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Studies to resolve which of the three known functions of Pfs were key to murine virulence suggested that downstream production of autoinducer-2, spermidine and methylthioribose were non-essential for Salmonella virulence in a highly sensitive murine model. Mass spectrometry revealed the accumulation of SAH in S. Typhimurium \u0394pfs and complementation of the Pfs mutant with the specific SAH hydrolase from Legionella pneumophila reduced SAH levels, fully restored growth ex vivo and the virulence of S. Typhimurium \u0394pfs for mice. The data suggest that Pfs may be a legitimate target for antimicrobial development, and that the key role of Pfs in bacterial virulence may be in reducing the toxic accumulation of SAH which, in turn, suppresses an undefined methyltransferase.<\/jats:p>","DOI":"10.1042\/bcj20190297","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T14:52:40Z","timestamp":1572619960000},"page":"3435-3453","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The multifunctional enzyme S-adenosylhomocysteine\/methylthioadenosine nucleosidase is a key metabolic enzyme in the virulence of <i>Salmonella enterica<\/i> var Typhimurium"],"prefix":"10.1042","volume":"476","author":[{"given":"Asma U.","family":"Husna","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan J.","family":"Wilksch","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-2001","authenticated-orcid":false,"given":"Hayley J.","family":"Newton","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dianna M.","family":"Hocking","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iain D.","family":"Hay","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Monash University, Clayton, Victoria 3800 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon A.","family":"Cobbold","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Parkville, Victoria 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm J.","family":"McConville","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Parkville, Victoria 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trevor","family":"Lithgow","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Monash University, Clayton, Victoria 3800 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0614-5641","authenticated-orcid":false,"given":"Richard A.","family":"Strugnell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2019,11,21]]},"reference":[{"key":"2021112218030095200_BCJ-2019-0297C1","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1038\/sj.bjp.0707432","article-title":"Novel approaches to developing new antibiotics for bacterial infections","volume":"152","year":"2007","journal-title":"Br. 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