erec Stebbins reports financial support was provided by Helmholtz Foundation. Joseph Verdi reports a relationship with Hepione Therapeutics Inc. that includes: employment and equity or stocks. Nina Papavasiliou reports a relationship with Hepione Therapeutics Inc. that includes: equity or stocks. Erec Stebbins reports a relationship with Hepione Therapeutics Inc. that includes: board membership and equity or stocks. Yosip Kelemen reports a relationship with Hepione Therapeutics Inc. that includes: employment. Joseph Verdi reports a relationship with Panosome GmbH that includes: employment and equity or stocks. Nina Papavasiliou reports a relationship with Panosome GmbH that includes: board membership and equity or stocks. Erec Stebbins reports a relationship with Panosome GmbH that includes: board membership and equity or stocks. Anastasia Gkeka reports a relationship with Panosome GmbH that includes: employment and equity or stocks. Katharina Urban reports a relationship with Panosome GmbH that includes: employment and equity or stocks. Monica Chandra reports a relationship with Panosome GmbH that includes: employment and equity or stocks. Dennis Greiner reports a relationship with Panosome GmbH that includes: employment. Sandra Ruf reports a relationship with Panosome GmbH that includes: equity or stocks. Selina Pollich reports a relationship with Panosome GmbH that includes: employment. Joseph Verdi has patent pending to Hepione Therapeutics Inc. Nina Papavasiliou has patent pending to Hepione Therapeutics Inc. Erec Stebbins has patent pending to Hepione Therapeutics Inc. Yosip Kelemen has patent pending to Hepione Therapeutics Inc. Marco Pravetoni has patent pending to University of Minnesota. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Bacterial pathogens have evolved a sophisticated arsenal of virulence factors to modulate host cell biology. Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) use a type III protein secretion system (T3SS) to inject microbial proteins into host cells. The T3SS effector cycle inhibiting factor (Cif) produced by EPEC and EHEC is able to block host eukaryotic cell-cycle progression. We present here a crystal structure of Cif, revealing it to be a divergent member of the superfamily of enzymes including cysteine proteases and acetyltransferases that share a common catalytic triad. Mutation of these conserved active site residues abolishes the ability of Cif to block cell-cycle progression. Finally, we demonstrate that irreversible cysteine protease inhibitors do not abolish the Cif cytopathic effect, suggesting that another enzymatic activity may underlie the biological activity of this virulence factor.

A common theme in bacterial disease is the manipulation of the eukaryotic cytoskeleton by pathogenic factors. Understanding how virulence factors operate to achieve these alterations is a growing and important research effort. This review focuses on several virulence factors from the pathogen Salmonella, and considers the contributions of structural biology to our appreciation of bacterial modulation of cytoskeletal dynamics.

GreA is a 17.6 kDa protein from Escherichia coli that induces cleavage of the nascent transcript in the elongating complex of RNA polymerase, followed by release of the 3'-terminal fragment. Crystals of GreA have been obtained from polyethylene glycol 4000, 2-propanol and sodium citrate, pH 5.6 and have been propagated by a novel seeding procedure. The crystals diffract beyond 2 A resolution and belong to the orthorhombic space group P2(1)2(1)2(1), with cell dimensions a = 101.7 A, b = 42.22 A, c = 40.05 A and with one molecule in the asymmetric unit.