{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:28:12Z","timestamp":1791646092582,"version":"4.3.4"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"21","license":[{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Previous studies showed that a considerable proportion of<jats:italic>Listeria monocytogenes<\/jats:italic>isolates obtained from foods carry a premature stop codon (PMSC) mutation in<jats:italic>inlA<\/jats:italic>that leads to production of a truncated and secreted InlA. To further elucidate the role these mutations play in virulence of<jats:italic>L. monocytogenes<\/jats:italic>, we created isogenic mutants, including (i) natural isolates where an<jats:italic>inlA<\/jats:italic>PMSC was reverted to a wild-type<jats:italic>inlA<\/jats:italic>allele (without a PMSC) and (ii) natural isolates where a PMSC mutation was introduced into a wild-type<jats:italic>inlA<\/jats:italic>allele; isogenic mutant sets were constructed to represent two distinct<jats:italic>inlA<\/jats:italic>PMSC mutations. Phenotypical and transcriptional analysis data showed that<jats:italic>inlA<\/jats:italic>PMSC mutations do not have a polar effect on the downstream<jats:italic>inlB<\/jats:italic>. Isogenic and natural strains carrying an<jats:italic>inlA<\/jats:italic>PMSC showed significantly reduced invasion efficiencies in Caco-2 and HepG2 cell lines as well as reduced virulence in oral guinea pig infections. Guinea pigs were also orally infected with a natural strain carrying the most common<jats:italic>inlA<\/jats:italic>PMSC mutation (vaccinated group), followed by challenge with a fully virulent<jats:italic>L. monocytogenes<\/jats:italic>strain 15 days postvaccination to probe potentially immunizing effects of exposure to<jats:italic>L. monocytogenes<\/jats:italic>with<jats:italic>inlA<\/jats:italic>PMSC mutations. Vaccinated guinea pigs showed reduced bacterial loads in internal organs and improved weight gain postchallenge, indicating reduced severity of infections in guinea pigs exposed to natural strains with<jats:italic>inlA<\/jats:italic>PMSC mutations. Our data support that (i)<jats:italic>inlA<\/jats:italic>PMSC mutations are causally associated with attenuated virulence in mammalian hosts and (ii) naturally occurring virulence-attenuated<jats:italic>L. monocytogenes<\/jats:italic>strains commonly found in food confer protective immunity.<\/jats:p>","DOI":"10.1128\/aem.00997-08","type":"journal-article","created":{"date-parts":[[2008,9,13]],"date-time":"2008-09-13T00:44:55Z","timestamp":1221266695000},"page":"6570-6583","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":144,"title":["<i>inlA<\/i>Premature Stop Codons Are Common among<i>Listeria monocytogenes<\/i>Isolates from Foods and Yield Virulence-Attenuated Strains That Confer Protection against Fully Virulent Strains"],"prefix":"10.1128","volume":"74","author":[{"given":"K. 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