{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T14:35:33Z","timestamp":1761662133403},"reference-count":22,"publisher":"Microbiology Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,4,1]]},"abstract":"Mutants of Salmonella<\/jats:italic> defective in DNA adenine methylase (dam<\/jats:italic>) have been reported to be attenuated for virulence and to provide protective immunity when used as vaccine strains. To determine whether these observations could be extended to Shigella<\/jats:italic>, a dam<\/jats:italic> mutant of Shigella flexneri<\/jats:italic> 2a was characterized and examined for the role of dam<\/jats:italic> in pathogenesis. The Shigella dam<\/jats:italic> mutant showed some unique characteristics; however, it retained virulence in vivo<\/jats:italic> as well as in vitro<\/jats:italic>. The mutant invaded cultured L2 monolayer cells as efficiently as the wild-type parent, but its intracellular growth was suppressed up to 7\u2005h post-invasion. Furthermore, the invading dam<\/jats:italic> mutant formed smaller plaques in cell monolayers compared to the parent strain. However, the mutant produced keratoconjunctivitis in the Sereny test in guinea pigs only slightly more slowly than the wild-type. While the effect of the dam<\/jats:italic> mutation on virulence was modest, the rate of spontaneous mutation in the dam<\/jats:italic> mutant was 1000-fold greater compared with the wild-type. The virulence and high mutability displayed by the dam<\/jats:italic> mutant of Sh. flexneri<\/jats:italic> suggest that a general anti-bacterial pathogen vaccine strategy based on mutations in dam<\/jats:italic> needs to be re-evaluated.<\/jats:p>","DOI":"10.1099\/mic.0.26781-0","type":"journal-article","created":{"date-parts":[[2004,4,8]],"date-time":"2004-04-08T23:07:57Z","timestamp":1081465677000},"page":"1073-1078","source":"Crossref","is-referenced-by-count":12,"title":["A DNA adenine methylase mutant of Shigella flexneri shows no significant attenuation of virulence"],"prefix":"10.1099","volume":"150","author":[{"given":"Yasuko","family":"Honma","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinaldo E.","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony T.","family":"Maurelli","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, F. 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