Molybdenum-independent [4Fe-4S]-Catalyzed Sulfate Assimilation Sustains Salmonella Virulence

Molybdenum-independent [4Fe-4S]-Catalyzed Sulfate Assimilation Sustains Salmonella Virulence | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Molybdenum-independent [4Fe-4S]-Catalyzed Sulfate Assimilation Sustains Salmonella Virulence Andres Vazquez-Torres, Ju-Sim Kim, Siva Uppalapati, Alyssa Margolis, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7730877/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Nontyphoidal Salmonella exploits the metabolic versatility of its 17 molybdenum cofactor (MOCO)-containing MopB family members to respire on substrates as chemically disparate as formate, nitrate, and methionine sulfoxide1-4. Here, we identify three hitherto unknown periplasmic sulfate reductases within the Salmonella MopB family. These enzymes have departed from the conventional energetics of canonical MopB molybdoenzymes to embrace roles in the biosynthetic assimilation of sulfur. The three periplasmic sulfate reductases facilitate the formation of hydrogen sulfide and [Fe-S] metalloproteins, thereby enabling Salmonella to grow in gut and viscera while defending against reactive species engendered by the phagocyte NADPH oxidase. In unprecedented fashion, the catalytic cycle of these periplasmic sulfate reductases is independent of the MOCO metal center used by archetypical MopB enzymes such as nitrate or dimethyl sulfoxide reductases, relying instead on the redox activity of the nearby [4Fe-4S] prosthetic group. The existence of orthologs of Salmonella periplasmic sulfate reductases in distant evolutionary branches suggests that [4Fe-4S]-dependent catalysis may occur across the ubiquitous MopB superfamily. Our research in Salmonella offers insights into the modular evolution of redox centers in the widespread MopB superfamily, which has significantly shaped the biogeochemistry of Earth during the last 2.5 billion years. Biological sciences/Microbiology/Bacteria/Bacterial pathogenesis Biological sciences/Microbiology/Pathogens Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Kimetalsupplementaryinformation.pdf Molybdenum-independent [4Fe-4S]-Catalyzed Sulfate Assimilation Sustains Salmonella Virulence S5.xlsx Fig. S5 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7730877","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":533908395,"identity":"ea733f0c-0f9a-4062-b9e6-7141366c3afc","order_by":0,"name":"Andres 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